Phase II Trial of BRAF/MEK Inhibitors in Papillary Craniopharyngiomas

• 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