Lack of accrual

The purpose of this study is to find out what effects, good and/or bad, vemurafenib has on the patient and the melanoma. Specifically, the investigators want to know how well vemurafenib shrinks melanoma. The investigators also want to find out how well vemurafenib can improve how well the patient functions.

Inclusion Criteria:

• Age >18 years old.
• Histologic proof of melanoma reviewed and confirmed by MSKCC.
• A confirmed EBRAFV600E or KBRAFV600K mutation.
• Stage IV melanoma, or advanced stage III not curable by surgery. Patients with active CNS metastases will be allowed on the study.
• Measurable disease by RECIST v1.1.
• ECOG performance status 3 or 4. The basis for the grading of performance is strict; there must be clear justification of the performance status grade (e.g. patient is confined to bed > 50% of time, or cannot carry out ADLs, or is otherwise disabled by burden of disease such as requiring supplemental O2).
• Patients must be able to swallow pills
• Adequate hematologic, hepatic and renal function as defined by the following:
• Absolute Neutrophil Count ≥ 1.0 x 109/L
• Hemoglobin ≥8.0g/dL, occasional transfusions are acceptable as vemurafenib does not have significant hematologic toxicities.
• Total bilirubin ≤2.0x the upper limit of normal, ≤3.0x the upper limit of normal if the patient has Gilbert's Syndrome.
• Alkaline phosphatase ≤2.0x the upper limit of normal.
• AST and ALT ≤2.0x the upper limit of normal.
• Serum creatinine ≤ 1.5x the upper limit of normal.

Exclusion Criteria:

• Uveal melanoma as primary.
• Concurrent chemotherapy, immunotherapy, or radiotherapy.
• Prior treatment with a RAF inhibitor. Other prior chemotherapy, immunotherapy, or radiotherapy will be allowed including prior treatment with a MEK inhibitor Patients must have had complete recovery from any adverse events or toxicities of prior cancer-directed therapies.
• Pregnant or lactating women.
• A second active malignancy. Prior malignancy will be allowed as long as the patient is known to be free of disease for at least 2 years. Patients with indolent B-cell malignancies will not be eligible.
• QTc interval > 500 msec.