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.