Vemurafenib (R05185426) in Poor Performance Status Patients With Unresectable Locally Advanced or Metastatic Melanoma Harboring a V600E/K Mutation

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.