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Erismodegib and Buparlisib in Treating Patients With Advanced or Metastatic Basal Cell Carcinoma
This pilot trial studies how well erismodegib and buparlisib work in treating patients withbasal cell carcinoma that has spread to other places in the body. Erismodegib and buparlisibmay stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Stanford is currently accepting patients for this trial. For more information, please contact Anne Lynn Chang at 650-721-7151 .
Lead Sponsor:
Stanford University
Collaborator: National Cancer Institute (NCI)
Stanford Investigator(s):
Intervention(s):
- Drug: buparlisib
- Drug: erismodegib
- Other: laboratory biomarker analysis
- Other: questionnaire administration
Phase:
N/A
Eligibility
Inclusion Criteria:
- Able to understand and sign informed consent
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Patients with metastatic BCC, histologic confirmation of distant BCC metastasis
- Patients with metastatic disease, target lesion must be measurable using computed
tomography (CT) or magnetic resonance imaging (MRI)
- Patients with locally advanced BCC are required to have disease that is considered
inoperable due to significant functional compromise or to have a medical
contraindication to surgery
- Patients with nevoid BCC syndrome (Gorlin syndrome) may enroll in this study but must
meet the criteria for locally advanced or metastatic disease listed above
- COHORT 2 ONLY: A Smoothened inhibitor must have been previously administered as
monotherapy
- Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
- Platelets >= 80 x10^9/L
- Hemoglobin (Hb) > 9 g/dL or values >= lower limit of normal (LLN) for site-specific
lab
- Total calcium (corrected for serum albumin) within normal limits (biphosphonate use
for malignant hypercalcemia control is not allowed)
- Magnesium >= the lower limit of normal
- Potassium within normal limits for the institution
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within normal
range (or =< 3.0 x upper limit of normal [ULN] if liver metastases are present)
- Serum bilirubin within normal range (or =< 1.5 x ULN if liver metastases are present;
or total bilirubin =< 3.0 x ULN with direct bilirubin within normal range in patients
with well-documented Gilbert Syndrome)
- Serum creatinine =< 1.5 x ULN or 24-hour clearance >= 50 mL/min
- Serum amylase =< ULN
- Serum lipase =< ULN
- Fasting plasma glucose =< 120 mg/dL (6.7 mmol/L)
- Negative serum pregnancy test within 72 hours before starting study treatment in
women with childbearing potential
- International normalized ratio (INR) =< 2
Exclusion Criteria:
- Patients who have received prior treatment with a P13K inhibitor
- Patients with a known hypersensitivity to buparlisib or to its excipients
- Patients with untreated brain metastases are excluded; however, patients with
metastatic central nervous system (CNS) tumors may participate in this trial, if the
patient is > 4 weeks from therapy completion (including radiation and/or surgery), is
clinically stable at the time of study entry and is not receiving corticosteroid
therapy
- Patients with acute or chronic liver, renal disease or pancreatitis
- Patients with baseline creatinine kinase (CK) > ULN
- Patients with the following mood disorders as judged by the Investigator or a
psychiatrist, or as a result of patient's mood assessment questionnaire:
- Medically documented history of or active major depressive episode, bipolar
disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of
suicidal attempt or ideation, or homicidal ideation (immediate risk of doing
harm to others)
- >= Common Terminology Criteria for Adverse Events (CTCAE) grade 3 anxiety
- Meets the cut-off score of >= 12 in the Patient Health Questionnaire (PHQ)-9 or
a cut-off of >= 15 in the Generalized Anxiety Disorder 7-item (GAD-7) mood
scale, respectively, or selects a positive response of "1, 2, or 3" to question
number 9 regarding potential for suicidal thoughts in the PHQ-9 (independent of
the total score of the PHQ-9)
- Patients with diarrhea >= CTCAE grade 2
- Patient has active cardiac disease including any of the following:
- Left ventricular ejection fraction (LVEF) < 50% as determined by multiple gated
acquisition (MUGA) scan or echocardiogram (ECHO)
- QTc > 450 msec on screening electrocardiogram (ECG) (using the QTcF formula)
- Angina pectoris that requires the use of anti-anginal medication
- Ventricular arrhythmias except for benign premature ventricular contractions
- Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled
with medication
- Conduction abnormality requiring a pacemaker
- Valvular disease with document compromise in cardiac function
- Symptomatic pericarditis
- Patient has a history of cardiac dysfunction including any of the following:
- Myocardial infraction within the last 6 months, documented by persistent
elevated cardiac enzymes or persistent regional wall abnormalities on assessment
of LVEF function
- History of documented congestive heart failure (New York Heart Association
functional classification III-IV)
- Documented cardiomyopathy
- Patient has poorly controlled diabetes mellitus (defined as hemoglobin A1C [HgA1c] >
ULN), steroid-induced diabetes mellitus or insulin dependent diabetes mellitus
- Other concurrent severe and/or uncontrolled concomitant medical conditions (eg,
active or uncontrolled infection) that could cause unacceptable safety risks or
compromise compliance with the protocol
- Significant symptomatic deterioration of lung function; if clinically indicated,
pulmonary function tests including measures of predicted lung volumes, diffusing
capacity of the lung for carbon monoxide (DLco), oxygen (O2) saturation at rest on
room air should be considered to exclude pneumonitis or pulmonary infiltrates
- Impairment of gastrointestinal (GI) function or GI disease that may significantly
alter the absorption of buparlisib (eg, ulcerative diseases, uncontrolled nausea,
vomiting, diarrhea, malabsorption syndrome, or small bowel resection); patients with
unresolved diarrhea will be excluded as previously indicated
- Patients who have been treated with any hematopoietic colony-stimulating growth
factors (eg, granulocyte-colony stimulating factor [G-CSF], granulocyte-macrophage
colony-stimulating factor [GM-CSF]) =< 2 weeks prior to starting study drug;
erythropoietin or darbepoetin therapy, if initiated at least 2 weeks prior to
enrollment, may be continued
- Patients who are currently receiving treatment with medication with a known risk to
prolong the QT interval or inducing Torsades de Pointes and the treatment cannot
either be discontinued or switched to a different medication prior to starting study
drug
- Patients receiving chronic treatment with steroids or another immunosuppressive agent
- Note: topical applications (eg, rash), inhaled sprays (eg, obstructive airways
diseases), eye drops or local injections (eg, intr-articular) are allowed;
patients with previously treated brain metastases, who are on stable low dose
corticosteriods treatment (eg, dexamethasone 2 mg/day, prednisolone 10 mg/day)
for at least 14 days before start of study treatment are eligible
- Patients who have taken herbal medications and certain fruits within 7 days prior to
starting study drug; herbal medications include, but are not limited to St. John's
Wort, Kava, ephedra (ma huang), dehydroepiandrosterone (DHEA), gingko biloba,
yohimbe, saw palmetto, and ginseng; fruits include the cytochrome P450, family 3,
subfamily A (CYP3A) inhibitors Seville oranges, grapefruit, pummelos, or exotic
citrus fruits
- Patients who are currently treated with drugs known to be moderate and strong
inhibitors or inducers of isoenzyme CYP3A, and the treatment cannot be discontinued
or switched to a different medication prior to starting study drug; please note that
co-treatment with weak inhibitors of CYP3A is allowed
- Patients who have received chemotherapy or targeted anticancer therapy =< 4 weeks (6
weeks for nitrosourea, antibodies or mitomycin-C) prior to starting study drug must
recover to a grade 1 before starting the trial
- Patients who have received any continuous or intermittent small molecule therapeutics
(excluding monoclonal antibodies) =< 5 effective half lives prior to starting study
drug or who have not recovered from side effects of such therapy
- Use of statin drugs or other medications known to associate with rhabdomyolysis;
these drugs must be discontinued at enrollment
- Patients who have received wide field radiotherapy =< 4 weeks or limited field
radiation for palliation =< 2 weeks prior to starting study drug or who have not
recovered from side effects of such therapy
- Patients who have undergone major surgery =< 2 weeks prior to starting study drug or
who have not recovered from side effects of such therapy
- Patients who are currently taking therapeutic doses of warfarin sodium or any other
coumadin-derivative anticoagulant; low molecular weight heparin is allowed
- Women who are pregnant or breast feeding or adults of reproductive potential not
employing an effective method of birth control; double barrier contraceptives must be
used through the trial by both sexes; oral, implantable, or injectable contraceptives
may be affected by cytochrome P450 interactions, and are therefore not considered
effective for this study; women of child-bearing potential, defined as sexually
mature women who have not undergone a hysterectomy or who have not been naturally
postmenopausal for at least 12 consecutive months (ie, who has had menses any time in
the preceding 12 consecutive months), must have a negative serum pregnancy test =< 72
hours prior to initiating treatment
- Women are considered post-menopausal and not of child bearing potential if they
have had 12 months of natural (spontaneous) amenorrhea with an appropriate
clinical profile (eg, age appropriate, history of vasomotor symptoms) or six
months of spontaneous amenorrhea with serum follicle stimulating hormone (FSH)
levels > 40 mIU/mL (for US only: and estradiol < 20 pg/mL) or have had surgical
bilateral oophorectomy (with or without hysterectomy) at least six weeks ago; in
the case of oophorectomy alone, only when the reproductive status of the woman
has been confirmed by follow up hormone level assessment is she considered not
of child bearing potential
- Women of child-bearing potential, defined as all women physiologically capable
of becoming pregnant, must use highly effective contraception during the study
and through 20 months after the final dose of study treatment; for males with
partners with childbearing potential, highly effective contraception is required
for 6 months; the highly effective contraception is defined as either:
- True abstinence: when this is in line with the preferred and usual
lifestyle of the subject; periodic abstinence (eg, calendar, ovulation,
symptothermal, post-ovulation methods) and withdrawal are not acceptable
methods of contraception
- Sterilization: have had surgical bilateral oophorectomy (with or without
hysterectomy) or tubal ligation at least six weeks ago; in case of
oophorectomy alone, only when the reproductive status of the woman has been
confirmed by follow up hormone level assessment
- Male partner sterilization (with the appropriate post-vasectomy
documentation of the absence of sperm in the ejaculate); for female
subjects on the study, the vasectomized male partner should be the sole
partner for that patient
- Use of a combination of any two of the following (a+b):
- a. Placement of an intrauterine device (IUD) or intrauterine system
(IUS)
- b. Barrier methods of contraception: condom or occlusive cap
(diaphragm or cervical/vault caps) with spermicidal
foam/gel/film/cream/vaginal suppository
- Oral contraception, injected or implanted hormonal methods are not allowed
- Fertile males, must use highly effective (double barrier) methods of
contraception (eg, spermicidal gel plus condom) for the entire duration of the
study, and continuing using contraception and refrain from fathering a child for
6 months following the study drug; a condom is required to be used also by
vasectomized men as well as during intercourse with a male partner in order to
prevent delivery of the study treatment via seminal fluid; female partner of
male study subject should use highly effective contraception during dosing of
any study agent and for 16 weeks after final dose of study therapy
- Note: hormonal contraception methods (eg, oral, injected, implanted) are not
allowed
- Note: woman are considered post-menopausal and not child bearing potential if
they have had 12 months of natural (spontaneous) amenorrhea with an appropriate
clinical profile (eg, age appropriate, history of vasomotor symptoms) or six
months of spontaneous amenorrhea with serum FSH levels > 40 mIU/mL and estradiol
< 20 pg/mL or have had surgical bilateral oophorectomy (with or without
hysterectomy) at least six weeks ago; in the case of oophorectomy alone, only
when the reproductive status of the woman has been confirmed by follow up
hormone level assessment is she considered not of child bearing potential
- Known diagnosis of human immunodeficiency virus (HIV) infection, hepatitis B or
hepatitis C
- History of another malignancy within 3 years, except cured basal cell carcinoma of
the skin or excised carcinoma in situ of the cervix
- Patient is unable or unwilling to abide by the study protocol or cooperate fully with
the investigator
Ages Eligible for Study
18 Years - N/A
Genders Eligible for Study
Both
Now accepting new patients
Contact Information
Primary Contact:
Anne Lynn Chang
650-721-7151
Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Erismodegib and Buparlisib in Treating Patients With Advanced or Metastatic Basal Cell Carcinoma
This pilot trial studies how well erismodegib and buparlisib work in treating patients withbasal cell carcinoma that has spread to other places in the body. Erismodegib and buparlisibmay stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Stanford is currently accepting patients for this trial. For more information, please contact Anne Lynn Chang at 650-721-7151 .
Lead Sponsor:
Stanford University
Collaborator: National Cancer Institute (NCI)
Stanford Investigator(s):
Intervention(s):
- Drug: buparlisib
- Drug: erismodegib
- Other: laboratory biomarker analysis
- Other: questionnaire administration
Phase:
N/A
Eligibility
Inclusion Criteria:
- Able to understand and sign informed consent
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Patients with metastatic BCC, histologic confirmation of distant BCC metastasis
- Patients with metastatic disease, target lesion must be measurable using computed
tomography (CT) or magnetic resonance imaging (MRI)
- Patients with locally advanced BCC are required to have disease that is considered
inoperable due to significant functional compromise or to have a medical
contraindication to surgery
- Patients with nevoid BCC syndrome (Gorlin syndrome) may enroll in this study but must
meet the criteria for locally advanced or metastatic disease listed above
- COHORT 2 ONLY: A Smoothened inhibitor must have been previously administered as
monotherapy
- Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
- Platelets >= 80 x10^9/L
- Hemoglobin (Hb) > 9 g/dL or values >= lower limit of normal (LLN) for site-specific
lab
- Total calcium (corrected for serum albumin) within normal limits (biphosphonate use
for malignant hypercalcemia control is not allowed)
- Magnesium >= the lower limit of normal
- Potassium within normal limits for the institution
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within normal
range (or =< 3.0 x upper limit of normal [ULN] if liver metastases are present)
- Serum bilirubin within normal range (or =< 1.5 x ULN if liver metastases are present;
or total bilirubin =< 3.0 x ULN with direct bilirubin within normal range in patients
with well-documented Gilbert Syndrome)
- Serum creatinine =< 1.5 x ULN or 24-hour clearance >= 50 mL/min
- Serum amylase =< ULN
- Serum lipase =< ULN
- Fasting plasma glucose =< 120 mg/dL (6.7 mmol/L)
- Negative serum pregnancy test within 72 hours before starting study treatment in
women with childbearing potential
- International normalized ratio (INR) =< 2
Exclusion Criteria:
- Patients who have received prior treatment with a P13K inhibitor
- Patients with a known hypersensitivity to buparlisib or to its excipients
- Patients with untreated brain metastases are excluded; however, patients with
metastatic central nervous system (CNS) tumors may participate in this trial, if the
patient is > 4 weeks from therapy completion (including radiation and/or surgery), is
clinically stable at the time of study entry and is not receiving corticosteroid
therapy
- Patients with acute or chronic liver, renal disease or pancreatitis
- Patients with baseline creatinine kinase (CK) > ULN
- Patients with the following mood disorders as judged by the Investigator or a
psychiatrist, or as a result of patient's mood assessment questionnaire:
- Medically documented history of or active major depressive episode, bipolar
disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of
suicidal attempt or ideation, or homicidal ideation (immediate risk of doing
harm to others)
- >= Common Terminology Criteria for Adverse Events (CTCAE) grade 3 anxiety
- Meets the cut-off score of >= 12 in the Patient Health Questionnaire (PHQ)-9 or
a cut-off of >= 15 in the Generalized Anxiety Disorder 7-item (GAD-7) mood
scale, respectively, or selects a positive response of "1, 2, or 3" to question
number 9 regarding potential for suicidal thoughts in the PHQ-9 (independent of
the total score of the PHQ-9)
- Patients with diarrhea >= CTCAE grade 2
- Patient has active cardiac disease including any of the following:
- Left ventricular ejection fraction (LVEF) < 50% as determined by multiple gated
acquisition (MUGA) scan or echocardiogram (ECHO)
- QTc > 450 msec on screening electrocardiogram (ECG) (using the QTcF formula)
- Angina pectoris that requires the use of anti-anginal medication
- Ventricular arrhythmias except for benign premature ventricular contractions
- Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled
with medication
- Conduction abnormality requiring a pacemaker
- Valvular disease with document compromise in cardiac function
- Symptomatic pericarditis
- Patient has a history of cardiac dysfunction including any of the following:
- Myocardial infraction within the last 6 months, documented by persistent
elevated cardiac enzymes or persistent regional wall abnormalities on assessment
of LVEF function
- History of documented congestive heart failure (New York Heart Association
functional classification III-IV)
- Documented cardiomyopathy
- Patient has poorly controlled diabetes mellitus (defined as hemoglobin A1C [HgA1c] >
ULN), steroid-induced diabetes mellitus or insulin dependent diabetes mellitus
- Other concurrent severe and/or uncontrolled concomitant medical conditions (eg,
active or uncontrolled infection) that could cause unacceptable safety risks or
compromise compliance with the protocol
- Significant symptomatic deterioration of lung function; if clinically indicated,
pulmonary function tests including measures of predicted lung volumes, diffusing
capacity of the lung for carbon monoxide (DLco), oxygen (O2) saturation at rest on
room air should be considered to exclude pneumonitis or pulmonary infiltrates
- Impairment of gastrointestinal (GI) function or GI disease that may significantly
alter the absorption of buparlisib (eg, ulcerative diseases, uncontrolled nausea,
vomiting, diarrhea, malabsorption syndrome, or small bowel resection); patients with
unresolved diarrhea will be excluded as previously indicated
- Patients who have been treated with any hematopoietic colony-stimulating growth
factors (eg, granulocyte-colony stimulating factor [G-CSF], granulocyte-macrophage
colony-stimulating factor [GM-CSF]) =< 2 weeks prior to starting study drug;
erythropoietin or darbepoetin therapy, if initiated at least 2 weeks prior to
enrollment, may be continued
- Patients who are currently receiving treatment with medication with a known risk to
prolong the QT interval or inducing Torsades de Pointes and the treatment cannot
either be discontinued or switched to a different medication prior to starting study
drug
- Patients receiving chronic treatment with steroids or another immunosuppressive agent
- Note: topical applications (eg, rash), inhaled sprays (eg, obstructive airways
diseases), eye drops or local injections (eg, intr-articular) are allowed;
patients with previously treated brain metastases, who are on stable low dose
