Study on Vemurafenib and Cobimetinib for Treating Craniopharyngioma with BRAF V600E Mutation

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