Phase 2 Study of Neoadjuvant Vemurafenib in Melanoma Patients With Untreated Brain Metastases

Inclusion Criteria:

* Biopsy proven metastatic melanoma with the B-raf V600E or V600K mutations.
* Untreated brain metastases
* At least one cerebral metastasis that is not amenable to stereotactic radiosurgery (SRS) or surgical resection based on size or location OR four or more lesions
* Patients may be symptomatic at the time of enrollment, but after any necessary local therapy and/or corticosteroids, the patient should be asymptomatic when vemurafenib is initiated.
* Age \>18
* Adequate organ function
* ECOG performance status \< 3
* No prior therapies with selective inhibitors of mutated BRAF; other prior therapies must have been administered at least 4 weeks before administration of vemurafenib
* Life expectancy of at least 3 months
* Understanding and willingness to consent
* The use of corticosteroids to control cerebral edema or treat symptoms will be allowed
* A history of whole brain radiotherapy for brain metastases is allowed, but any stable lesion that was present at the time of WBRT will NOT be considered evaluable. A minimum of 1 week break will be required between prior WBRT and initiation of vemurafenib therapy.

Exclusion Criteria:

* Presence of leptomeningeal disease based on positive CSF cytology.
* History or presence of clinically significant ventricular or atrial dysrhythmias ≥ Grade 2 (NCI CTCAE, v4.0), Corrected QT (QTc) interval \>450 ms at baseline or history of congenital long QT syndrome
* Uncontrolled medical illness, such as uncontrolled infection, congestive heart failure and MI within 2 months.
* Second active, untreated malignancy, which is likely to result in the patient's demise prior to death from uncontrolled melanoma CNS metastases. This will be determined on a case by case basis by the PIs.
* Unwillingness to undergo monitoring for a secondary malignancy including clinical dermatologic examinations and head and neck examinations and serial CT scans.