corticosteriods treatment (eg, dexamethasone 2 mg/day, prednisolone 10 mg/day)
for at least 14 days before start of study treatment are eligible
- Patients who have taken herbal medications and certain fruits within 7 days prior to
starting study drug; herbal medications include, but are not limited to St. John's
Wort, Kava, ephedra (ma huang), dehydroepiandrosterone (DHEA), gingko biloba,
yohimbe, saw palmetto, and ginseng; fruits include the cytochrome P450, family 3,
subfamily A (CYP3A) inhibitors Seville oranges, grapefruit, pummelos, or exotic
citrus fruits
- Patients who are currently treated with drugs known to be moderate and strong
inhibitors or inducers of isoenzyme CYP3A, and the treatment cannot be discontinued
or switched to a different medication prior to starting study drug; please note that
co-treatment with weak inhibitors of CYP3A is allowed
- Patients who have received chemotherapy or targeted anticancer therapy =< 4 weeks (6
weeks for nitrosourea, antibodies or mitomycin-C) prior to starting study drug must
recover to a grade 1 before starting the trial
- Patients who have received any continuous or intermittent small molecule therapeutics
(excluding monoclonal antibodies) =< 5 effective half lives prior to starting study
drug or who have not recovered from side effects of such therapy
- Use of statin drugs or other medications known to associate with rhabdomyolysis;
these drugs must be discontinued at enrollment
- Patients who have received wide field radiotherapy =< 4 weeks or limited field
radiation for palliation =< 2 weeks prior to starting study drug or who have not
recovered from side effects of such therapy
- Patients who have undergone major surgery =< 2 weeks prior to starting study drug or
who have not recovered from side effects of such therapy
- Patients who are currently taking therapeutic doses of warfarin sodium or any other
coumadin-derivative anticoagulant; low molecular weight heparin is allowed
- Women who are pregnant or breast feeding or adults of reproductive potential not
employing an effective method of birth control; double barrier contraceptives must be
used through the trial by both sexes; oral, implantable, or injectable contraceptives
may be affected by cytochrome P450 interactions, and are therefore not considered
effective for this study; women of child-bearing potential, defined as sexually
mature women who have not undergone a hysterectomy or who have not been naturally
postmenopausal for at least 12 consecutive months (ie, who has had menses any time in
the preceding 12 consecutive months), must have a negative serum pregnancy test =< 72
hours prior to initiating treatment
- Women are considered post-menopausal and not of child bearing potential if they
have had 12 months of natural (spontaneous) amenorrhea with an appropriate
clinical profile (eg, age appropriate, history of vasomotor symptoms) or six
months of spontaneous amenorrhea with serum follicle stimulating hormone (FSH)
levels > 40 mIU/mL (for US only: and estradiol < 20 pg/mL) or have had surgical
bilateral oophorectomy (with or without hysterectomy) at least six weeks ago; in
the case of oophorectomy alone, only when the reproductive status of the woman
has been confirmed by follow up hormone level assessment is she considered not
of child bearing potential
- Women of child-bearing potential, defined as all women physiologically capable
of becoming pregnant, must use highly effective contraception during the study
and through 20 months after the final dose of study treatment; for males with
partners with childbearing potential, highly effective contraception is required
for 6 months; the highly effective contraception is defined as either:
- True abstinence: when this is in line with the preferred and usual
lifestyle of the subject; periodic abstinence (eg, calendar, ovulation,
symptothermal, post-ovulation methods) and withdrawal are not acceptable
methods of contraception
- Sterilization: have had surgical bilateral oophorectomy (with or without
hysterectomy) or tubal ligation at least six weeks ago; in case of
oophorectomy alone, only when the reproductive status of the woman has been
confirmed by follow up hormone level assessment
- Male partner sterilization (with the appropriate post-vasectomy
documentation of the absence of sperm in the ejaculate); for female
subjects on the study, the vasectomized male partner should be the sole
partner for that patient
- Use of a combination of any two of the following (a+b):
- a. Placement of an intrauterine device (IUD) or intrauterine system
(IUS)
- b. Barrier methods of contraception: condom or occlusive cap
(diaphragm or cervical/vault caps) with spermicidal
foam/gel/film/cream/vaginal suppository
- Oral contraception, injected or implanted hormonal methods are not allowed
- Fertile males, must use highly effective (double barrier) methods of
contraception (eg, spermicidal gel plus condom) for the entire duration of the
study, and continuing using contraception and refrain from fathering a child for
6 months following the study drug; a condom is required to be used also by
vasectomized men as well as during intercourse with a male partner in order to
prevent delivery of the study treatment via seminal fluid; female partner of
male study subject should use highly effective contraception during dosing of
any study agent and for 16 weeks after final dose of study therapy
- Note: hormonal contraception methods (eg, oral, injected, implanted) are not
allowed
- Note: woman are considered post-menopausal and not child bearing potential if
they have had 12 months of natural (spontaneous) amenorrhea with an appropriate
clinical profile (eg, age appropriate, history of vasomotor symptoms) or six
months of spontaneous amenorrhea with serum FSH levels > 40 mIU/mL and estradiol
< 20 pg/mL or have had surgical bilateral oophorectomy (with or without
hysterectomy) at least six weeks ago; in the case of oophorectomy alone, only
when the reproductive status of the woman has been confirmed by follow up
hormone level assessment is she considered not of child bearing potential
- Known diagnosis of human immunodeficiency virus (HIV) infection, hepatitis B or
hepatitis C
- History of another malignancy within 3 years, except cured basal cell carcinoma of
the skin or excised carcinoma in situ of the cervix
- Patient is unable or unwilling to abide by the study protocol or cooperate fully with
the investigator
Ages Eligible for Study
18 Years - N/A
Genders Eligible for Study
Both
Now accepting new patients
Contact Information
Primary Contact:
Anne Lynn Chang
650-721-7151
Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Erismodegib and Buparlisib in Treating Patients With Advanced or Metastatic Basal Cell Carcinoma
This pilot trial studies how well erismodegib and buparlisib work in treating patients withbasal cell carcinoma that has spread to other places in the body. Erismodegib and buparlisibmay stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Stanford is currently accepting patients for this trial. For more information, please contact Anne Lynn Chang at 650-721-7151 .
Lead Sponsor:
Stanford University
Collaborator: National Cancer Institute (NCI)
Stanford Investigator(s):
Intervention(s):
- Drug: buparlisib
- Drug: erismodegib
- Other: laboratory biomarker analysis
- Other: questionnaire administration
Phase:
N/A
Eligibility
Inclusion Criteria:
- Able to understand and sign informed consent
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Patients with metastatic BCC, histologic confirmation of distant BCC metastasis
- Patients with metastatic disease, target lesion must be measurable using computed
tomography (CT) or magnetic resonance imaging (MRI)
- Patients with locally advanced BCC are required to have disease that is considered
inoperable due to significant functional compromise or to have a medical
contraindication to surgery
- Patients with nevoid BCC syndrome (Gorlin syndrome) may enroll in this study but must
meet the criteria for locally advanced or metastatic disease listed above
- COHORT 2 ONLY: A Smoothened inhibitor must have been previously administered as
monotherapy
- Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
- Platelets >= 80 x10^9/L
- Hemoglobin (Hb) > 9 g/dL or values >= lower limit of normal (LLN) for site-specific
lab
- Total calcium (corrected for serum albumin) within normal limits (biphosphonate use
for malignant hypercalcemia control is not allowed)
- Magnesium >= the lower limit of normal
- Potassium within normal limits for the institution
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within normal
range (or =< 3.0 x upper limit of normal [ULN] if liver metastases are present)
- Serum bilirubin within normal range (or =< 1.5 x ULN if liver metastases are present;
or total bilirubin =< 3.0 x ULN with direct bilirubin within normal range in patients
with well-documented Gilbert Syndrome)
- Serum creatinine =< 1.5 x ULN or 24-hour clearance >= 50 mL/min
- Serum amylase =< ULN
- Serum lipase =< ULN
- Fasting plasma glucose =< 120 mg/dL (6.7 mmol/L)
- Negative serum pregnancy test within 72 hours before starting study treatment in
women with childbearing potential
- International normalized ratio (INR) =< 2
Exclusion Criteria:
- Patients who have received prior treatment with a P13K inhibitor
- Patients with a known hypersensitivity to buparlisib or to its excipients
- Patients with untreated brain metastases are excluded; however, patients with
metastatic central nervous system (CNS) tumors may participate in this trial, if the
patient is > 4 weeks from therapy completion (including radiation and/or surgery), is
clinically stable at the time of study entry and is not receiving corticosteroid
therapy
- Patients with acute or chronic liver, renal disease or pancreatitis
- Patients with baseline creatinine kinase (CK) > ULN
- Patients with the following mood disorders as judged by the Investigator or a
psychiatrist, or as a result of patient's mood assessment questionnaire:
- Medically documented history of or active major depressive episode, bipolar
disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of
suicidal attempt or ideation, or homicidal ideation (immediate risk of doing
harm to others)
- >= Common Terminology Criteria for Adverse Events (CTCAE) grade 3 anxiety
- Meets the cut-off score of >= 12 in the Patient Health Questionnaire (PHQ)-9 or
a cut-off of >= 15 in the Generalized Anxiety Disorder 7-item (GAD-7) mood
scale, respectively, or selects a positive response of "1, 2, or 3" to question
number 9 regarding potential for suicidal thoughts in the PHQ-9 (independent of
the total score of the PHQ-9)
- Patients with diarrhea >= CTCAE grade 2
- Patient has active cardiac disease including any of the following:
- Left ventricular ejection fraction (LVEF) < 50% as determined by multiple gated
acquisition (MUGA) scan or echocardiogram (ECHO)
- QTc > 450 msec on screening electrocardiogram (ECG) (using the QTcF formula)
- Angina pectoris that requires the use of anti-anginal medication
- Ventricular arrhythmias except for benign premature ventricular contractions
- Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled
with medication
- Conduction abnormality requiring a pacemaker
- Valvular disease with document compromise in cardiac function
- Symptomatic pericarditis
- Patient has a history of cardiac dysfunction including any of the following:
- Myocardial infraction within the last 6 months, documented by persistent
elevated cardiac enzymes or persistent regional wall abnormalities on assessment
of LVEF function
- History of documented congestive heart failure (New York Heart Association
functional classification III-IV)
- Documented cardiomyopathy
- Patient has poorly controlled diabetes mellitus (defined as hemoglobin A1C [HgA1c] >
ULN), steroid-induced diabetes mellitus or insulin dependent diabetes mellitus
- Other concurrent severe and/or uncontrolled concomitant medical conditions (eg,
active or uncontrolled infection) that could cause unacceptable safety risks or
compromise compliance with the protocol
- Significant symptomatic deterioration of lung function; if clinically indicated,
pulmonary function tests including measures of predicted lung volumes, diffusing
capacity of the lung for carbon monoxide (DLco), oxygen (O2) saturation at rest on
room air should be considered to exclude pneumonitis or pulmonary infiltrates
- Impairment of gastrointestinal (GI) function or GI disease that may significantly
alter the absorption of buparlisib (eg, ulcerative diseases, uncontrolled nausea,
vomiting, diarrhea, malabsorption syndrome, or small bowel resection); patients with
unresolved diarrhea will be excluded as previously indicated
- Patients who have been treated with any hematopoietic colony-stimulating growth
factors (eg, granulocyte-colony stimulating factor [G-CSF], granulocyte-macrophage
colony-stimulating factor [GM-CSF]) =< 2 weeks prior to starting study drug;
erythropoietin or darbepoetin therapy, if initiated at least 2 weeks prior to
enrollment, may be continued
- Patients who are currently receiving treatment with medication with a known risk to
prolong the QT interval or inducing Torsades de Pointes and the treatment cannot
either be discontinued or switched to a different medication prior to starting study
drug
- Patients receiving chronic treatment with steroids or another immunosuppressive agent
- Note: topical applications (eg, rash), inhaled sprays (eg, obstructive airways
diseases), eye drops or local injections (eg, intr-articular) are allowed;
patients with previously treated brain metastases, who are on stable low dose
corticosteriods treatment (eg, dexamethasone 2 mg/day, prednisolone 10 mg/day)
for at least 14 days before start of study treatment are eligible
- Patients who have taken herbal medications and certain fruits within 7 days prior to
starting study drug; herbal medications include, but are not limited to St. John's
Wort, Kava, ephedra (ma huang), dehydroepiandrosterone (DHEA), gingko biloba,
yohimbe, saw palmetto, and ginseng; fruits include the cytochrome P450, family 3,
subfamily A (CYP3A) inhibitors Seville oranges, grapefruit, pummelos, or exotic
citrus fruits
- Patients who are currently treated with drugs known to be moderate and strong
inhibitors or inducers of isoenzyme CYP3A, and the treatment cannot be discontinued
or switched to a different medication prior to starting study drug; please note that
co-treatment with weak inhibitors of CYP3A is allowed
- Patients who have received chemotherapy or targeted anticancer therapy =< 4 weeks (6
weeks for nitrosourea, antibodies or mitomycin-C) prior to starting study drug must
recover to a grade 1 before starting the trial
- Patients who have received any continuous or intermittent small molecule therapeutics
(excluding monoclonal antibodies) =< 5 effective half lives prior to starting study
drug or who have not recovered from side effects of such therapy
- Use of statin drugs or other medications known to associate with rhabdomyolysis;
these drugs must be discontinued at enrollment
- Patients who have received wide field radiotherapy =< 4 weeks or limited field
radiation for palliation =< 2 weeks prior to starting study drug or who have not
recovered from side effects of such therapy
- Patients who have undergone major surgery =< 2 weeks prior to starting study drug or
who have not recovered from side effects of such therapy
- Patients who are currently taking therapeutic doses of warfarin sodium or any other
coumadin-derivative anticoagulant; low molecular weight heparin is allowed
- Women who are pregnant or breast feeding or adults of reproductive potential not
employing an effective method of birth control; double barrier contraceptives must be
used through the trial by both sexes; oral, implantable, or injectable contraceptives
may be affected by cytochrome P450 interactions, and are therefore not considered
effective for this study; women of child-bearing potential, defined as sexually
mature women who have not undergone a hysterectomy or who have not been naturally
postmenopausal for at least 12 consecutive months (ie, who has had menses any time in
the preceding 12 consecutive months), must have a negative serum pregnancy test =< 72
hours prior to initiating treatment
- Women are considered post-menopausal and not of child bearing potential if they
have had 12 months of natural (spontaneous) amenorrhea with an appropriate
clinical profile (eg, age appropriate, history of vasomotor symptoms) or six
months of spontaneous amenorrhea with serum follicle stimulating hormone (FSH)
levels > 40 mIU/mL (for US only: and estradiol < 20 pg/mL) or have had surgical
bilateral oophorectomy (with or without hysterectomy) at least six weeks ago; in
the case of oophorectomy alone, only when the reproductive status of the woman
has been confirmed by follow up hormone level assessment is she considered not
of child bearing potential
- Women of child-bearing potential, defined as all women physiologically capable
of becoming pregnant, must use highly effective contraception during the study
and through 20 months after the final dose of study treatment; for males with
partners with childbearing potential, highly effective contraception is required
for 6 months; the highly effective contraception is defined as either:
- True abstinence: when this is in line with the preferred and usual
lifestyle of the subject; periodic abstinence (eg, calendar, ovulation,
symptothermal, post-ovulation methods) and withdrawal are not acceptable
methods of contraception
- Sterilization: have had surgical bilateral oophorectomy (with or without
hysterectomy) or tubal ligation at least six weeks ago; in case of
oophorectomy alone, only when the reproductive status of the woman has been
confirmed by follow up hormone level assessment
- Male partner sterilization (with the appropriate post-vasectomy
documentation of the absence of sperm in the ejaculate); for female
subjects on the study, the vasectomized male partner should be the sole
partner for that patient
- Use of a combination of any two of the following (a+b):
- a. Placement of an intrauterine device (IUD) or intrauterine system
(IUS)
- b. Barrier methods of contraception: condom or occlusive cap
(diaphragm or cervical/vault caps) with spermicidal
foam/gel/film/cream/vaginal suppository
- Oral contraception, injected or implanted hormonal methods are not allowed
- Fertile males, must use highly effective (double barrier) methods of
contraception (eg, spermicidal gel plus condom) for the entire duration of the
study, and continuing using contraception and refrain from fathering a child for
6 months following the study drug; a condom is required to be used also by
vasectomized men as well as during intercourse with a male partner in order to
prevent delivery of the study treatment via seminal fluid; female partner of
male study subject should use highly effective contraception during dosing of
any study agent and for 16 weeks after final dose of study therapy
- Note: hormonal contraception methods (eg, oral, injected, implanted) are not
allowed
- Note: woman are considered post-menopausal and not child bearing potential if
they have had 12 months of natural (spontaneous) amenorrhea with an appropriate
clinical profile (eg, age appropriate, history of vasomotor symptoms) or six
months of spontaneous amenorrhea with serum FSH levels > 40 mIU/mL and estradiol
< 20 pg/mL or have had surgical bilateral oophorectomy (with or without
hysterectomy) at least six weeks ago; in the case of oophorectomy alone, only
when the reproductive status of the woman has been confirmed by follow up
hormone level assessment is she considered not of child bearing potential
- Known diagnosis of human immunodeficiency virus (HIV) infection, hepatitis B or
hepatitis C
- History of another malignancy within 3 years, except cured basal cell carcinoma of
the skin or excised carcinoma in situ of the cervix
- Patient is unable or unwilling to abide by the study protocol or cooperate fully with
the investigator
Ages Eligible for Study
18 Years - N/A
Genders Eligible for Study
Both
Now accepting new patients
Contact Information
Primary Contact:
Anne Lynn Chang
650-721-7151
Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Erismodegib and Buparlisib in Treating Patients With Advanced or Metastatic Basal Cell Carcinoma
This pilot trial studies how well erismodegib and buparlisib work in treating patients withbasal cell carcinoma that has spread to other places in the body. Erismodegib and buparlisibmay stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Stanford is currently accepting patients for this trial. For more information, please contact Anne Lynn Chang at 650-721-7151 .
