Vemurafenib and Cobimetinib in Treating Patients with BRAF V600E Mutation Positive Craniopharyngioma

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