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

This study has been terminated.
(Lack of accrual)
Sponsor:
Collaborator:
Genentech
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT01474551
First received: November 15, 2011
Last updated: March 14, 2013
Last verified: March 2013
  Purpose

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.


Condition Intervention Phase
Melanoma
Drug: vemurafenib
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • overall objective response [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • effects of clinical benefit [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    i.e. improvement in performance and functional status). The effects on clinical benefit (changes in ECOG performance status, timed "up and go", Katz score of ADLs, and achievement of personal aspiration) will be reported but no formal statistical analysis is planned.

  • Time to progression and overall survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Time to progression and overall survival will be estimated using Kaplan-Meier methodology.

  • To assess toxicity [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    All adverse events encountered during the study will be evaluated according to the NCI Common Toxicity Grading system version 4.0.


Enrollment: 2
Study Start Date: November 2011
Study Completion Date: March 2013
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

Ages Eligible for Study:   19 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01474551

Locations
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Genentech
Investigators
Principal Investigator: Paul Chapman, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided by Memorial Sloan-Kettering Cancer Center

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT01474551     History of Changes
Other Study ID Numbers: 11-091
Study First Received: November 15, 2011
Last Updated: March 14, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Memorial Sloan-Kettering Cancer Center:
Vemurafenib
skin cancer
Stage IV
advanced stage III
11-091

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas

ClinicalTrials.gov processed this record on July 29, 2014