Lead Sponsor:
Stanford University
Collaborator: National Cancer Institute (NCI)
Stanford Investigator(s):
Intervention(s):
- Drug: buparlisib
- Drug: erismodegib
- Other: laboratory biomarker analysis
- Other: questionnaire administration
Phase:
N/A
Eligibility
Inclusion Criteria:
- Able to understand and sign informed consent
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Patients with metastatic BCC, histologic confirmation of distant BCC metastasis
- Patients with metastatic disease, target lesion must be measurable using computed
tomography (CT) or magnetic resonance imaging (MRI)
- Patients with locally advanced BCC are required to have disease that is considered
inoperable due to significant functional compromise or to have a medical
contraindication to surgery
- Patients with nevoid BCC syndrome (Gorlin syndrome) may enroll in this study but must
meet the criteria for locally advanced or metastatic disease listed above
- COHORT 2 ONLY: A Smoothened inhibitor must have been previously administered as
monotherapy
- Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
- Platelets >= 80 x10^9/L
- Hemoglobin (Hb) > 9 g/dL or values >= lower limit of normal (LLN) for site-specific
lab
- Total calcium (corrected for serum albumin) within normal limits (biphosphonate use
for malignant hypercalcemia control is not allowed)
- Magnesium >= the lower limit of normal
- Potassium within normal limits for the institution
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within normal
range (or =< 3.0 x upper limit of normal [ULN] if liver metastases are present)
- Serum bilirubin within normal range (or =< 1.5 x ULN if liver metastases are present;
or total bilirubin =< 3.0 x ULN with direct bilirubin within normal range in patients
with well-documented Gilbert Syndrome)
- Serum creatinine =< 1.5 x ULN or 24-hour clearance >= 50 mL/min
- Serum amylase =< ULN
- Serum lipase =< ULN
- Fasting plasma glucose =< 120 mg/dL (6.7 mmol/L)
- Negative serum pregnancy test within 72 hours before starting study treatment in
women with childbearing potential
- International normalized ratio (INR) =< 2
Exclusion Criteria:
- Patients who have received prior treatment with a P13K inhibitor
- Patients with a known hypersensitivity to buparlisib or to its excipients
- Patients with untreated brain metastases are excluded; however, patients with
metastatic central nervous system (CNS) tumors may participate in this trial, if the
patient is > 4 weeks from therapy completion (including radiation and/or surgery), is
clinically stable at the time of study entry and is not receiving corticosteroid
therapy
- Patients with acute or chronic liver, renal disease or pancreatitis
- Patients with baseline creatinine kinase (CK) > ULN
- Patients with the following mood disorders as judged by the Investigator or a
psychiatrist, or as a result of patient's mood assessment questionnaire:
- Medically documented history of or active major depressive episode, bipolar
disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of
suicidal attempt or ideation, or homicidal ideation (immediate risk of doing
harm to others)
- >= Common Terminology Criteria for Adverse Events (CTCAE) grade 3 anxiety
- Meets the cut-off score of >= 12 in the Patient Health Questionnaire (PHQ)-9 or
a cut-off of >= 15 in the Generalized Anxiety Disorder 7-item (GAD-7) mood
scale, respectively, or selects a positive response of "1, 2, or 3" to question
number 9 regarding potential for suicidal thoughts in the PHQ-9 (independent of
the total score of the PHQ-9)
- Patients with diarrhea >= CTCAE grade 2
- Patient has active cardiac disease including any of the following:
- Left ventricular ejection fraction (LVEF) < 50% as determined by multiple gated
acquisition (MUGA) scan or echocardiogram (ECHO)
- QTc > 450 msec on screening electrocardiogram (ECG) (using the QTcF formula)
- Angina pectoris that requires the use of anti-anginal medication
- Ventricular arrhythmias except for benign premature ventricular contractions
- Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled
with medication
- Conduction abnormality requiring a pacemaker
- Valvular disease with document compromise in cardiac function
- Symptomatic pericarditis
- Patient has a history of cardiac dysfunction including any of the following:
- Myocardial infraction within the last 6 months, documented by persistent
elevated cardiac enzymes or persistent regional wall abnormalities on assessment
of LVEF function
- History of documented congestive heart failure (New York Heart Association
functional classification III-IV)
- Documented cardiomyopathy
- Patient has poorly controlled diabetes mellitus (defined as hemoglobin A1C [HgA1c] >
ULN), steroid-induced diabetes mellitus or insulin dependent diabetes mellitus
- Other concurrent severe and/or uncontrolled concomitant medical conditions (eg,
active or uncontrolled infection) that could cause unacceptable safety risks or
compromise compliance with the protocol
- Significant symptomatic deterioration of lung function; if clinically indicated,
pulmonary function tests including measures of predicted lung volumes, diffusing
capacity of the lung for carbon monoxide (DLco), oxygen (O2) saturation at rest on
room air should be considered to exclude pneumonitis or pulmonary infiltrates
- Impairment of gastrointestinal (GI) function or GI disease that may significantly
alter the absorption of buparlisib (eg, ulcerative diseases, uncontrolled nausea,
vomiting, diarrhea, malabsorption syndrome, or small bowel resection); patients with
unresolved diarrhea will be excluded as previously indicated
- Patients who have been treated with any hematopoietic colony-stimulating growth
factors (eg, granulocyte-colony stimulating factor [G-CSF], granulocyte-macrophage
colony-stimulating factor [GM-CSF]) =< 2 weeks prior to starting study drug;
erythropoietin or darbepoetin therapy, if initiated at least 2 weeks prior to
enrollment, may be continued
- Patients who are currently receiving treatment with medication with a known risk to
prolong the QT interval or inducing Torsades de Pointes and the treatment cannot
either be discontinued or switched to a different medication prior to starting study
drug
- Patients receiving chronic treatment with steroids or another immunosuppressive agent
- Note: topical applications (eg, rash), inhaled sprays (eg, obstructive airways
diseases), eye drops or local injections (eg, intr-articular) are allowed;
patients with previously treated brain metastases, who are on stable low dose
corticosteriods treatment (eg, dexamethasone 2 mg/day, prednisolone 10 mg/day)
for at least 14 days before start of study treatment are eligible
- Patients who have taken herbal medications and certain fruits within 7 days prior to
starting study drug; herbal medications include, but are not limited to St. John's
Wort, Kava, ephedra (ma huang), dehydroepiandrosterone (DHEA), gingko biloba,
yohimbe, saw palmetto, and ginseng; fruits include the cytochrome P450, family 3,
subfamily A (CYP3A) inhibitors Seville oranges, grapefruit, pummelos, or exotic
citrus fruits
- Patients who are currently treated with drugs known to be moderate and strong
inhibitors or inducers of isoenzyme CYP3A, and the treatment cannot be discontinued
or switched to a different medication prior to starting study drug; please note that
co-treatment with weak inhibitors of CYP3A is allowed
- Patients who have received chemotherapy or targeted anticancer therapy =< 4 weeks (6
weeks for nitrosourea, antibodies or mitomycin-C) prior to starting study drug must
recover to a grade 1 before starting the trial
- Patients who have received any continuous or intermittent small molecule therapeutics
(excluding monoclonal antibodies) =< 5 effective half lives prior to starting study
drug or who have not recovered from side effects of such therapy
- Use of statin drugs or other medications known to associate with rhabdomyolysis;
these drugs must be discontinued at enrollment
- Patients who have received wide field radiotherapy =< 4 weeks or limited field
radiation for palliation =< 2 weeks prior to starting study drug or who have not
recovered from side effects of such therapy
- Patients who have undergone major surgery =< 2 weeks prior to starting study drug or
who have not recovered from side effects of such therapy
- Patients who are currently taking therapeutic doses of warfarin sodium or any other
coumadin-derivative anticoagulant; low molecular weight heparin is allowed
- Women who are pregnant or breast feeding or adults of reproductive potential not
employing an effective method of birth control; double barrier contraceptives must be
used through the trial by both sexes; oral, implantable, or injectable contraceptives
may be affected by cytochrome P450 interactions, and are therefore not considered
effective for this study; women of child-bearing potential, defined as sexually
mature women who have not undergone a hysterectomy or who have not been naturally
postmenopausal for at least 12 consecutive months (ie, who has had menses any time in
the preceding 12 consecutive months), must have a negative serum pregnancy test =< 72
hours prior to initiating treatment
- Women are considered post-menopausal and not of child bearing potential if they
have had 12 months of natural (spontaneous) amenorrhea with an appropriate
clinical profile (eg, age appropriate, history of vasomotor symptoms) or six
months of spontaneous amenorrhea with serum follicle stimulating hormone (FSH)
levels > 40 mIU/mL (for US only: and estradiol < 20 pg/mL) or have had surgical
bilateral oophorectomy (with or without hysterectomy) at least six weeks ago; in
the case of oophorectomy alone, only when the reproductive status of the woman
has been confirmed by follow up hormone level assessment is she considered not
of child bearing potential
- Women of child-bearing potential, defined as all women physiologically capable
of becoming pregnant, must use highly effective contraception during the study
and through 20 months after the final dose of study treatment; for males with
partners with childbearing potential, highly effective contraception is required
for 6 months; the highly effective contraception is defined as either:
- True abstinence: when this is in line with the preferred and usual
lifestyle of the subject; periodic abstinence (eg, calendar, ovulation,
symptothermal, post-ovulation methods) and withdrawal are not acceptable
methods of contraception
- Sterilization: have had surgical bilateral oophorectomy (with or without
hysterectomy) or tubal ligation at least six weeks ago; in case of
oophorectomy alone, only when the reproductive status of the woman has been
confirmed by follow up hormone level assessment
- Male partner sterilization (with the appropriate post-vasectomy
documentation of the absence of sperm in the ejaculate); for female
subjects on the study, the vasectomized male partner should be the sole
partner for that patient
- Use of a combination of any two of the following (a+b):
- a. Placement of an intrauterine device (IUD) or intrauterine system
(IUS)
- b. Barrier methods of contraception: condom or occlusive cap
(diaphragm or cervical/vault caps) with spermicidal
foam/gel/film/cream/vaginal suppository
- Oral contraception, injected or implanted hormonal methods are not allowed
- Fertile males, must use highly effective (double barrier) methods of
contraception (eg, spermicidal gel plus condom) for the entire duration of the
study, and continuing using contraception and refrain from fathering a child for
6 months following the study drug; a condom is required to be used also by
vasectomized men as well as during intercourse with a male partner in order to
prevent delivery of the study treatment via seminal fluid; female partner of
male study subject should use highly effective contraception during dosing of
any study agent and for 16 weeks after final dose of study therapy
- Note: hormonal contraception methods (eg, oral, injected, implanted) are not
allowed
- Note: woman are considered post-menopausal and not child bearing potential if
they have had 12 months of natural (spontaneous) amenorrhea with an appropriate
clinical profile (eg, age appropriate, history of vasomotor symptoms) or six
months of spontaneous amenorrhea with serum FSH levels > 40 mIU/mL and estradiol
< 20 pg/mL or have had surgical bilateral oophorectomy (with or without
hysterectomy) at least six weeks ago; in the case of oophorectomy alone, only
when the reproductive status of the woman has been confirmed by follow up
hormone level assessment is she considered not of child bearing potential
- Known diagnosis of human immunodeficiency virus (HIV) infection, hepatitis B or
hepatitis C
- History of another malignancy within 3 years, except cured basal cell carcinoma of
the skin or excised carcinoma in situ of the cervix
- Patient is unable or unwilling to abide by the study protocol or cooperate fully with
the investigator
Ages Eligible for Study
18 Years - N/A
Genders Eligible for Study
Both
Now accepting new patients
Contact Information
Primary Contact:
Anne Lynn Chang
650-721-7151
Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Erismodegib and Buparlisib in Treating Patients With Advanced or Metastatic Basal Cell Carcinoma
This pilot trial studies how well erismodegib and buparlisib work in treating patients withbasal cell carcinoma that has spread to other places in the body. Erismodegib and buparlisibmay stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Stanford is currently accepting patients for this trial. For more information, please contact Anne Lynn Chang at 650-721-7151 .
Lead Sponsor:
Stanford University
Collaborator: National Cancer Institute (NCI)
Stanford Investigator(s):
Intervention(s):
- Drug: buparlisib
- Drug: erismodegib
- Other: laboratory biomarker analysis
- Other: questionnaire administration
Phase:
N/A
Eligibility
Inclusion Criteria:
- Able to understand and sign informed consent
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Patients with metastatic BCC, histologic confirmation of distant BCC metastasis
- Patients with metastatic disease, target lesion must be measurable using computed
tomography (CT) or magnetic resonance imaging (MRI)
- Patients with locally advanced BCC are required to have disease that is considered
inoperable due to significant functional compromise or to have a medical
contraindication to surgery
- Patients with nevoid BCC syndrome (Gorlin syndrome) may enroll in this study but must
meet the criteria for locally advanced or metastatic disease listed above
- COHORT 2 ONLY: A Smoothened inhibitor must have been previously administered as
monotherapy
- Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
- Platelets >= 80 x10^9/L
- Hemoglobin (Hb) > 9 g/dL or values >= lower limit of normal (LLN) for site-specific
lab
- Total calcium (corrected for serum albumin) within normal limits (biphosphonate use
for malignant hypercalcemia control is not allowed)
- Magnesium >= the lower limit of normal
- Potassium within normal limits for the institution
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within normal
range (or =< 3.0 x upper limit of normal [ULN] if liver metastases are present)
- Serum bilirubin within normal range (or =< 1.5 x ULN if liver metastases are present;
or total bilirubin =< 3.0 x ULN with direct bilirubin within normal range in patients
with well-documented Gilbert Syndrome)
- Serum creatinine =< 1.5 x ULN or 24-hour clearance >= 50 mL/min
- Serum amylase =< ULN
- Serum lipase =< ULN
- Fasting plasma glucose =< 120 mg/dL (6.7 mmol/L)
- Negative serum pregnancy test within 72 hours before starting study treatment in
women with childbearing potential
- International normalized ratio (INR) =< 2
Exclusion Criteria:
- Patients who have received prior treatment with a P13K inhibitor
- Patients with a known hypersensitivity to buparlisib or to its excipients
- Patients with untreated brain metastases are excluded; however, patients with
metastatic central nervous system (CNS) tumors may participate in this trial, if the
patient is > 4 weeks from therapy completion (including radiation and/or surgery), is
clinically stable at the time of study entry and is not receiving corticosteroid
therapy
- Patients with acute or chronic liver, renal disease or pancreatitis
- Patients with baseline creatinine kinase (CK) > ULN
- Patients with the following mood disorders as judged by the Investigator or a
psychiatrist, or as a result of patient's mood assessment questionnaire:
- Medically documented history of or active major depressive episode, bipolar
disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of
suicidal attempt or ideation, or homicidal ideation (immediate risk of doing
harm to others)
- >= Common Terminology Criteria for Adverse Events (CTCAE) grade 3 anxiety
- Meets the cut-off score of >= 12 in the Patient Health Questionnaire (PHQ)-9 or
a cut-off of >= 15 in the Generalized Anxiety Disorder 7-item (GAD-7) mood
scale, respectively, or selects a positive response of "1, 2, or 3" to question
number 9 regarding potential for suicidal thoughts in the PHQ-9 (independent of
the total score of the PHQ-9)
- Patients with diarrhea >= CTCAE grade 2
- Patient has active cardiac disease including any of the following:
- Left ventricular ejection fraction (LVEF) < 50% as determined by multiple gated
acquisition (MUGA) scan or echocardiogram (ECHO)
- QTc > 450 msec on screening electrocardiogram (ECG) (using the QTcF formula)
- Angina pectoris that requires the use of anti-anginal medication
- Ventricular arrhythmias except for benign premature ventricular contractions
- Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled
with medication
- Conduction abnormality requiring a pacemaker
- Valvular disease with document compromise in cardiac function
- Symptomatic pericarditis
- Patient has a history of cardiac dysfunction including any of the following:
- Myocardial infraction within the last 6 months, documented by persistent
elevated cardiac enzymes or persistent regional wall abnormalities on assessment
of LVEF function
- History of documented congestive heart failure (New York Heart Association
functional classification III-IV)
- Documented cardiomyopathy
- Patient has poorly controlled diabetes mellitus (defined as hemoglobin A1C [HgA1c] >
ULN), steroid-induced diabetes mellitus or insulin dependent diabetes mellitus
- Other concurrent severe and/or uncontrolled concomitant medical conditions (eg,
active or uncontrolled infection) that could cause unacceptable safety risks or
compromise compliance with the protocol
- Significant symptomatic deterioration of lung function; if clinically indicated,
pulmonary function tests including measures of predicted lung volumes, diffusing
capacity of the lung for carbon monoxide (DLco), oxygen (O2) saturation at rest on
room air should be considered to exclude pneumonitis or pulmonary infiltrates
- Impairment of gastrointestinal (GI) function or GI disease that may significantly
alter the absorption of buparlisib (eg, ulcerative diseases, uncontrolled nausea,
vomiting, diarrhea, malabsorption syndrome, or small bowel resection); patients with
unresolved diarrhea will be excluded as previously indicated
- Patients who have been treated with any hematopoietic colony-stimulating growth
factors (eg, granulocyte-colony stimulating factor [G-CSF], granulocyte-macrophage
colony-stimulating factor [GM-CSF]) =< 2 weeks prior to starting study drug;
erythropoietin or darbepoetin therapy, if initiated at least 2 weeks prior to
enrollment, may be continued
- Patients who are currently receiving treatment with medication with a known risk to
prolong the QT interval or inducing Torsades de Pointes and the treatment cannot
either be discontinued or switched to a different medication prior to starting study
drug
- Patients receiving chronic treatment with steroids or another immunosuppressive agent
- Note: topical applications (eg, rash), inhaled sprays (eg, obstructive airways
diseases), eye drops or local injections (eg, intr-articular) are allowed;
patients with previously treated brain metastases, who are on stable low dose
corticosteriods treatment (eg, dexamethasone 2 mg/day, prednisolone 10 mg/day)
for at least 14 days before start of study treatment are eligible
- Patients who have taken herbal medications and certain fruits within 7 days prior to
starting study drug; herbal medications include, but are not limited to St. John's
