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
Overview
- Phase
- Phase 2
- Intervention
- imatinib mesylate
- Conditions
- Acral Lentiginous Malignant Melanoma
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 30
- Locations
- 8
- Primary Endpoint
- Objective Response Rate
- Status
- Completed
- Last Updated
- 11 years ago
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically or cytologically confirmed inoperable stage III or IV melanoma that began on acral skin or mucosa
- •Patients with cutaneous melanoma that began on sun exposed sites of the skin and whose pathology demonstrates signs of sun damage (solar elastosis) involving the skin surrounding their primary melanoma are eligible
- •Must have sufficient tumor tissue available for FISH and DNA sequencing
- •Patients must have either a true amplification of 4q12 or a detectable mutation of c-KIT
- •If no banked tumor tissue is available, or if the available banked tumor tissue is insufficient for the necessary testing, then a repeat biopsy procedure will be required to collect the necessary tumor sample
- •Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria
- •No known untreated brain or epidural metastases
- •Brain metastases that have been treated and deemed stable are allowed
- •ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
- •Life expectancy greater than 3 months
Exclusion Criteria
- Not provided
Arms & Interventions
Treatment (enzyme inhibitor therapy)
Patients receive oral imatinib mesylate twice daily for up to 12 weeks in the absence of disease progression or unacceptable toxicity.
Intervention: imatinib mesylate
Treatment (enzyme inhibitor therapy)
Patients receive oral imatinib mesylate twice daily for up to 12 weeks in the absence of disease progression or unacceptable toxicity.
Intervention: laboratory biomarker analysis
Outcomes
Primary Outcomes
Objective Response Rate
Time Frame: Every 6 weeks for the first 3 courses and then every 12 weeks thereafter
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.
Secondary Outcomes
- Time to Progression(Time from the treatment start to the date of disease progression)