Vemurafenib (R05185426) in Poor Performance Status Patients With Unresectable Locally Advanced or Metastatic Melanoma Harboring a V600E/K Mutation
Condition: Melanoma
MeSH terms: Melanoma
Intervention: vemurafenib
Intervention description: All patients would be treated with vemurafenib given orally at 960 mg twice a day, which was the phase III dose. One cycle is 4 weeks long.
Intervention MeSH terms: Vemurafenib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 2.0
Sex: All
Minimum age: 19 Years
Healthy volunteers: No
Keywords: Vemurafenib; skin cancer; Stage IV; advanced stage III; 11-091

Summary:

      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.
    

Eligibility criteria:

        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.