Wort, Kava, ephedra (ma huang), dehydroepiandrosterone (DHEA), gingko biloba,
yohimbe, saw palmetto, and ginseng; fruits include the cytochrome P450, family 3,
subfamily A (CYP3A) inhibitors Seville oranges, grapefruit, pummelos, or exotic
citrus fruits
- Patients who are currently treated with drugs known to be moderate and strong
inhibitors or inducers of isoenzyme CYP3A, and the treatment cannot be discontinued
or switched to a different medication prior to starting study drug; please note that
co-treatment with weak inhibitors of CYP3A is allowed
- Patients who have received chemotherapy or targeted anticancer therapy =< 4 weeks (6
weeks for nitrosourea, antibodies or mitomycin-C) prior to starting study drug must
recover to a grade 1 before starting the trial
- Patients who have received any continuous or intermittent small molecule therapeutics
(excluding monoclonal antibodies) =< 5 effective half lives prior to starting study
drug or who have not recovered from side effects of such therapy
- Use of statin drugs or other medications known to associate with rhabdomyolysis;
these drugs must be discontinued at enrollment
- Patients who have received wide field radiotherapy =< 4 weeks or limited field
radiation for palliation =< 2 weeks prior to starting study drug or who have not
recovered from side effects of such therapy
- Patients who have undergone major surgery =< 2 weeks prior to starting study drug or
who have not recovered from side effects of such therapy
- Patients who are currently taking therapeutic doses of warfarin sodium or any other
coumadin-derivative anticoagulant; low molecular weight heparin is allowed
- Women who are pregnant or breast feeding or adults of reproductive potential not
employing an effective method of birth control; double barrier contraceptives must be
used through the trial by both sexes; oral, implantable, or injectable contraceptives
may be affected by cytochrome P450 interactions, and are therefore not considered
effective for this study; women of child-bearing potential, defined as sexually
mature women who have not undergone a hysterectomy or who have not been naturally
postmenopausal for at least 12 consecutive months (ie, who has had menses any time in
the preceding 12 consecutive months), must have a negative serum pregnancy test =< 72
hours prior to initiating treatment
- Women are considered post-menopausal and not of child bearing potential if they
have had 12 months of natural (spontaneous) amenorrhea with an appropriate
clinical profile (eg, age appropriate, history of vasomotor symptoms) or six
months of spontaneous amenorrhea with serum follicle stimulating hormone (FSH)
levels > 40 mIU/mL (for US only: and estradiol < 20 pg/mL) or have had surgical
bilateral oophorectomy (with or without hysterectomy) at least six weeks ago; in
the case of oophorectomy alone, only when the reproductive status of the woman
has been confirmed by follow up hormone level assessment is she considered not
of child bearing potential
- Women of child-bearing potential, defined as all women physiologically capable
of becoming pregnant, must use highly effective contraception during the study
and through 20 months after the final dose of study treatment; for males with
partners with childbearing potential, highly effective contraception is required
for 6 months; the highly effective contraception is defined as either:
- True abstinence: when this is in line with the preferred and usual
lifestyle of the subject; periodic abstinence (eg, calendar, ovulation,
symptothermal, post-ovulation methods) and withdrawal are not acceptable
methods of contraception
- Sterilization: have had surgical bilateral oophorectomy (with or without
hysterectomy) or tubal ligation at least six weeks ago; in case of
oophorectomy alone, only when the reproductive status of the woman has been
confirmed by follow up hormone level assessment
- Male partner sterilization (with the appropriate post-vasectomy
documentation of the absence of sperm in the ejaculate); for female
subjects on the study, the vasectomized male partner should be the sole
partner for that patient
- Use of a combination of any two of the following (a+b):
- a. Placement of an intrauterine device (IUD) or intrauterine system
(IUS)
- b. Barrier methods of contraception: condom or occlusive cap
(diaphragm or cervical/vault caps) with spermicidal
foam/gel/film/cream/vaginal suppository
- Oral contraception, injected or implanted hormonal methods are not allowed
- Fertile males, must use highly effective (double barrier) methods of
contraception (eg, spermicidal gel plus condom) for the entire duration of the
study, and continuing using contraception and refrain from fathering a child for
6 months following the study drug; a condom is required to be used also by
vasectomized men as well as during intercourse with a male partner in order to
prevent delivery of the study treatment via seminal fluid; female partner of
male study subject should use highly effective contraception during dosing of
any study agent and for 16 weeks after final dose of study therapy
- Note: hormonal contraception methods (eg, oral, injected, implanted) are not
allowed
- Note: woman are considered post-menopausal and not child bearing potential if
they have had 12 months of natural (spontaneous) amenorrhea with an appropriate
clinical profile (eg, age appropriate, history of vasomotor symptoms) or six
months of spontaneous amenorrhea with serum FSH levels > 40 mIU/mL and estradiol
< 20 pg/mL or have had surgical bilateral oophorectomy (with or without
hysterectomy) at least six weeks ago; in the case of oophorectomy alone, only
when the reproductive status of the woman has been confirmed by follow up
hormone level assessment is she considered not of child bearing potential
- Known diagnosis of human immunodeficiency virus (HIV) infection, hepatitis B or
hepatitis C
- History of another malignancy within 3 years, except cured basal cell carcinoma of
the skin or excised carcinoma in situ of the cervix
- Patient is unable or unwilling to abide by the study protocol or cooperate fully with
the investigator
Ages Eligible for Study
18 Years - N/A
Genders Eligible for Study
Both
Now accepting new patients
Contact Information
Primary Contact:
Anne Lynn Chang
650-721-7151
Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Erismodegib and Buparlisib in Treating Patients With Advanced or Metastatic Basal Cell Carcinoma
This pilot trial studies how well erismodegib and buparlisib work in treating patients withbasal cell carcinoma that has spread to other places in the body. Erismodegib and buparlisibmay stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Stanford is currently accepting patients for this trial. For more information, please contact Anne Lynn Chang at 650-721-7151 .
Lead Sponsor:
Stanford University
Collaborator: National Cancer Institute (NCI)
Stanford Investigator(s):
Intervention(s):
- Drug: buparlisib
- Drug: erismodegib
- Other: laboratory biomarker analysis
- Other: questionnaire administration
Phase:
N/A
Eligibility
Inclusion Criteria:
- Able to understand and sign informed consent
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Patients with metastatic BCC, histologic confirmation of distant BCC metastasis
- Patients with metastatic disease, target lesion must be measurable using computed
tomography (CT) or magnetic resonance imaging (MRI)
- Patients with locally advanced BCC are required to have disease that is considered
inoperable due to significant functional compromise or to have a medical
contraindication to surgery
- Patients with nevoid BCC syndrome (Gorlin syndrome) may enroll in this study but must
meet the criteria for locally advanced or metastatic disease listed above
- COHORT 2 ONLY: A Smoothened inhibitor must have been previously administered as
monotherapy
- Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
- Platelets >= 80 x10^9/L
- Hemoglobin (Hb) > 9 g/dL or values >= lower limit of normal (LLN) for site-specific
lab
- Total calcium (corrected for serum albumin) within normal limits (biphosphonate use
for malignant hypercalcemia control is not allowed)
- Magnesium >= the lower limit of normal
- Potassium within normal limits for the institution
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within normal
range (or =< 3.0 x upper limit of normal [ULN] if liver metastases are present)
- Serum bilirubin within normal range (or =< 1.5 x ULN if liver metastases are present;
or total bilirubin =< 3.0 x ULN with direct bilirubin within normal range in patients
with well-documented Gilbert Syndrome)
- Serum creatinine =< 1.5 x ULN or 24-hour clearance >= 50 mL/min
- Serum amylase =< ULN
- Serum lipase =< ULN
- Fasting plasma glucose =< 120 mg/dL (6.7 mmol/L)
- Negative serum pregnancy test within 72 hours before starting study treatment in
women with childbearing potential
- International normalized ratio (INR) =< 2
Exclusion Criteria:
- Patients who have received prior treatment with a P13K inhibitor
- Patients with a known hypersensitivity to buparlisib or to its excipients
- Patients with untreated brain metastases are excluded; however, patients with
metastatic central nervous system (CNS) tumors may participate in this trial, if the
patient is > 4 weeks from therapy completion (including radiation and/or surgery), is
clinically stable at the time of study entry and is not receiving corticosteroid
therapy
- Patients with acute or chronic liver, renal disease or pancreatitis
- Patients with baseline creatinine kinase (CK) > ULN
- Patients with the following mood disorders as judged by the Investigator or a
psychiatrist, or as a result of patient's mood assessment questionnaire:
- Medically documented history of or active major depressive episode, bipolar
disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of
suicidal attempt or ideation, or homicidal ideation (immediate risk of doing
harm to others)
- >= Common Terminology Criteria for Adverse Events (CTCAE) grade 3 anxiety
- Meets the cut-off score of >= 12 in the Patient Health Questionnaire (PHQ)-9 or
a cut-off of >= 15 in the Generalized Anxiety Disorder 7-item (GAD-7) mood
scale, respectively, or selects a positive response of "1, 2, or 3" to question
number 9 regarding potential for suicidal thoughts in the PHQ-9 (independent of
the total score of the PHQ-9)
- Patients with diarrhea >= CTCAE grade 2
- Patient has active cardiac disease including any of the following:
- Left ventricular ejection fraction (LVEF) < 50% as determined by multiple gated
acquisition (MUGA) scan or echocardiogram (ECHO)
- QTc > 450 msec on screening electrocardiogram (ECG) (using the QTcF formula)
- Angina pectoris that requires the use of anti-anginal medication
- Ventricular arrhythmias except for benign premature ventricular contractions
- Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled
with medication
- Conduction abnormality requiring a pacemaker
- Valvular disease with document compromise in cardiac function
- Symptomatic pericarditis
- Patient has a history of cardiac dysfunction including any of the following:
- Myocardial infraction within the last 6 months, documented by persistent
elevated cardiac enzymes or persistent regional wall abnormalities on assessment
of LVEF function
- History of documented congestive heart failure (New York Heart Association
functional classification III-IV)
- Documented cardiomyopathy
- Patient has poorly controlled diabetes mellitus (defined as hemoglobin A1C [HgA1c] >
ULN), steroid-induced diabetes mellitus or insulin dependent diabetes mellitus
- Other concurrent severe and/or uncontrolled concomitant medical conditions (eg,
active or uncontrolled infection) that could cause unacceptable safety risks or
compromise compliance with the protocol
- Significant symptomatic deterioration of lung function; if clinically indicated,
pulmonary function tests including measures of predicted lung volumes, diffusing
capacity of the lung for carbon monoxide (DLco), oxygen (O2) saturation at rest on
room air should be considered to exclude pneumonitis or pulmonary infiltrates
- Impairment of gastrointestinal (GI) function or GI disease that may significantly
alter the absorption of buparlisib (eg, ulcerative diseases, uncontrolled nausea,
vomiting, diarrhea, malabsorption syndrome, or small bowel resection); patients with
unresolved diarrhea will be excluded as previously indicated
- Patients who have been treated with any hematopoietic colony-stimulating growth
factors (eg, granulocyte-colony stimulating factor [G-CSF], granulocyte-macrophage
colony-stimulating factor [GM-CSF]) =< 2 weeks prior to starting study drug;
erythropoietin or darbepoetin therapy, if initiated at least 2 weeks prior to
enrollment, may be continued
- Patients who are currently receiving treatment with medication with a known risk to
prolong the QT interval or inducing Torsades de Pointes and the treatment cannot
either be discontinued or switched to a different medication prior to starting study
drug
- Patients receiving chronic treatment with steroids or another immunosuppressive agent
- Note: topical applications (eg, rash), inhaled sprays (eg, obstructive airways
diseases), eye drops or local injections (eg, intr-articular) are allowed;
patients with previously treated brain metastases, who are on stable low dose
corticosteriods treatment (eg, dexamethasone 2 mg/day, prednisolone 10 mg/day)
for at least 14 days before start of study treatment are eligible
- Patients who have taken herbal medications and certain fruits within 7 days prior to
starting study drug; herbal medications include, but are not limited to St. John's
Wort, Kava, ephedra (ma huang), dehydroepiandrosterone (DHEA), gingko biloba,
yohimbe, saw palmetto, and ginseng; fruits include the cytochrome P450, family 3,
subfamily A (CYP3A) inhibitors Seville oranges, grapefruit, pummelos, or exotic
citrus fruits
- Patients who are currently treated with drugs known to be moderate and strong
inhibitors or inducers of isoenzyme CYP3A, and the treatment cannot be discontinued
or switched to a different medication prior to starting study drug; please note that
co-treatment with weak inhibitors of CYP3A is allowed
- Patients who have received chemotherapy or targeted anticancer therapy =< 4 weeks (6
weeks for nitrosourea, antibodies or mitomycin-C) prior to starting study drug must
recover to a grade 1 before starting the trial
- Patients who have received any continuous or intermittent small molecule therapeutics
(excluding monoclonal antibodies) =< 5 effective half lives prior to starting study
drug or who have not recovered from side effects of such therapy
- Use of statin drugs or other medications known to associate with rhabdomyolysis;
these drugs must be discontinued at enrollment
- Patients who have received wide field radiotherapy =< 4 weeks or limited field
radiation for palliation =< 2 weeks prior to starting study drug or who have not
recovered from side effects of such therapy
- Patients who have undergone major surgery =< 2 weeks prior to starting study drug or
who have not recovered from side effects of such therapy
- Patients who are currently taking therapeutic doses of warfarin sodium or any other
coumadin-derivative anticoagulant; low molecular weight heparin is allowed
- Women who are pregnant or breast feeding or adults of reproductive potential not
employing an effective method of birth control; double barrier contraceptives must be
used through the trial by both sexes; oral, implantable, or injectable contraceptives
may be affected by cytochrome P450 interactions, and are therefore not considered
effective for this study; women of child-bearing potential, defined as sexually
mature women who have not undergone a hysterectomy or who have not been naturally
postmenopausal for at least 12 consecutive months (ie, who has had menses any time in
the preceding 12 consecutive months), must have a negative serum pregnancy test =< 72
hours prior to initiating treatment
- Women are considered post-menopausal and not of child bearing potential if they
have had 12 months of natural (spontaneous) amenorrhea with an appropriate
clinical profile (eg, age appropriate, history of vasomotor symptoms) or six
months of spontaneous amenorrhea with serum follicle stimulating hormone (FSH)
levels > 40 mIU/mL (for US only: and estradiol < 20 pg/mL) or have had surgical
bilateral oophorectomy (with or without hysterectomy) at least six weeks ago; in
the case of oophorectomy alone, only when the reproductive status of the woman
has been confirmed by follow up hormone level assessment is she considered not
of child bearing potential
- Women of child-bearing potential, defined as all women physiologically capable
of becoming pregnant, must use highly effective contraception during the study
and through 20 months after the final dose of study treatment; for males with
partners with childbearing potential, highly effective contraception is required
for 6 months; the highly effective contraception is defined as either:
- True abstinence: when this is in line with the preferred and usual
lifestyle of the subject; periodic abstinence (eg, calendar, ovulation,
symptothermal, post-ovulation methods) and withdrawal are not acceptable
methods of contraception
- Sterilization: have had surgical bilateral oophorectomy (with or without
hysterectomy) or tubal ligation at least six weeks ago; in case of
oophorectomy alone, only when the reproductive status of the woman has been
confirmed by follow up hormone level assessment
- Male partner sterilization (with the appropriate post-vasectomy
documentation of the absence of sperm in the ejaculate); for female
subjects on the study, the vasectomized male partner should be the sole
partner for that patient
- Use of a combination of any two of the following (a+b):
- a. Placement of an intrauterine device (IUD) or intrauterine system
(IUS)
- b. Barrier methods of contraception: condom or occlusive cap
(diaphragm or cervical/vault caps) with spermicidal
foam/gel/film/cream/vaginal suppository
- Oral contraception, injected or implanted hormonal methods are not allowed
- Fertile males, must use highly effective (double barrier) methods of
contraception (eg, spermicidal gel plus condom) for the entire duration of the
study, and continuing using contraception and refrain from fathering a child for
6 months following the study drug; a condom is required to be used also by
vasectomized men as well as during intercourse with a male partner in order to
prevent delivery of the study treatment via seminal fluid; female partner of
male study subject should use highly effective contraception during dosing of
any study agent and for 16 weeks after final dose of study therapy
- Note: hormonal contraception methods (eg, oral, injected, implanted) are not
allowed
- Note: woman are considered post-menopausal and not child bearing potential if
they have had 12 months of natural (spontaneous) amenorrhea with an appropriate
clinical profile (eg, age appropriate, history of vasomotor symptoms) or six
months of spontaneous amenorrhea with serum FSH levels > 40 mIU/mL and estradiol
< 20 pg/mL or have had surgical bilateral oophorectomy (with or without
hysterectomy) at least six weeks ago; in the case of oophorectomy alone, only
when the reproductive status of the woman has been confirmed by follow up
hormone level assessment is she considered not of child bearing potential
- Known diagnosis of human immunodeficiency virus (HIV) infection, hepatitis B or
hepatitis C
- History of another malignancy within 3 years, except cured basal cell carcinoma of
the skin or excised carcinoma in situ of the cervix
- Patient is unable or unwilling to abide by the study protocol or cooperate fully with
the investigator
Ages Eligible for Study
18 Years - N/A
Genders Eligible for Study
Both
Now accepting new patients
Contact Information
Primary Contact:
Anne Lynn Chang
650-721-7151
Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Erismodegib and Buparlisib in Treating Patients With Advanced or Metastatic Basal Cell Carcinoma
This pilot trial studies how well erismodegib and buparlisib work in treating patients withbasal cell carcinoma that has spread to other places in the body. Erismodegib and buparlisibmay stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Stanford is currently accepting patients for this trial. For more information, please contact Anne Lynn Chang at 650-721-7151 .
