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