A Phase II Study of Imatinib Mesylate (STI571;NSC#716051:IND 61135) in Patients With Inoperable AJCC Stage III or IV Melanoma Harboring Somatic Alterations of C-KIT
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.
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.
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.
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Objective response rate (complete response and partial response)
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.
Every 6 weeks for the first 3 courses and then every 12 weeks thereafter
Memorial Sloan-Kettering Cancer Center
United States: Food and Drug Administration
|Memorial Sloan Kettering Cancer Center||New York, New York 10021|
|Good Samaritan Medical Center||West Palm Beach, Florida 33401|
|Mount Sinai Medical Center||New York, New York 10029|