Lead Sponsor:
Stanford University
Collaborator: National Cancer Institute (NCI)
Stanford Investigator(s):
Intervention(s):
- Drug: buparlisib
- Drug: erismodegib
- Other: laboratory biomarker analysis
- Other: questionnaire administration
Phase:
N/A
Eligibility
Inclusion Criteria:
- Able to understand and sign informed consent
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Patients with metastatic BCC, histologic confirmation of distant BCC metastasis
- Patients with metastatic disease, target lesion must be measurable using computed
tomography (CT) or magnetic resonance imaging (MRI)
- Patients with locally advanced BCC are required to have disease that is considered
inoperable due to significant functional compromise or to have a medical
contraindication to surgery
- Patients with nevoid BCC syndrome (Gorlin syndrome) may enroll in this study but must
meet the criteria for locally advanced or metastatic disease listed above
- COHORT 2 ONLY: A Smoothened inhibitor must have been previously administered as
monotherapy
- Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
- Platelets >= 80 x10^9/L
- Hemoglobin (Hb) > 9 g/dL or values >= lower limit of normal (LLN) for site-specific
lab
- Total calcium (corrected for serum albumin) within normal limits (biphosphonate use
for malignant hypercalcemia control is not allowed)
- Magnesium >= the lower limit of normal
- Potassium within normal limits for the institution
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within normal
range (or =< 3.0 x upper limit of normal [ULN] if liver metastases are present)
- Serum bilirubin within normal range (or =< 1.5 x ULN if liver metastases are present;
or total bilirubin =< 3.0 x ULN with direct bilirubin within normal range in patients
with well-documented Gilbert Syndrome)
- Serum creatinine =< 1.5 x ULN or 24-hour clearance >= 50 mL/min
- Serum amylase =< ULN
- Serum lipase =< ULN
- Fasting plasma glucose =< 120 mg/dL (6.7 mmol/L)
- Negative serum pregnancy test within 72 hours before starting study treatment in
women with childbearing potential
- International normalized ratio (INR) =< 2
Exclusion Criteria:
- Patients who have received prior treatment with a P13K inhibitor
- Patients with a known hypersensitivity to buparlisib or to its excipients
- Patients with untreated brain metastases are excluded; however, patients with
metastatic central nervous system (CNS) tumors may participate in this trial, if the
patient is > 4 weeks from therapy completion (including radiation and/or surgery), is
clinically stable at the time of study entry and is not receiving corticosteroid
therapy
- Patients with acute or chronic liver, renal disease or pancreatitis
- Patients with baseline creatinine kinase (CK) > ULN
- Patients with the following mood disorders as judged by the Investigator or a
psychiatrist, or as a result of patient's mood assessment questionnaire:
- Medically documented history of or active major depressive episode, bipolar
disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of
suicidal attempt or ideation, or homicidal ideation (immediate risk of doing
harm to others)
- >= Common Terminology Criteria for Adverse Events (CTCAE) grade 3 anxiety
- Meets the cut-off score of >= 12 in the Patient Health Questionnaire (PHQ)-9 or
a cut-off of >= 15 in the Generalized Anxiety Disorder 7-item (GAD-7) mood
scale, respectively, or selects a positive response of "1, 2, or 3" to question
number 9 regarding potential for suicidal thoughts in the PHQ-9 (independent of
the total score of the PHQ-9)
- Patients with diarrhea >= CTCAE grade 2
- Patient has active cardiac disease including any of the following:
- Left ventricular ejection fraction (LVEF) < 50% as determined by multiple gated
acquisition (MUGA) scan or echocardiogram (ECHO)
- QTc > 450 msec on screening electrocardiogram (ECG) (using the QTcF formula)
- Angina pectoris that requires the use of anti-anginal medication
- Ventricular arrhythmias except for benign premature ventricular contractions
- Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled
with medication
- Conduction abnormality requiring a pacemaker
- Valvular disease with document compromise in cardiac function
- Symptomatic pericarditis
- Patient has a history of cardiac dysfunction including any of the following:
- Myocardial infraction within the last 6 months, documented by persistent
elevated cardiac enzymes or persistent regional wall abnormalities on assessment
of LVEF function
- History of documented congestive heart failure (New York Heart Association
functional classification III-IV)
- Documented cardiomyopathy
- Patient has poorly controlled diabetes mellitus (defined as hemoglobin A1C [HgA1c] >
ULN), steroid-induced diabetes mellitus or insulin dependent diabetes mellitus
- Other concurrent severe and/or uncontrolled concomitant medical conditions (eg,
active or uncontrolled infection) that could cause unacceptable safety risks or
compromise compliance with the protocol
- Significant symptomatic deterioration of lung function; if clinically indicated,
pulmonary function tests including measures of predicted lung volumes, diffusing
capacity of the lung for carbon monoxide (DLco), oxygen (O2) saturation at rest on
room air should be considered to exclude pneumonitis or pulmonary infiltrates
- Impairment of gastrointestinal (GI) function or GI disease that may significantly
alter the absorption of buparlisib (eg, ulcerative diseases, uncontrolled nausea,
vomiting, diarrhea, malabsorption syndrome, or small bowel resection); patients with
unresolved diarrhea will be excluded as previously indicated
- Patients who have been treated with any hematopoietic colony-stimulating growth
factors (eg, granulocyte-colony stimulating factor [G-CSF], granulocyte-macrophage
colony-stimulating factor [GM-CSF]) =< 2 weeks prior to starting study drug;
erythropoietin or darbepoetin therapy, if initiated at least 2 weeks prior to
enrollment, may be continued
- Patients who are currently receiving treatment with medication with a known risk to
prolong the QT interval or inducing Torsades de Pointes and the treatment cannot
either be discontinued or switched to a different medication prior to starting study
drug
- Patients receiving chronic treatment with steroids or another immunosuppressive agent
- Note: topical applications (eg, rash), inhaled sprays (eg, obstructive airways
diseases), eye drops or local injections (eg, intr-articular) are allowed;
patients with previously treated brain metastases, who are on stable low dose
corticosteriods treatment (eg, dexamethasone 2 mg/day, prednisolone 10 mg/day)
for at least 14 days before start of study treatment are eligible
- Patients who have taken herbal medications and certain fruits within 7 days prior to
starting study drug; herbal medications include, but are not limited to St. John's
Wort, Kava, ephedra (ma huang), dehydroepiandrosterone (DHEA), gingko biloba,
yohimbe, saw palmetto, and ginseng; fruits include the cytochrome P450, family 3,
subfamily A (CYP3A) inhibitors Seville oranges, grapefruit, pummelos, or exotic
citrus fruits
- Patients who are currently treated with drugs known to be moderate and strong
inhibitors or inducers of isoenzyme CYP3A, and the treatment cannot be discontinued
or switched to a different medication prior to starting study drug; please note that
co-treatment with weak inhibitors of CYP3A is allowed
- Patients who have received chemotherapy or targeted anticancer therapy =< 4 weeks (6
weeks for nitrosourea, antibodies or mitomycin-C) prior to starting study drug must
recover to a grade 1 before starting the trial
- Patients who have received any continuous or intermittent small molecule therapeutics
(excluding monoclonal antibodies) =< 5 effective half lives prior to starting study
drug or who have not recovered from side effects of such therapy
- Use of statin drugs or other medications known to associate with rhabdomyolysis;
these drugs must be discontinued at enrollment
- Patients who have received wide field radiotherapy =< 4 weeks or limited field
radiation for palliation =< 2 weeks prior to starting study drug or who have not
recovered from side effects of such therapy
- Patients who have undergone major surgery =< 2 weeks prior to starting study drug or
who have not recovered from side effects of such therapy
- Patients who are currently taking therapeutic doses of warfarin sodium or any other
coumadin-derivative anticoagulant; low molecular weight heparin is allowed
- Women who are pregnant or breast feeding or adults of reproductive potential not
employing an effective method of birth control; double barrier contraceptives must be
used through the trial by both sexes; oral, implantable, or injectable contraceptives
may be affected by cytochrome P450 interactions, and are therefore not considered
effective for this study; women of child-bearing potential, defined as sexually
mature women who have not undergone a hysterectomy or who have not been naturally
postmenopausal for at least 12 consecutive months (ie, who has had menses any time in
the preceding 12 consecutive months), must have a negative serum pregnancy test =< 72
hours prior to initiating treatment
- Women are considered post-menopausal and not of child bearing potential if they
have had 12 months of natural (spontaneous) amenorrhea with an appropriate
clinical profile (eg, age appropriate, history of vasomotor symptoms) or six
months of spontaneous amenorrhea with serum follicle stimulating hormone (FSH)
levels > 40 mIU/mL (for US only: and estradiol < 20 pg/mL) or have had surgical
bilateral oophorectomy (with or without hysterectomy) at least six weeks ago; in
the case of oophorectomy alone, only when the reproductive status of the woman
has been confirmed by follow up hormone level assessment is she considered not
of child bearing potential
- Women of child-bearing potential, defined as all women physiologically capable
of becoming pregnant, must use highly effective contraception during the study
and through 20 months after the final dose of study treatment; for males with
partners with childbearing potential, highly effective contraception is required
for 6 months; the highly effective contraception is defined as either:
- True abstinence: when this is in line with the preferred and usual
lifestyle of the subject; periodic abstinence (eg, calendar, ovulation,
symptothermal, post-ovulation methods) and withdrawal are not acceptable
methods of contraception
- Sterilization: have had surgical bilateral oophorectomy (with or without
hysterectomy) or tubal ligation at least six weeks ago; in case of
oophorectomy alone, only when the reproductive status of the woman has been
confirmed by follow up hormone level assessment
- Male partner sterilization (with the appropriate post-vasectomy
documentation of the absence of sperm in the ejaculate); for female
subjects on the study, the vasectomized male partner should be the sole
partner for that patient
- Use of a combination of any two of the following (a+b):
- a. Placement of an intrauterine device (IUD) or intrauterine system
(IUS)
- b. Barrier methods of contraception: condom or occlusive cap
(diaphragm or cervical/vault caps) with spermicidal
foam/gel/film/cream/vaginal suppository
- Oral contraception, injected or implanted hormonal methods are not allowed
- Fertile males, must use highly effective (double barrier) methods of
contraception (eg, spermicidal gel plus condom) for the entire duration of the
study, and continuing using contraception and refrain from fathering a child for
6 months following the study drug; a condom is required to be used also by
vasectomized men as well as during intercourse with a male partner in order to
prevent delivery of the study treatment via seminal fluid; female partner of
male study subject should use highly effective contraception during dosing of
any study agent and for 16 weeks after final dose of study therapy
- Note: hormonal contraception methods (eg, oral, injected, implanted) are not
allowed
- Note: woman are considered post-menopausal and not child bearing potential if
they have had 12 months of natural (spontaneous) amenorrhea with an appropriate
clinical profile (eg, age appropriate, history of vasomotor symptoms) or six
months of spontaneous amenorrhea with serum FSH levels > 40 mIU/mL and estradiol
< 20 pg/mL or have had surgical bilateral oophorectomy (with or without
hysterectomy) at least six weeks ago; in the case of oophorectomy alone, only
when the reproductive status of the woman has been confirmed by follow up
hormone level assessment is she considered not of child bearing potential
- Known diagnosis of human immunodeficiency virus (HIV) infection, hepatitis B or
hepatitis C
- History of another malignancy within 3 years, except cured basal cell carcinoma of
the skin or excised carcinoma in situ of the cervix
- Patient is unable or unwilling to abide by the study protocol or cooperate fully with
the investigator
Ages Eligible for Study
18 Years - N/A
Genders Eligible for Study
Both
Now accepting new patients
Contact Information
Primary Contact:
Anne Lynn Chang
650-721-7151
Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Erismodegib and Buparlisib in Treating Patients With Advanced or Metastatic Basal Cell Carcinoma
This pilot trial studies how well erismodegib and buparlisib work in treating patients withbasal cell carcinoma that has spread to other places in the body. Erismodegib and buparlisibmay stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Stanford is currently accepting patients for this trial. For more information, please contact Anne Lynn Chang at 650-721-7151 .
Lead Sponsor:
Stanford University
Collaborator: National Cancer Institute (NCI)
Stanford Investigator(s):
Intervention(s):
- Drug: buparlisib
- Drug: erismodegib
- Other: laboratory biomarker analysis
- Other: questionnaire administration
Phase:
N/A
Eligibility
Inclusion Criteria:
- Able to understand and sign informed consent
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Patients with metastatic BCC, histologic confirmation of distant BCC metastasis
- Patients with metastatic disease, target lesion must be measurable using computed
tomography (CT) or magnetic resonance imaging (MRI)
- Patients with locally advanced BCC are required to have disease that is considered
inoperable due to significant functional compromise or to have a medical
contraindication to surgery
- Patients with nevoid BCC syndrome (Gorlin syndrome) may enroll in this study but must
meet the criteria for locally advanced or metastatic disease listed above
- COHORT 2 ONLY: A Smoothened inhibitor must have been previously administered as
monotherapy
- Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
- Platelets >= 80 x10^9/L
- Hemoglobin (Hb) > 9 g/dL or values >= lower limit of normal (LLN) for site-specific
lab
- Total calcium (corrected for serum albumin) within normal limits (biphosphonate use
for malignant hypercalcemia control is not allowed)
- Magnesium >= the lower limit of normal
- Potassium within normal limits for the institution
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within normal
range (or =< 3.0 x upper limit of normal [ULN] if liver metastases are present)
- Serum bilirubin within normal range (or =< 1.5 x ULN if liver metastases are present;
or total bilirubin =< 3.0 x ULN with direct bilirubin within normal range in patients
with well-documented Gilbert Syndrome)
- Serum creatinine =< 1.5 x ULN or 24-hour clearance >= 50 mL/min
- Serum amylase =< ULN
- Serum lipase =< ULN
- Fasting plasma glucose =< 120 mg/dL (6.7 mmol/L)
- Negative serum pregnancy test within 72 hours before starting study treatment in
women with childbearing potential
- International normalized ratio (INR) =< 2
Exclusion Criteria:
- Patients who have received prior treatment with a P13K inhibitor
- Patients with a known hypersensitivity to buparlisib or to its excipients
- Patients with untreated brain metastases are excluded; however, patients with
metastatic central nervous system (CNS) tumors may participate in this trial, if the
patient is > 4 weeks from therapy completion (including radiation and/or surgery), is
clinically stable at the time of study entry and is not receiving corticosteroid
therapy
- Patients with acute or chronic liver, renal disease or pancreatitis
- Patients with baseline creatinine kinase (CK) > ULN
- Patients with the following mood disorders as judged by the Investigator or a
psychiatrist, or as a result of patient's mood assessment questionnaire:
- Medically documented history of or active major depressive episode, bipolar
disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of
suicidal attempt or ideation, or homicidal ideation (immediate risk of doing
harm to others)
- >= Common Terminology Criteria for Adverse Events (CTCAE) grade 3 anxiety
- Meets the cut-off score of >= 12 in the Patient Health Questionnaire (PHQ)-9 or
a cut-off of >= 15 in the Generalized Anxiety Disorder 7-item (GAD-7) mood
scale, respectively, or selects a positive response of "1, 2, or 3" to question
number 9 regarding potential for suicidal thoughts in the PHQ-9 (independent of
the total score of the PHQ-9)
- Patients with diarrhea >= CTCAE grade 2
- Patient has active cardiac disease including any of the following:
- Left ventricular ejection fraction (LVEF) < 50% as determined by multiple gated
acquisition (MUGA) scan or echocardiogram (ECHO)
- QTc > 450 msec on screening electrocardiogram (ECG) (using the QTcF formula)
- Angina pectoris that requires the use of anti-anginal medication
- Ventricular arrhythmias except for benign premature ventricular contractions
- Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled
with medication
- Conduction abnormality requiring a pacemaker
- Valvular disease with document compromise in cardiac function
- Symptomatic pericarditis
- Patient has a history of cardiac dysfunction including any of the following:
- Myocardial infraction within the last 6 months, documented by persistent
elevated cardiac enzymes or persistent regional wall abnormalities on assessment
of LVEF function
- History of documented congestive heart failure (New York Heart Association
functional classification III-IV)
- Documented cardiomyopathy
- Patient has poorly controlled diabetes mellitus (defined as hemoglobin A1C [HgA1c] >
ULN), steroid-induced diabetes mellitus or insulin dependent diabetes mellitus
- Other concurrent severe and/or uncontrolled concomitant medical conditions (eg,
active or uncontrolled infection) that could cause unacceptable safety risks or
compromise compliance with the protocol
- Significant symptomatic deterioration of lung function; if clinically indicated,
pulmonary function tests including measures of predicted lung volumes, diffusing
capacity of the lung for carbon monoxide (DLco), oxygen (O2) saturation at rest on
room air should be considered to exclude pneumonitis or pulmonary infiltrates
- Impairment of gastrointestinal (GI) function or GI disease that may significantly
alter the absorption of buparlisib (eg, ulcerative diseases, uncontrolled nausea,
vomiting, diarrhea, malabsorption syndrome, or small bowel resection); patients with
unresolved diarrhea will be excluded as previously indicated
- Patients who have been treated with any hematopoietic colony-stimulating growth
factors (eg, granulocyte-colony stimulating factor [G-CSF], granulocyte-macrophage
colony-stimulating factor [GM-CSF]) =< 2 weeks prior to starting study drug;
erythropoietin or darbepoetin therapy, if initiated at least 2 weeks prior to
enrollment, may be continued
- Patients who are currently receiving treatment with medication with a known risk to
prolong the QT interval or inducing Torsades de Pointes and the treatment cannot
either be discontinued or switched to a different medication prior to starting study
drug
- Patients receiving chronic treatment with steroids or another immunosuppressive agent
- Note: topical applications (eg, rash), inhaled sprays (eg, obstructive airways
diseases), eye drops or local injections (eg, intr-articular) are allowed;
patients with previously treated brain metastases, who are on stable low dose
corticosteriods treatment (eg, dexamethasone 2 mg/day, prednisolone 10 mg/day)
for at least 14 days before start of study treatment are eligible
- Patients who have taken herbal medications and certain fruits within 7 days prior to
starting study drug; herbal medications include, but are not limited to St. John's
