Principal Investigator
Enrollment Status
Clinical Trial ID
Clinical Trial Summary
This phase II trial studies how well vemurafenib and cobimetinib work in treating patients
with BRAF V600E mutation positive craniopharyngioma. Vemurafenib and cobimetinib may stop the
growth of tumor cells by blocking some of the enzymes needed for cell growth.
Phase
Phase 2
Funding Agency/Sponsor
National Cooperative Group
Disease
Neurological Cancer
Enrollment Eligibility
- Pre-registration: Patients must have local diagnosis of papillary craniopharyngioma
and have tissue slides available for submission to central pathology review; central
pathology review will include immunohistochemistry (IHC) testing for BRAF V600E
mutation (VE1 clone) and beta-catenin IHC (membranous, non-nuclear pattern) if needed
to confirm diagnosis of papillary craniopharyngioma
- Histologically proven papillary craniopharyngioma as documented by central pathology
review with positive BRAF V600E mutation by IHC
- Measurable disease and/or non-measurable disease
- Measurable disease, defined as bidimensionally measurable lesions with clearly
defined margins by magnetic resonance imaging (MRI) scans, with a minimum
diameter of 10 mm in both dimensions
- Progressive disease required in cohort B, defined as an increase in the
bidirectional area by 25% within the past 13 months after surgery or radiation;
progressive or recurrent disease is not required in cohort A, but is allowed
provided it is a new diagnosis and patient has not received prior treatment.
- Prior treatment
- Cohort A: No prior therapy received other than surgery
- Cohort B: Prior radiation therapy required (any type of prior radiation is
allowed)
- For patients treated with external beam radiation therapy, interstitial
brachytherapy or radiosurgery, an interval of >= 3 months must have elapsed
from completion of radiation therapy to registration
- Recovered to Common Terminology Criteria for Adverse Events (CTCAE) grade 1
or less toxicity attributed to radiation with exception of alopecia, fatigue
- For patients enrolling on Cohort A or Cohort B:
- For patients treated with surgery, an interval of >= 21 days must have
elapsed prior to registration
- No prior treatment with BRAF or MEK inhibitors
- Steroid dosing stable for at least 4 days prior to registration
- Not pregnant and not nursing; for women of childbearing potential only, a negative
pregnancy test done =< 7 days prior to registration is required
- ECOG performance status =< 2
- Comorbid conditions
- No evidence of active bleeding, bleeding diathesis, or hemoptysis (>= 1/2
teaspoon of red blood) =< 8 weeks prior to registration
- No evidence of intracranial hemorrhage =< 4 weeks prior to registration
- Patients who have experienced thromboembolic event within 6 months prior to
registration must be on stable therapeutic anticoagulation for at least 4 weeks
prior to registration
- No symptomatic congestive heart failure (New York Heart Association class II,
III, or IV) within 6 months prior to registration
- No current unstable angina or uncontrolled arrhythmia
- No uncontrolled hypertension at time of registration (blood pressure [BP] >
150/95 despite antihypertensive therapy)
- No known history of prolonged QT syndrome
- No known history of ventricular arrhythmia within 6 months of registration
- No known history of uveitis or iritis =< 4 weeks prior to registration
- No known history of or evidence of retinal pathology that is considered a risk
factor for neurosensory retinal detachment, retinal vein occlusion (RVO), or
neovascular macular degeneration within 12 months of registration
- No known history of chronic lung disease
- Concomitant medications
- Chronic concomitant treatment with strong CYP3A4 inducers or CYP3A4 inhibitors is
not allowed; patients must discontinue the drug at least 14 days prior to study
registration
- Chronic concomitant treatment with CYP1A2 substrate is not allowed; patients must
discontinue the drug at least 14 days prior to study registration
- Absolute neutrophil count >= 1500/mm^3
- Platelets >= 100,000/mm^3
- Creatinine =< 1.5 mg/dL OR creatinine clearance >= 45mL/min
- Bilirubin =< 1.5 upper limit of normal (ULN)
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 ULN