A Single Center Phase II Trial of Vemurafenib (R05185426) in Poor Performance Status Patients With Unresectable Locally Advanced or Metastatic Melanoma Harboring a V600E/K Mutation
- 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.
- 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
- 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.