Wort, Kava, ephedra (ma huang), dehydroepiandrosterone (DHEA), gingko biloba,
yohimbe, saw palmetto, and ginseng; fruits include the cytochrome P450, family 3,
subfamily A (CYP3A) inhibitors Seville oranges, grapefruit, pummelos, or exotic
citrus fruits
- Patients who are currently treated with drugs known to be moderate and strong
inhibitors or inducers of isoenzyme CYP3A, and the treatment cannot be discontinued
or switched to a different medication prior to starting study drug; please note that
co-treatment with weak inhibitors of CYP3A is allowed
- Patients who have received chemotherapy or targeted anticancer therapy =< 4 weeks (6
weeks for nitrosourea, antibodies or mitomycin-C) prior to starting study drug must
recover to a grade 1 before starting the trial
- Patients who have received any continuous or intermittent small molecule therapeutics
(excluding monoclonal antibodies) =< 5 effective half lives prior to starting study
drug or who have not recovered from side effects of such therapy
- Use of statin drugs or other medications known to associate with rhabdomyolysis;
these drugs must be discontinued at enrollment
- Patients who have received wide field radiotherapy =< 4 weeks or limited field
radiation for palliation =< 2 weeks prior to starting study drug or who have not
recovered from side effects of such therapy
- Patients who have undergone major surgery =< 2 weeks prior to starting study drug or
who have not recovered from side effects of such therapy
- Patients who are currently taking therapeutic doses of warfarin sodium or any other
coumadin-derivative anticoagulant; low molecular weight heparin is allowed
- Women who are pregnant or breast feeding or adults of reproductive potential not
employing an effective method of birth control; double barrier contraceptives must be
used through the trial by both sexes; oral, implantable, or injectable contraceptives
may be affected by cytochrome P450 interactions, and are therefore not considered
effective for this study; women of child-bearing potential, defined as sexually
mature women who have not undergone a hysterectomy or who have not been naturally
postmenopausal for at least 12 consecutive months (ie, who has had menses any time in
the preceding 12 consecutive months), must have a negative serum pregnancy test =< 72
hours prior to initiating treatment
- Women are considered post-menopausal and not of child bearing potential if they
have had 12 months of natural (spontaneous) amenorrhea with an appropriate
clinical profile (eg, age appropriate, history of vasomotor symptoms) or six
months of spontaneous amenorrhea with serum follicle stimulating hormone (FSH)
levels > 40 mIU/mL (for US only: and estradiol < 20 pg/mL) or have had surgical
bilateral oophorectomy (with or without hysterectomy) at least six weeks ago; in
the case of oophorectomy alone, only when the reproductive status of the woman
has been confirmed by follow up hormone level assessment is she considered not
of child bearing potential
- Women of child-bearing potential, defined as all women physiologically capable
of becoming pregnant, must use highly effective contraception during the study
and through 20 months after the final dose of study treatment; for males with
partners with childbearing potential, highly effective contraception is required
for 6 months; the highly effective contraception is defined as either:
- True abstinence: when this is in line with the preferred and usual
lifestyle of the subject; periodic abstinence (eg, calendar, ovulation,
symptothermal, post-ovulation methods) and withdrawal are not acceptable
methods of contraception
- Sterilization: have had surgical bilateral oophorectomy (with or without
hysterectomy) or tubal ligation at least six weeks ago; in case of
oophorectomy alone, only when the reproductive status of the woman has been
confirmed by follow up hormone level assessment
- Male partner sterilization (with the appropriate post-vasectomy
documentation of the absence of sperm in the ejaculate); for female
subjects on the study, the vasectomized male partner should be the sole
partner for that patient
- Use of a combination of any two of the following (a+b):
- a. Placement of an intrauterine device (IUD) or intrauterine system
(IUS)
- b. Barrier methods of contraception: condom or occlusive cap
(diaphragm or cervical/vault caps) with spermicidal
foam/gel/film/cream/vaginal suppository
- Oral contraception, injected or implanted hormonal methods are not allowed
- Fertile males, must use highly effective (double barrier) methods of
contraception (eg, spermicidal gel plus condom) for the entire duration of the
study, and continuing using contraception and refrain from fathering a child for
6 months following the study drug; a condom is required to be used also by
vasectomized men as well as during intercourse with a male partner in order to
prevent delivery of the study treatment via seminal fluid; female partner of
male study subject should use highly effective contraception during dosing of
any study agent and for 16 weeks after final dose of study therapy
- Note: hormonal contraception methods (eg, oral, injected, implanted) are not
allowed
- Note: woman are considered post-menopausal and not child bearing potential if
they have had 12 months of natural (spontaneous) amenorrhea with an appropriate
clinical profile (eg, age appropriate, history of vasomotor symptoms) or six
months of spontaneous amenorrhea with serum FSH levels > 40 mIU/mL and estradiol
< 20 pg/mL or have had surgical bilateral oophorectomy (with or without
hysterectomy) at least six weeks ago; in the case of oophorectomy alone, only
when the reproductive status of the woman has been confirmed by follow up
hormone level assessment is she considered not of child bearing potential
- Known diagnosis of human immunodeficiency virus (HIV) infection, hepatitis B or
hepatitis C
- History of another malignancy within 3 years, except cured basal cell carcinoma of
the skin or excised carcinoma in situ of the cervix
- Patient is unable or unwilling to abide by the study protocol or cooperate fully with
the investigator
Ages Eligible for Study
18 Years - N/A
Genders Eligible for Study
Both
Now accepting new patients
Contact Information
Primary Contact:
Anne Lynn Chang
650-721-7151
Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Erismodegib and Buparlisib in Treating Patients With Advanced or Metastatic Basal Cell Carcinoma
This pilot trial studies how well erismodegib and buparlisib work in treating patients withbasal cell carcinoma that has spread to other places in the body. Erismodegib and buparlisibmay stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Stanford is currently accepting patients for this trial. For more information, please contact Anne Lynn Chang at 650-721-7151 .
Lead Sponsor:
Stanford University
Collaborator: National Cancer Institute (NCI)
Stanford Investigator(s):
Intervention(s):
- Drug: buparlisib
- Drug: erismodegib
- Other: laboratory biomarker analysis
- Other: questionnaire administration
Phase:
N/A
Eligibility
Inclusion Criteria:
- Able to understand and sign informed consent
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Patients with metastatic BCC, histologic confirmation of distant BCC metastasis
- Patients with metastatic disease, target lesion must be measurable using computed
tomography (CT) or magnetic resonance imaging (MRI)
- Patients with locally advanced BCC are required to have disease that is considered
inoperable due to significant functional compromise or to have a medical
contraindication to surgery
- Patients with nevoid BCC syndrome (Gorlin syndrome) may enroll in this study but must
meet the criteria for locally advanced or metastatic disease listed above
- COHORT 2 ONLY: A Smoothened inhibitor must have been previously administered as
monotherapy
- Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
- Platelets >= 80 x10^9/L
- Hemoglobin (Hb) > 9 g/dL or values >= lower limit of normal (LLN) for site-specific
lab
- Total calcium (corrected for serum albumin) within normal limits (biphosphonate use
for malignant hypercalcemia control is not allowed)
- Magnesium >= the lower limit of normal
- Potassium within normal limits for the institution
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within normal
range (or =< 3.0 x upper limit of normal [ULN] if liver metastases are present)
- Serum bilirubin within normal range (or =< 1.5 x ULN if liver metastases are present;
or total bilirubin =< 3.0 x ULN with direct bilirubin within normal range in patients
with well-documented Gilbert Syndrome)
- Serum creatinine =< 1.5 x ULN or 24-hour clearance >= 50 mL/min
- Serum amylase =< ULN
- Serum lipase =< ULN
- Fasting plasma glucose =< 120 mg/dL (6.7 mmol/L)
- Negative serum pregnancy test within 72 hours before starting study treatment in
women with childbearing potential
- International normalized ratio (INR) =< 2
Exclusion Criteria:
- Patients who have received prior treatment with a P13K inhibitor
- Patients with a known hypersensitivity to buparlisib or to its excipients
- Patients with untreated brain metastases are excluded; however, patients with
metastatic central nervous system (CNS) tumors may participate in this trial, if the
patient is > 4 weeks from therapy completion (including radiation and/or surgery), is
clinically stable at the time of study entry and is not receiving corticosteroid
therapy
- Patients with acute or chronic liver, renal disease or pancreatitis
- Patients with baseline creatinine kinase (CK) > ULN
- Patients with the following mood disorders as judged by the Investigator or a
psychiatrist, or as a result of patient's mood assessment questionnaire:
- Medically documented history of or active major depressive episode, bipolar
disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of
suicidal attempt or ideation, or homicidal ideation (immediate risk of doing
harm to others)
- >= Common Terminology Criteria for Adverse Events (CTCAE) grade 3 anxiety
- Meets the cut-off score of >= 12 in the Patient Health Questionnaire (PHQ)-9 or
a cut-off of >= 15 in the Generalized Anxiety Disorder 7-item (GAD-7) mood
scale, respectively, or selects a positive response of "1, 2, or 3" to question
number 9 regarding potential for suicidal thoughts in the PHQ-9 (independent of
the total score of the PHQ-9)
- Patients with diarrhea >= CTCAE grade 2
- Patient has active cardiac disease including any of the following:
- Left ventricular ejection fraction (LVEF) < 50% as determined by multiple gated
acquisition (MUGA) scan or echocardiogram (ECHO)
- QTc > 450 msec on screening electrocardiogram (ECG) (using the QTcF formula)
- Angina pectoris that requires the use of anti-anginal medication
- Ventricular arrhythmias except for benign premature ventricular contractions
- Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled
with medication
- Conduction abnormality requiring a pacemaker
- Valvular disease with document compromise in cardiac function
- Symptomatic pericarditis
- Patient has a history of cardiac dysfunction including any of the following:
- Myocardial infraction within the last 6 months, documented by persistent
elevated cardiac enzymes or persistent regional wall abnormalities on assessment
of LVEF function
- History of documented congestive heart failure (New York Heart Association
functional classification III-IV)
- Documented cardiomyopathy
- Patient has poorly controlled diabetes mellitus (defined as hemoglobin A1C [HgA1c] >
ULN), steroid-induced diabetes mellitus or insulin dependent diabetes mellitus
- Other concurrent severe and/or uncontrolled concomitant medical conditions (eg,
active or uncontrolled infection) that could cause unacceptable safety risks or
compromise compliance with the protocol
- Significant symptomatic deterioration of lung function; if clinically indicated,
pulmonary function tests including measures of predicted lung volumes, diffusing
capacity of the lung for carbon monoxide (DLco), oxygen (O2) saturation at rest on
room air should be considered to exclude pneumonitis or pulmonary infiltrates
- Impairment of gastrointestinal (GI) function or GI disease that may significantly
alter the absorption of buparlisib (eg, ulcerative diseases, uncontrolled nausea,
vomiting, diarrhea, malabsorption syndrome, or small bowel resection); patients with
unresolved diarrhea will be excluded as previously indicated
- Patients who have been treated with any hematopoietic colony-stimulating growth
factors (eg, granulocyte-colony stimulating factor [G-CSF], granulocyte-macrophage
colony-stimulating factor [GM-CSF]) =< 2 weeks prior to starting study drug;
erythropoietin or darbepoetin therapy, if initiated at least 2 weeks prior to
enrollment, may be continued
- Patients who are currently receiving treatment with medication with a known risk to
prolong the QT interval or inducing Torsades de Pointes and the treatment cannot
either be discontinued or switched to a different medication prior to starting study
drug
- Patients receiving chronic treatment with steroids or another immunosuppressive agent
- Note: topical applications (eg, rash), inhaled sprays (eg, obstructive airways
diseases), eye drops or local injections (eg, intr-articular) are allowed;
patients with previously treated brain metastases, who are on stable low dose
corticosteriods treatment (eg, dexamethasone 2 mg/day, prednisolone 10 mg/day)
for at least 14 days before start of study treatment are eligible
- Patients who have taken herbal medications and certain fruits within 7 days prior to
starting study drug; herbal medications include, but are not limited to St. John's
Wort, Kava, ephedra (ma huang), dehydroepiandrosterone (DHEA), gingko biloba,
yohimbe, saw palmetto, and ginseng; fruits include the cytochrome P450, family 3,
subfamily A (CYP3A) inhibitors Seville oranges, grapefruit, pummelos, or exotic
citrus fruits
- Patients who are currently treated with drugs known to be moderate and strong
inhibitors or inducers of isoenzyme CYP3A, and the treatment cannot be discontinued
or switched to a different medication prior to starting study drug; please note that
co-treatment with weak inhibitors of CYP3A is allowed
- Patients who have received chemotherapy or targeted anticancer therapy =< 4 weeks (6
weeks for nitrosourea, antibodies or mitomycin-C) prior to starting study drug must
recover to a grade 1 before starting the trial
- Patients who have received any continuous or intermittent small molecule therapeutics
(excluding monoclonal antibodies) =< 5 effective half lives prior to starting study
drug or who have not recovered from side effects of such therapy
- Use of statin drugs or other medications known to associate with rhabdomyolysis;
these drugs must be discontinued at enrollment
- Patients who have received wide field radiotherapy =< 4 weeks or limited field
radiation for palliation =< 2 weeks prior to starting study drug or who have not
recovered from side effects of such therapy
- Patients who have undergone major surgery =< 2 weeks prior to starting study drug or
who have not recovered from side effects of such therapy
- Patients who are currently taking therapeutic doses of warfarin sodium or any other
coumadin-derivative anticoagulant; low molecular weight heparin is allowed
- Women who are pregnant or breast feeding or adults of reproductive potential not
employing an effective method of birth control; double barrier contraceptives must be
used through the trial by both sexes; oral, implantable, or injectable contraceptives
may be affected by cytochrome P450 interactions, and are therefore not considered
effective for this study; women of child-bearing potential, defined as sexually
mature women who have not undergone a hysterectomy or who have not been naturally
postmenopausal for at least 12 consecutive months (ie, who has had menses any time in
the preceding 12 consecutive months), must have a negative serum pregnancy test =< 72
hours prior to initiating treatment
- Women are considered post-menopausal and not of child bearing potential if they
have had 12 months of natural (spontaneous) amenorrhea with an appropriate
clinical profile (eg, age appropriate, history of vasomotor symptoms) or six
months of spontaneous amenorrhea with serum follicle stimulating hormone (FSH)
levels > 40 mIU/mL (for US only: and estradiol < 20 pg/mL) or have had surgical
bilateral oophorectomy (with or without hysterectomy) at least six weeks ago; in
the case of oophorectomy alone, only when the reproductive status of the woman
has been confirmed by follow up hormone level assessment is she considered not
of child bearing potential
- Women of child-bearing potential, defined as all women physiologically capable
of becoming pregnant, must use highly effective contraception during the study
and through 20 months after the final dose of study treatment; for males with
partners with childbearing potential, highly effective contraception is required
for 6 months; the highly effective contraception is defined as either:
- True abstinence: when this is in line with the preferred and usual
lifestyle of the subject; periodic abstinence (eg, calendar, ovulation,
symptothermal, post-ovulation methods) and withdrawal are not acceptable
methods of contraception
- Sterilization: have had surgical bilateral oophorectomy (with or without
hysterectomy) or tubal ligation at least six weeks ago; in case of
oophorectomy alone, only when the reproductive status of the woman has been
confirmed by follow up hormone level assessment
- Male partner sterilization (with the appropriate post-vasectomy
documentation of the absence of sperm in the ejaculate); for female
subjects on the study, the vasectomized male partner should be the sole
partner for that patient
- Use of a combination of any two of the following (a+b):
- a. Placement of an intrauterine device (IUD) or intrauterine system
(IUS)
- b. Barrier methods of contraception: condom or occlusive cap
(diaphragm or cervical/vault caps) with spermicidal
foam/gel/film/cream/vaginal suppository
- Oral contraception, injected or implanted hormonal methods are not allowed
- Fertile males, must use highly effective (double barrier) methods of
contraception (eg, spermicidal gel plus condom) for the entire duration of the
study, and continuing using contraception and refrain from fathering a child for
6 months following the study drug; a condom is required to be used also by
vasectomized men as well as during intercourse with a male partner in order to
prevent delivery of the study treatment via seminal fluid; female partner of
male study subject should use highly effective contraception during dosing of
any study agent and for 16 weeks after final dose of study therapy
- Note: hormonal contraception methods (eg, oral, injected, implanted) are not
allowed
- Note: woman are considered post-menopausal and not child bearing potential if
they have had 12 months of natural (spontaneous) amenorrhea with an appropriate
clinical profile (eg, age appropriate, history of vasomotor symptoms) or six
months of spontaneous amenorrhea with serum FSH levels > 40 mIU/mL and estradiol
< 20 pg/mL or have had surgical bilateral oophorectomy (with or without
hysterectomy) at least six weeks ago; in the case of oophorectomy alone, only
when the reproductive status of the woman has been confirmed by follow up
hormone level assessment is she considered not of child bearing potential
- Known diagnosis of human immunodeficiency virus (HIV) infection, hepatitis B or
hepatitis C
- History of another malignancy within 3 years, except cured basal cell carcinoma of
the skin or excised carcinoma in situ of the cervix
- Patient is unable or unwilling to abide by the study protocol or cooperate fully with
the investigator
Ages Eligible for Study
18 Years - N/A
Genders Eligible for Study
Both
Now accepting new patients
Contact Information
Primary Contact:
Anne Lynn Chang
650-721-7151
Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Erismodegib and Buparlisib in Treating Patients With Advanced or Metastatic Basal Cell Carcinoma
This pilot trial studies how well erismodegib and buparlisib work in treating patients withbasal cell carcinoma that has spread to other places in the body. Erismodegib and buparlisibmay stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Stanford is currently accepting patients for this trial. For more information, please contact Anne Lynn Chang at 650-721-7151 .
