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

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

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.

Study Overview

• Status: Terminated
• Conditions: Melanoma
• Intervention / Treatment: Drug: vemurafenib

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: vemurafenib; 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; 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.

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

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborators: Genentech, Inc.

Publications and helpful links

General Publications

• Alloo A, Garibyan L, LeBoeuf N, Lin G, Werchniak A, Hodi FS Jr, Flaherty KT, Lawrence DP, Lin JY. Photodynamic therapy for multiple eruptive keratoacanthomas associated with vemurafenib treatment for metastatic melanoma. Arch Dermatol. 2012 Mar;148(3):363-6. doi: 10.1001/archdermatol.2011.3080.

Helpful Links

• Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (Actual): March 1, 2013
• Study Completion (Actual): March 1, 2013

Study Registration Dates

• First Submitted: November 15, 2011
• First Submitted That Met QC Criteria: November 17, 2011
• First Posted (Estimate): November 18, 2011

Study Record Updates

• Last Update Posted (Estimate): November 18, 2015
• Last Update Submitted That Met QC Criteria: October 20, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: skin cancer; Stage IV; Vemurafenib; advanced stage III; 11-091
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Vemurafenib
• Other Study ID Numbers: 11-091