This phase II trial is studying how well imatinib mesylate works in treating patients with stage III or stage IV melanoma that cannot be removed by surgery. Imatinib mesylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
PRIMARY OBJECTIVES: I. Determine the overall objective response rate (complete response and partial response) in patients with inoperable stage III or IV melanoma harboring somatic alterations in c-KIT treated with imatinib mesylate. SECONDARY OBJECTIVES: I. Determine the time to progression in patients treated with this drug. II. Determine if c-KIT mutational status by DNA sequencing, DNA copy number status by fluorescent in situ hybridization (FISH) or comparative genomic hybridization, and/or protein expression by immunohistochemistry (IHC) can best predict clinical benefit from imatinib mesylate. TERTIARY OBJECTIVES: I. To evaluate tumors resistant to small molecule inhibitors of Kit for the development of secondary Kit mutations or for changes in Kit copy number. II. To evaluate for changes in Ki-67, phospho-Akt, phospho-MEK, phospho-S6, phospho STAT3, cleaved caspase 3, IGF-1R, and Kit expression in paired tumor samples obtained from patients treated with a small molecule inhibitor of Kit. III. To analyze baseline and post-resistance blood samples for soluble cKIT levels, soluble VEGFR1, soluble VEGFR2, VEGF, PlGF, FGF, and melanoma inhibitory activity (MIA) levels, and circulating tumor cells. IV. To analyze concomitant samples of blood and tumor for imatinib levels in patients treated with imatinib. OUTLINE: This is a multi-center study. Patients are stratified according to true amplification of c-KIT by FISH vs mutations by DNA sequencing. Patients receive oral imatinib mesylate twice daily for up to 12 weeks in the absence of disease progression or unacceptable toxicity. Tumor tissue samples or unstained tissue slides/paraffin blocks may be collected. c-KIT is evaluated by IHC and comparative genomic hybridization. After completion of study treatment, patients are followed up periodically.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
30
Given orally
Correlative studies
University of California at Los Angeles (UCLA )
Los Angeles, California, United States
Mount Sinai Medical Center CCOP
Miami Beach, Florida, United States
Good Samaritan Medical Center
West Palm Beach, Florida, United States
Palm Beach Cancer Institute-Main Office
West Palm Beach, Florida, United States
New York University Langone Medical Center
New York, New York, United States
Mount Sinai Medical Center
New York, New York, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
Weill Medical College of Cornell University
New York, New York, United States
Objective Response Rate
Response will be evaluated in this study using the new international criteria proposed by the RECIST Committee. A Simon two-stage minimax design will be employed.
Time frame: Every 6 weeks for the first 3 courses and then every 12 weeks thereafter
Time to Progression
Progression will be evaluated in this study using the new international criteria proposed by the RECIST Committee. Time to progression will be estimated using the Kaplan-Meier method.
Time frame: Time from the treatment start to the date of disease progression
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