Lead Sponsor:
Stanford University
Collaborator: National Cancer Institute (NCI)
Stanford Investigator(s):
Intervention(s):
- Drug: buparlisib
- Drug: erismodegib
- Other: laboratory biomarker analysis
- Other: questionnaire administration
Phase:
N/A
Eligibility
Inclusion Criteria:
- Able to understand and sign informed consent
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Patients with metastatic BCC, histologic confirmation of distant BCC metastasis
- Patients with metastatic disease, target lesion must be measurable using computed
tomography (CT) or magnetic resonance imaging (MRI)
- Patients with locally advanced BCC are required to have disease that is considered
inoperable due to significant functional compromise or to have a medical
contraindication to surgery
- Patients with nevoid BCC syndrome (Gorlin syndrome) may enroll in this study but must
meet the criteria for locally advanced or metastatic disease listed above
- COHORT 2 ONLY: A Smoothened inhibitor must have been previously administered as
monotherapy
- Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
- Platelets >= 80 x10^9/L
- Hemoglobin (Hb) > 9 g/dL or values >= lower limit of normal (LLN) for site-specific
lab
- Total calcium (corrected for serum albumin) within normal limits (biphosphonate use
for malignant hypercalcemia control is not allowed)
- Magnesium >= the lower limit of normal
- Potassium within normal limits for the institution
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within normal
range (or =< 3.0 x upper limit of normal [ULN] if liver metastases are present)
- Serum bilirubin within normal range (or =< 1.5 x ULN if liver metastases are present;
or total bilirubin =< 3.0 x ULN with direct bilirubin within normal range in patients
with well-documented Gilbert Syndrome)
- Serum creatinine =< 1.5 x ULN or 24-hour clearance >= 50 mL/min
- Serum amylase =< ULN
- Serum lipase =< ULN
- Fasting plasma glucose =< 120 mg/dL (6.7 mmol/L)
- Negative serum pregnancy test within 72 hours before starting study treatment in
women with childbearing potential
- International normalized ratio (INR) =< 2
Exclusion Criteria:
- Patients who have received prior treatment with a P13K inhibitor
- Patients with a known hypersensitivity to buparlisib or to its excipients
- Patients with untreated brain metastases are excluded; however, patients with
metastatic central nervous system (CNS) tumors may participate in this trial, if the
patient is > 4 weeks from therapy completion (including radiation and/or surgery), is
clinically stable at the time of study entry and is not receiving corticosteroid
therapy
- Patients with acute or chronic liver, renal disease or pancreatitis
- Patients with baseline creatinine kinase (CK) > ULN
- Patients with the following mood disorders as judged by the Investigator or a
psychiatrist, or as a result of patient's mood assessment questionnaire:
- Medically documented history of or active major depressive episode, bipolar
disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of
suicidal attempt or ideation, or homicidal ideation (immediate risk of doing
harm to others)
- >= Common Terminology Criteria for Adverse Events (CTCAE) grade 3 anxiety
- Meets the cut-off score of >= 12 in the Patient Health Questionnaire (PHQ)-9 or
a cut-off of >= 15 in the Generalized Anxiety Disorder 7-item (GAD-7) mood
scale, respectively, or selects a positive response of "1, 2, or 3" to question
number 9 regarding potential for suicidal thoughts in the PHQ-9 (independent of
the total score of the PHQ-9)
- Patients with diarrhea >= CTCAE grade 2
- Patient has active cardiac disease including any of the following:
- Left ventricular ejection fraction (LVEF) < 50% as determined by multiple gated
acquisition (MUGA) scan or echocardiogram (ECHO)
- QTc > 450 msec on screening electrocardiogram (ECG) (using the QTcF formula)
- Angina pectoris that requires the use of anti-anginal medication
- Ventricular arrhythmias except for benign premature ventricular contractions
- Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled
with medication
- Conduction abnormality requiring a pacemaker
- Valvular disease with document compromise in cardiac function
- Symptomatic pericarditis
- Patient has a history of cardiac dysfunction including any of the following:
- Myocardial infraction within the last 6 months, documented by persistent
elevated cardiac enzymes or persistent regional wall abnormalities on assessment
of LVEF function
- History of documented congestive heart failure (New York Heart Association
functional classification III-IV)
- Documented cardiomyopathy
- Patient has poorly controlled diabetes mellitus (defined as hemoglobin A1C [HgA1c] >
ULN), steroid-induced diabetes mellitus or insulin dependent diabetes mellitus
- Other concurrent severe and/or uncontrolled concomitant medical conditions (eg,
active or uncontrolled infection) that could cause unacceptable safety risks or
compromise compliance with the protocol
- Significant symptomatic deterioration of lung function; if clinically indicated,
pulmonary function tests including measures of predicted lung volumes, diffusing
capacity of the lung for carbon monoxide (DLco), oxygen (O2) saturation at rest on
room air should be considered to exclude pneumonitis or pulmonary infiltrates
- Impairment of gastrointestinal (GI) function or GI disease that may significantly
alter the absorption of buparlisib (eg, ulcerative diseases, uncontrolled nausea,
vomiting, diarrhea, malabsorption syndrome, or small bowel resection); patients with
unresolved diarrhea will be excluded as previously indicated
- Patients who have been treated with any hematopoietic colony-stimulating growth
factors (eg, granulocyte-colony stimulating factor [G-CSF], granulocyte-macrophage
colony-stimulating factor [GM-CSF]) =< 2 weeks prior to starting study drug;
erythropoietin or darbepoetin therapy, if initiated at least 2 weeks prior to
enrollment, may be continued
- Patients who are currently receiving treatment with medication with a known risk to
prolong the QT interval or inducing Torsades de Pointes and the treatment cannot
either be discontinued or switched to a different medication prior to starting study
drug
- Patients receiving chronic treatment with steroids or another immunosuppressive agent
- Note: topical applications (eg, rash), inhaled sprays (eg, obstructive airways
diseases), eye drops or local injections (eg, intr-articular) are allowed;
patients with previously treated brain metastases, who are on stable low dose
corticosteriods treatment (eg, dexamethasone 2 mg/day, prednisolone 10 mg/day)
for at least 14 days before start of study treatment are eligible
- Patients who have taken herbal medications and certain fruits within 7 days prior to
starting study drug; herbal medications include, but are not limited to St. John's
Wort, Kava, ephedra (ma huang), dehydroepiandrosterone (DHEA), gingko biloba,
yohimbe, saw palmetto, and ginseng; fruits include the cytochrome P450, family 3,
subfamily A (CYP3A) inhibitors Seville oranges, grapefruit, pummelos, or exotic
citrus fruits
- Patients who are currently treated with drugs known to be moderate and strong
inhibitors or inducers of isoenzyme CYP3A, and the treatment cannot be discontinued
or switched to a different medication prior to starting study drug; please note that
co-treatment with weak inhibitors of CYP3A is allowed
- Patients who have received chemotherapy or targeted anticancer therapy =< 4 weeks (6
weeks for nitrosourea, antibodies or mitomycin-C) prior to starting study drug must
recover to a grade 1 before starting the trial
- Patients who have received any continuous or intermittent small molecule therapeutics
(excluding monoclonal antibodies) =< 5 effective half lives prior to starting study
drug or who have not recovered from side effects of such therapy
- Use of statin drugs or other medications known to associate with rhabdomyolysis;
these drugs must be discontinued at enrollment
- Patients who have received wide field radiotherapy =< 4 weeks or limited field
radiation for palliation =< 2 weeks prior to starting study drug or who have not
recovered from side effects of such therapy
- Patients who have undergone major surgery =< 2 weeks prior to starting study drug or
who have not recovered from side effects of such therapy
- Patients who are currently taking therapeutic doses of warfarin sodium or any other
coumadin-derivative anticoagulant; low molecular weight heparin is allowed
- Women who are pregnant or breast feeding or adults of reproductive potential not
employing an effective method of birth control; double barrier contraceptives must be
used through the trial by both sexes; oral, implantable, or injectable contraceptives
may be affected by cytochrome P450 interactions, and are therefore not considered
effective for this study; women of child-bearing potential, defined as sexually
mature women who have not undergone a hysterectomy or who have not been naturally
postmenopausal for at least 12 consecutive months (ie, who has had menses any time in
the preceding 12 consecutive months), must have a negative serum pregnancy test =< 72
hours prior to initiating treatment
- Women are considered post-menopausal and not of child bearing potential if they
have had 12 months of natural (spontaneous) amenorrhea with an appropriate
clinical profile (eg, age appropriate, history of vasomotor symptoms) or six
months of spontaneous amenorrhea with serum follicle stimulating hormone (FSH)
levels > 40 mIU/mL (for US only: and estradiol < 20 pg/mL) or have had surgical
bilateral oophorectomy (with or without hysterectomy) at least six weeks ago; in
the case of oophorectomy alone, only when the reproductive status of the woman
has been confirmed by follow up hormone level assessment is she considered not
of child bearing potential
- Women of child-bearing potential, defined as all women physiologically capable
of becoming pregnant, must use highly effective contraception during the study
and through 20 months after the final dose of study treatment; for males with
partners with childbearing potential, highly effective contraception is required
for 6 months; the highly effective contraception is defined as either:
- True abstinence: when this is in line with the preferred and usual
lifestyle of the subject; periodic abstinence (eg, calendar, ovulation,
symptothermal, post-ovulation methods) and withdrawal are not acceptable
methods of contraception
- Sterilization: have had surgical bilateral oophorectomy (with or without
hysterectomy) or tubal ligation at least six weeks ago; in case of
oophorectomy alone, only when the reproductive status of the woman has been
confirmed by follow up hormone level assessment
- Male partner sterilization (with the appropriate post-vasectomy
documentation of the absence of sperm in the ejaculate); for female
subjects on the study, the vasectomized male partner should be the sole
partner for that patient
- Use of a combination of any two of the following (a+b):
- a. Placement of an intrauterine device (IUD) or intrauterine system
(IUS)
- b. Barrier methods of contraception: condom or occlusive cap
(diaphragm or cervical/vault caps) with spermicidal
foam/gel/film/cream/vaginal suppository
- Oral contraception, injected or implanted hormonal methods are not allowed
- Fertile males, must use highly effective (double barrier) methods of
contraception (eg, spermicidal gel plus condom) for the entire duration of the
study, and continuing using contraception and refrain from fathering a child for
6 months following the study drug; a condom is required to be used also by
vasectomized men as well as during intercourse with a male partner in order to
prevent delivery of the study treatment via seminal fluid; female partner of
male study subject should use highly effective contraception during dosing of
any study agent and for 16 weeks after final dose of study therapy
- Note: hormonal contraception methods (eg, oral, injected, implanted) are not
allowed
- Note: woman are considered post-menopausal and not child bearing potential if
they have had 12 months of natural (spontaneous) amenorrhea with an appropriate
clinical profile (eg, age appropriate, history of vasomotor symptoms) or six
months of spontaneous amenorrhea with serum FSH levels > 40 mIU/mL and estradiol
< 20 pg/mL or have had surgical bilateral oophorectomy (with or without
hysterectomy) at least six weeks ago; in the case of oophorectomy alone, only
when the reproductive status of the woman has been confirmed by follow up
hormone level assessment is she considered not of child bearing potential
- Known diagnosis of human immunodeficiency virus (HIV) infection, hepatitis B or
hepatitis C
- History of another malignancy within 3 years, except cured basal cell carcinoma of
the skin or excised carcinoma in situ of the cervix
- Patient is unable or unwilling to abide by the study protocol or cooperate fully with
the investigator
Ages Eligible for Study
18 Years - N/A
Genders Eligible for Study
Both
Now accepting new patients
Contact Information
Primary Contact:
Anne Lynn Chang
650-721-7151
Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Erismodegib and Buparlisib in Treating Patients With Advanced or Metastatic Basal Cell Carcinoma
This pilot trial studies how well erismodegib and buparlisib work in treating patients withbasal cell carcinoma that has spread to other places in the body. Erismodegib and buparlisibmay stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Stanford is currently accepting patients for this trial. For more information, please contact Anne Lynn Chang at 650-721-7151 .
Lead Sponsor:
Stanford University
Collaborator: National Cancer Institute (NCI)
Stanford Investigator(s):
Intervention(s):
- Drug: buparlisib
- Drug: erismodegib
- Other: laboratory biomarker analysis
- Other: questionnaire administration
Phase:
N/A
Eligibility
Inclusion Criteria:
- Able to understand and sign informed consent
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Patients with metastatic BCC, histologic confirmation of distant BCC metastasis
- Patients with metastatic disease, target lesion must be measurable using computed
tomography (CT) or magnetic resonance imaging (MRI)
- Patients with locally advanced BCC are required to have disease that is considered
inoperable due to significant functional compromise or to have a medical
contraindication to surgery
- Patients with nevoid BCC syndrome (Gorlin syndrome) may enroll in this study but must
meet the criteria for locally advanced or metastatic disease listed above
- COHORT 2 ONLY: A Smoothened inhibitor must have been previously administered as
monotherapy
- Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
- Platelets >= 80 x10^9/L
- Hemoglobin (Hb) > 9 g/dL or values >= lower limit of normal (LLN) for site-specific
lab
- Total calcium (corrected for serum albumin) within normal limits (biphosphonate use
for malignant hypercalcemia control is not allowed)
- Magnesium >= the lower limit of normal
- Potassium within normal limits for the institution
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within normal
range (or =< 3.0 x upper limit of normal [ULN] if liver metastases are present)
- Serum bilirubin within normal range (or =< 1.5 x ULN if liver metastases are present;
or total bilirubin =< 3.0 x ULN with direct bilirubin within normal range in patients
with well-documented Gilbert Syndrome)
- Serum creatinine =< 1.5 x ULN or 24-hour clearance >= 50 mL/min
- Serum amylase =< ULN
- Serum lipase =< ULN
- Fasting plasma glucose =< 120 mg/dL (6.7 mmol/L)
- Negative serum pregnancy test within 72 hours before starting study treatment in
women with childbearing potential
- International normalized ratio (INR) =< 2
Exclusion Criteria:
- Patients who have received prior treatment with a P13K inhibitor
- Patients with a known hypersensitivity to buparlisib or to its excipients
- Patients with untreated brain metastases are excluded; however, patients with
metastatic central nervous system (CNS) tumors may participate in this trial, if the
patient is > 4 weeks from therapy completion (including radiation and/or surgery), is
clinically stable at the time of study entry and is not receiving corticosteroid
therapy
- Patients with acute or chronic liver, renal disease or pancreatitis
- Patients with baseline creatinine kinase (CK) > ULN
- Patients with the following mood disorders as judged by the Investigator or a
psychiatrist, or as a result of patient's mood assessment questionnaire:
- Medically documented history of or active major depressive episode, bipolar
disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of
suicidal attempt or ideation, or homicidal ideation (immediate risk of doing
harm to others)
- >= Common Terminology Criteria for Adverse Events (CTCAE) grade 3 anxiety
- Meets the cut-off score of >= 12 in the Patient Health Questionnaire (PHQ)-9 or
a cut-off of >= 15 in the Generalized Anxiety Disorder 7-item (GAD-7) mood
scale, respectively, or selects a positive response of "1, 2, or 3" to question
number 9 regarding potential for suicidal thoughts in the PHQ-9 (independent of
the total score of the PHQ-9)
- Patients with diarrhea >= CTCAE grade 2
- Patient has active cardiac disease including any of the following:
- Left ventricular ejection fraction (LVEF) < 50% as determined by multiple gated
acquisition (MUGA) scan or echocardiogram (ECHO)
- QTc > 450 msec on screening electrocardiogram (ECG) (using the QTcF formula)
- Angina pectoris that requires the use of anti-anginal medication
- Ventricular arrhythmias except for benign premature ventricular contractions
- Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled
with medication
- Conduction abnormality requiring a pacemaker
- Valvular disease with document compromise in cardiac function
- Symptomatic pericarditis
- Patient has a history of cardiac dysfunction including any of the following:
- Myocardial infraction within the last 6 months, documented by persistent
elevated cardiac enzymes or persistent regional wall abnormalities on assessment
of LVEF function
- History of documented congestive heart failure (New York Heart Association
functional classification III-IV)
- Documented cardiomyopathy
- Patient has poorly controlled diabetes mellitus (defined as hemoglobin A1C [HgA1c] >
ULN), steroid-induced diabetes mellitus or insulin dependent diabetes mellitus
- Other concurrent severe and/or uncontrolled concomitant medical conditions (eg,
active or uncontrolled infection) that could cause unacceptable safety risks or
compromise compliance with the protocol
- Significant symptomatic deterioration of lung function; if clinically indicated,
pulmonary function tests including measures of predicted lung volumes, diffusing
capacity of the lung for carbon monoxide (DLco), oxygen (O2) saturation at rest on
room air should be considered to exclude pneumonitis or pulmonary infiltrates
- Impairment of gastrointestinal (GI) function or GI disease that may significantly
alter the absorption of buparlisib (eg, ulcerative diseases, uncontrolled nausea,
vomiting, diarrhea, malabsorption syndrome, or small bowel resection); patients with
unresolved diarrhea will be excluded as previously indicated
- Patients who have been treated with any hematopoietic colony-stimulating growth
factors (eg, granulocyte-colony stimulating factor [G-CSF], granulocyte-macrophage
colony-stimulating factor [GM-CSF]) =< 2 weeks prior to starting study drug;
erythropoietin or darbepoetin therapy, if initiated at least 2 weeks prior to
enrollment, may be continued
- Patients who are currently receiving treatment with medication with a known risk to
prolong the QT interval or inducing Torsades de Pointes and the treatment cannot
either be discontinued or switched to a different medication prior to starting study
drug
- Patients receiving chronic treatment with steroids or another immunosuppressive agent
- Note: topical applications (eg, rash), inhaled sprays (eg, obstructive airways
diseases), eye drops or local injections (eg, intr-articular) are allowed;
patients with previously treated brain metastases, who are on stable low dose
corticosteriods treatment (eg, dexamethasone 2 mg/day, prednisolone 10 mg/day)
