Vemurafenib Combined With Whole Brain Radiation Therapy or Radiosurgery in Patients With BRAF Mutation-Positive Melanoma and Brain Metastases

PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD) of vemurafenib when combined with WBRT or SRS and determine a recommended phase II dose of vemurafenib to be used with WBRT or SRS in patients with brain metastases from melanoma. SECONDARY OBJECTIVES: I. To determine local control rates of the brain metastases in each arm. II. To determine the rates of developing of new brain metastases in each arm. III. To determine the response of extracranial disease. IV. To determine the overall survival rate and progression free survival rate. V. To determine the safety and tolerability of each arm. OUTLINE: This is a dose-escalation study of vemurafenib. Patients are assigned to 1 of 2 arms based on the number and size of brain metastasis. All patients receive vemurafenib orally (PO) twice daily (BID) beginning 3-5 days before the start of radiation therapy and continuing in the absence of disease progression or unacceptable toxicity. ARM A: Patients undergo WBRT once daily (QD) for 10 doses. ARM B: Patients undergo SRS (gamma knife, tomotherapy, cyberknife, or megavoltage linear accelerator \[LINAC\] radiation therapy) on day 1. After completion of study therapy, patients are followed up on weeks 5 or 7, 9 and 13, and then on months 4, 6, 9, and 12.