Clinical trial NCT01474551: Vemurafenib (R05185426) in Poor Performance Status Patients With Unresectable Locally Advanced or Metastatic Melanoma Harboring a V600E/K Mutation
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Melanoma
Keywords: Vemurafenib
skin cancer
Stage IV
advanced stage III
11-091
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
Collaborators: name: Genentech, Inc.
First posted: 2011-11-18
Enrollment: 2
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Overall Objective Response
timeFrame: 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Paul Chapman, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.