for at least 14 days before start of study treatment are eligible
- Patients who have taken herbal medications and certain fruits within 7 days prior to
starting study drug; herbal medications include, but are not limited to St. John's
Wort, Kava, ephedra (ma huang), dehydroepiandrosterone (DHEA), gingko biloba,
yohimbe, saw palmetto, and ginseng; fruits include the cytochrome P450, family 3,
subfamily A (CYP3A) inhibitors Seville oranges, grapefruit, pummelos, or exotic
citrus fruits
- Patients who are currently treated with drugs known to be moderate and strong
inhibitors or inducers of isoenzyme CYP3A, and the treatment cannot be discontinued
or switched to a different medication prior to starting study drug; please note that
co-treatment with weak inhibitors of CYP3A is allowed
- Patients who have received chemotherapy or targeted anticancer therapy =< 4 weeks (6
weeks for nitrosourea, antibodies or mitomycin-C) prior to starting study drug must
recover to a grade 1 before starting the trial
- Patients who have received any continuous or intermittent small molecule therapeutics
(excluding monoclonal antibodies) =< 5 effective half lives prior to starting study
drug or who have not recovered from side effects of such therapy
- Use of statin drugs or other medications known to associate with rhabdomyolysis;
these drugs must be discontinued at enrollment
- Patients who have received wide field radiotherapy =< 4 weeks or limited field
radiation for palliation =< 2 weeks prior to starting study drug or who have not
recovered from side effects of such therapy
- Patients who have undergone major surgery =< 2 weeks prior to starting study drug or
who have not recovered from side effects of such therapy
- Patients who are currently taking therapeutic doses of warfarin sodium or any other
coumadin-derivative anticoagulant; low molecular weight heparin is allowed
- Women who are pregnant or breast feeding or adults of reproductive potential not
employing an effective method of birth control; double barrier contraceptives must be
used through the trial by both sexes; oral, implantable, or injectable contraceptives
may be affected by cytochrome P450 interactions, and are therefore not considered
effective for this study; women of child-bearing potential, defined as sexually
mature women who have not undergone a hysterectomy or who have not been naturally
postmenopausal for at least 12 consecutive months (ie, who has had menses any time in
the preceding 12 consecutive months), must have a negative serum pregnancy test =< 72
hours prior to initiating treatment
- Women are considered post-menopausal and not of child bearing potential if they
have had 12 months of natural (spontaneous) amenorrhea with an appropriate
clinical profile (eg, age appropriate, history of vasomotor symptoms) or six
months of spontaneous amenorrhea with serum follicle stimulating hormone (FSH)
levels > 40 mIU/mL (for US only: and estradiol < 20 pg/mL) or have had surgical
bilateral oophorectomy (with or without hysterectomy) at least six weeks ago; in
the case of oophorectomy alone, only when the reproductive status of the woman
has been confirmed by follow up hormone level assessment is she considered not
of child bearing potential
- Women of child-bearing potential, defined as all women physiologically capable
of becoming pregnant, must use highly effective contraception during the study
and through 20 months after the final dose of study treatment; for males with
partners with childbearing potential, highly effective contraception is required
for 6 months; the highly effective contraception is defined as either:
- True abstinence: when this is in line with the preferred and usual
lifestyle of the subject; periodic abstinence (eg, calendar, ovulation,
symptothermal, post-ovulation methods) and withdrawal are not acceptable
methods of contraception
- Sterilization: have had surgical bilateral oophorectomy (with or without
hysterectomy) or tubal ligation at least six weeks ago; in case of
oophorectomy alone, only when the reproductive status of the woman has been
confirmed by follow up hormone level assessment
- Male partner sterilization (with the appropriate post-vasectomy
documentation of the absence of sperm in the ejaculate); for female
subjects on the study, the vasectomized male partner should be the sole
partner for that patient
- Use of a combination of any two of the following (a+b):
- a. Placement of an intrauterine device (IUD) or intrauterine system
(IUS)
- b. Barrier methods of contraception: condom or occlusive cap
(diaphragm or cervical/vault caps) with spermicidal
foam/gel/film/cream/vaginal suppository
- Oral contraception, injected or implanted hormonal methods are not allowed
- Fertile males, must use highly effective (double barrier) methods of
contraception (eg, spermicidal gel plus condom) for the entire duration of the
study, and continuing using contraception and refrain from fathering a child for
6 months following the study drug; a condom is required to be used also by
vasectomized men as well as during intercourse with a male partner in order to
prevent delivery of the study treatment via seminal fluid; female partner of
male study subject should use highly effective contraception during dosing of
any study agent and for 16 weeks after final dose of study therapy
- Note: hormonal contraception methods (eg, oral, injected, implanted) are not
allowed
- Note: woman are considered post-menopausal and not child bearing potential if
they have had 12 months of natural (spontaneous) amenorrhea with an appropriate
clinical profile (eg, age appropriate, history of vasomotor symptoms) or six
months of spontaneous amenorrhea with serum FSH levels > 40 mIU/mL and estradiol
< 20 pg/mL or have had surgical bilateral oophorectomy (with or without
hysterectomy) at least six weeks ago; in the case of oophorectomy alone, only
when the reproductive status of the woman has been confirmed by follow up
hormone level assessment is she considered not of child bearing potential
- Known diagnosis of human immunodeficiency virus (HIV) infection, hepatitis B or
hepatitis C
- History of another malignancy within 3 years, except cured basal cell carcinoma of
the skin or excised carcinoma in situ of the cervix
- Patient is unable or unwilling to abide by the study protocol or cooperate fully with
the investigator
Ages Eligible for Study
18 Years - N/A
Genders Eligible for Study
Both
Now accepting new patients
Contact Information
Primary Contact:
Anne Lynn Chang
650-721-7151
Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Erismodegib and Buparlisib in Treating Patients With Advanced or Metastatic Basal Cell Carcinoma
This pilot trial studies how well erismodegib and buparlisib work in treating patients withbasal cell carcinoma that has spread to other places in the body. Erismodegib and buparlisibmay stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Stanford is currently accepting patients for this trial. For more information, please contact Anne Lynn Chang at 650-721-7151 .
Lead Sponsor:
Stanford University
Collaborator: National Cancer Institute (NCI)
Stanford Investigator(s):
Intervention(s):
- Drug: buparlisib
- Drug: erismodegib
- Other: laboratory biomarker analysis
- Other: questionnaire administration
Phase:
N/A
Eligibility
Inclusion Criteria:
- Able to understand and sign informed consent
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Patients with metastatic BCC, histologic confirmation of distant BCC metastasis
- Patients with metastatic disease, target lesion must be measurable using computed
tomography (CT) or magnetic resonance imaging (MRI)
- Patients with locally advanced BCC are required to have disease that is considered
inoperable due to significant functional compromise or to have a medical
contraindication to surgery
- Patients with nevoid BCC syndrome (Gorlin syndrome) may enroll in this study but must
meet the criteria for locally advanced or metastatic disease listed above
- COHORT 2 ONLY: A Smoothened inhibitor must have been previously administered as
monotherapy
- Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
- Platelets >= 80 x10^9/L
- Hemoglobin (Hb) > 9 g/dL or values >= lower limit of normal (LLN) for site-specific
lab
- Total calcium (corrected for serum albumin) within normal limits (biphosphonate use
for malignant hypercalcemia control is not allowed)
- Magnesium >= the lower limit of normal
- Potassium within normal limits for the institution
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within normal
range (or =< 3.0 x upper limit of normal [ULN] if liver metastases are present)
- Serum bilirubin within normal range (or =< 1.5 x ULN if liver metastases are present;
or total bilirubin =< 3.0 x ULN with direct bilirubin within normal range in patients
with well-documented Gilbert Syndrome)
- Serum creatinine =< 1.5 x ULN or 24-hour clearance >= 50 mL/min
- Serum amylase =< ULN
- Serum lipase =< ULN
- Fasting plasma glucose =< 120 mg/dL (6.7 mmol/L)
- Negative serum pregnancy test within 72 hours before starting study treatment in
women with childbearing potential
- International normalized ratio (INR) =< 2
Exclusion Criteria:
- Patients who have received prior treatment with a P13K inhibitor
- Patients with a known hypersensitivity to buparlisib or to its excipients
- Patients with untreated brain metastases are excluded; however, patients with
metastatic central nervous system (CNS) tumors may participate in this trial, if the
patient is > 4 weeks from therapy completion (including radiation and/or surgery), is
clinically stable at the time of study entry and is not receiving corticosteroid
therapy
- Patients with acute or chronic liver, renal disease or pancreatitis
- Patients with baseline creatinine kinase (CK) > ULN
- Patients with the following mood disorders as judged by the Investigator or a
psychiatrist, or as a result of patient's mood assessment questionnaire:
- Medically documented history of or active major depressive episode, bipolar
disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of
suicidal attempt or ideation, or homicidal ideation (immediate risk of doing
harm to others)
- >= Common Terminology Criteria for Adverse Events (CTCAE) grade 3 anxiety
- Meets the cut-off score of >= 12 in the Patient Health Questionnaire (PHQ)-9 or
a cut-off of >= 15 in the Generalized Anxiety Disorder 7-item (GAD-7) mood
scale, respectively, or selects a positive response of "1, 2, or 3" to question
number 9 regarding potential for suicidal thoughts in the PHQ-9 (independent of
the total score of the PHQ-9)
- Patients with diarrhea >= CTCAE grade 2
- Patient has active cardiac disease including any of the following:
- Left ventricular ejection fraction (LVEF) < 50% as determined by multiple gated
acquisition (MUGA) scan or echocardiogram (ECHO)
- QTc > 450 msec on screening electrocardiogram (ECG) (using the QTcF formula)
- Angina pectoris that requires the use of anti-anginal medication
- Ventricular arrhythmias except for benign premature ventricular contractions
- Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled
with medication
- Conduction abnormality requiring a pacemaker
- Valvular disease with document compromise in cardiac function
- Symptomatic pericarditis
- Patient has a history of cardiac dysfunction including any of the following:
- Myocardial infraction within the last 6 months, documented by persistent
elevated cardiac enzymes or persistent regional wall abnormalities on assessment
of LVEF function
- History of documented congestive heart failure (New York Heart Association
functional classification III-IV)
- Documented cardiomyopathy
- Patient has poorly controlled diabetes mellitus (defined as hemoglobin A1C [HgA1c] >
ULN), steroid-induced diabetes mellitus or insulin dependent diabetes mellitus
- Other concurrent severe and/or uncontrolled concomitant medical conditions (eg,
active or uncontrolled infection) that could cause unacceptable safety risks or
compromise compliance with the protocol
- Significant symptomatic deterioration of lung function; if clinically indicated,
pulmonary function tests including measures of predicted lung volumes, diffusing
capacity of the lung for carbon monoxide (DLco), oxygen (O2) saturation at rest on
room air should be considered to exclude pneumonitis or pulmonary infiltrates
- Impairment of gastrointestinal (GI) function or GI disease that may significantly
alter the absorption of buparlisib (eg, ulcerative diseases, uncontrolled nausea,
vomiting, diarrhea, malabsorption syndrome, or small bowel resection); patients with
unresolved diarrhea will be excluded as previously indicated
- Patients who have been treated with any hematopoietic colony-stimulating growth
factors (eg, granulocyte-colony stimulating factor [G-CSF], granulocyte-macrophage
colony-stimulating factor [GM-CSF]) =< 2 weeks prior to starting study drug;
erythropoietin or darbepoetin therapy, if initiated at least 2 weeks prior to
enrollment, may be continued
- Patients who are currently receiving treatment with medication with a known risk to
prolong the QT interval or inducing Torsades de Pointes and the treatment cannot
either be discontinued or switched to a different medication prior to starting study
drug
- Patients receiving chronic treatment with steroids or another immunosuppressive agent
- Note: topical applications (eg, rash), inhaled sprays (eg, obstructive airways
diseases), eye drops or local injections (eg, intr-articular) are allowed;
patients with previously treated brain metastases, who are on stable low dose
corticosteriods treatment (eg, dexamethasone 2 mg/day, prednisolone 10 mg/day)
for at least 14 days before start of study treatment are eligible
- Patients who have taken herbal medications and certain fruits within 7 days prior to
starting study drug; herbal medications include, but are not limited to St. John's
Wort, Kava, ephedra (ma huang), dehydroepiandrosterone (DHEA), gingko biloba,
yohimbe, saw palmetto, and ginseng; fruits include the cytochrome P450, family 3,
subfamily A (CYP3A) inhibitors Seville oranges, grapefruit, pummelos, or exotic
citrus fruits
- Patients who are currently treated with drugs known to be moderate and strong
inhibitors or inducers of isoenzyme CYP3A, and the treatment cannot be discontinued
or switched to a different medication prior to starting study drug; please note that
co-treatment with weak inhibitors of CYP3A is allowed
- Patients who have received chemotherapy or targeted anticancer therapy =< 4 weeks (6
weeks for nitrosourea, antibodies or mitomycin-C) prior to starting study drug must
recover to a grade 1 before starting the trial
- Patients who have received any continuous or intermittent small molecule therapeutics
(excluding monoclonal antibodies) =< 5 effective half lives prior to starting study
drug or who have not recovered from side effects of such therapy
- Use of statin drugs or other medications known to associate with rhabdomyolysis;
these drugs must be discontinued at enrollment
- Patients who have received wide field radiotherapy =< 4 weeks or limited field
radiation for palliation =< 2 weeks prior to starting study drug or who have not
recovered from side effects of such therapy
- Patients who have undergone major surgery =< 2 weeks prior to starting study drug or
who have not recovered from side effects of such therapy
- Patients who are currently taking therapeutic doses of warfarin sodium or any other
coumadin-derivative anticoagulant; low molecular weight heparin is allowed
- Women who are pregnant or breast feeding or adults of reproductive potential not
employing an effective method of birth control; double barrier contraceptives must be
used through the trial by both sexes; oral, implantable, or injectable contraceptives
may be affected by cytochrome P450 interactions, and are therefore not considered
effective for this study; women of child-bearing potential, defined as sexually
mature women who have not undergone a hysterectomy or who have not been naturally
postmenopausal for at least 12 consecutive months (ie, who has had menses any time in
the preceding 12 consecutive months), must have a negative serum pregnancy test =< 72
hours prior to initiating treatment
- Women are considered post-menopausal and not of child bearing potential if they
have had 12 months of natural (spontaneous) amenorrhea with an appropriate
clinical profile (eg, age appropriate, history of vasomotor symptoms) or six
months of spontaneous amenorrhea with serum follicle stimulating hormone (FSH)
levels > 40 mIU/mL (for US only: and estradiol < 20 pg/mL) or have had surgical
bilateral oophorectomy (with or without hysterectomy) at least six weeks ago; in
the case of oophorectomy alone, only when the reproductive status of the woman
has been confirmed by follow up hormone level assessment is she considered not
of child bearing potential
- Women of child-bearing potential, defined as all women physiologically capable
of becoming pregnant, must use highly effective contraception during the study
and through 20 months after the final dose of study treatment; for males with
partners with childbearing potential, highly effective contraception is required
for 6 months; the highly effective contraception is defined as either:
- True abstinence: when this is in line with the preferred and usual
lifestyle of the subject; periodic abstinence (eg, calendar, ovulation,
symptothermal, post-ovulation methods) and withdrawal are not acceptable
methods of contraception
- Sterilization: have had surgical bilateral oophorectomy (with or without
hysterectomy) or tubal ligation at least six weeks ago; in case of
oophorectomy alone, only when the reproductive status of the woman has been
confirmed by follow up hormone level assessment
- Male partner sterilization (with the appropriate post-vasectomy
documentation of the absence of sperm in the ejaculate); for female
subjects on the study, the vasectomized male partner should be the sole
partner for that patient
- Use of a combination of any two of the following (a+b):
- a. Placement of an intrauterine device (IUD) or intrauterine system
(IUS)
- b. Barrier methods of contraception: condom or occlusive cap
(diaphragm or cervical/vault caps) with spermicidal
foam/gel/film/cream/vaginal suppository
- Oral contraception, injected or implanted hormonal methods are not allowed
- Fertile males, must use highly effective (double barrier) methods of
contraception (eg, spermicidal gel plus condom) for the entire duration of the
study, and continuing using contraception and refrain from fathering a child for
6 months following the study drug; a condom is required to be used also by
vasectomized men as well as during intercourse with a male partner in order to
prevent delivery of the study treatment via seminal fluid; female partner of
male study subject should use highly effective contraception during dosing of
any study agent and for 16 weeks after final dose of study therapy
- Note: hormonal contraception methods (eg, oral, injected, implanted) are not
allowed
- Note: woman are considered post-menopausal and not child bearing potential if
they have had 12 months of natural (spontaneous) amenorrhea with an appropriate
clinical profile (eg, age appropriate, history of vasomotor symptoms) or six
months of spontaneous amenorrhea with serum FSH levels > 40 mIU/mL and estradiol
< 20 pg/mL or have had surgical bilateral oophorectomy (with or without
hysterectomy) at least six weeks ago; in the case of oophorectomy alone, only
when the reproductive status of the woman has been confirmed by follow up
hormone level assessment is she considered not of child bearing potential
- Known diagnosis of human immunodeficiency virus (HIV) infection, hepatitis B or
hepatitis C
- History of another malignancy within 3 years, except cured basal cell carcinoma of
the skin or excised carcinoma in situ of the cervix
- Patient is unable or unwilling to abide by the study protocol or cooperate fully with
the investigator
Ages Eligible for Study
18 Years - N/A
Genders Eligible for Study
Both
Now accepting new patients
Contact Information
Primary Contact:
Anne Lynn Chang
650-721-7151
Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305