Ensayos clínicos

Inclusion Criteria:

• 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