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

Study Overview
=================
Brief 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.

Official Title
-----------------
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

Conditions
-----------------
Melanoma

Intervention / Treatment
-----------------
* Drug: vemurafenib


Participation Criteria
=================
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.

Ages Eligible for Study
-----------------
Minimum Age: 19 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: vemurafenib<br>This is a single institution phase II trial in stage III or IV melanoma patients with poor ECOG performance status (3 or 4). Patients must have melanoma with a BRAFV600E or BRAFV600K or mutation with measurable disease not curable by surgery. | Drug: vemurafenib<br>* 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.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Objective Response | The Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 will be used to determine treatment response. In order to be considered evaluable for response, a patient must have completed at least 1 cycle of therapy. Patients who do not complete a cycle of therapy can be replaced. | 2 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Vemurafenib, skin cancer, Stage IV, advanced stage III, 11-091