RATIONALE: Imatinib mesylate may interfere with the growth of tumor cells and may be an effective treatment for metastatic melanoma.

PURPOSE: Phase II trial to study the effectiveness of imatinib mesylate in treating patients who have metastatic melanoma.

OBJECTIVES:

• Determine the clinical activity of imatinib mesylate (STI571) in patients with metastatic melanoma.
• Determine the side effects of this drug in these patients.
• Correlate molecular studies with responsiveness to this drug in these patients.

OUTLINE: Patients receive oral imatinib mesylate (STI571) twice daily. Treatment continues in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 21-78 patients will be accrued for this study within 6-15 months.

• Kim KB, Eton O, Davis DW, Frazier ML, McConkey DJ, Diwan AH, Papadopoulos NE, Bedikian AY, Camacho LH, Ross MI, Cormier JN, Gershenwald JE, Lee JE, Mansfield PF, Billings LA, Ng CS, Charnsangavej C, Bar-Eli M, Johnson MM, Murgo AJ, Prieto VG. Phase II trial of imatinib mesylate in patients with metastatic melanoma. Br J Cancer. 2008 Sep 2;99(5):734-40. Epub 2008 Aug 19.
• Wyman K, Atkins MB, Prieto V, Eton O, McDermott DF, Hubbard F, Byrnes C, Sanders K, Sosman JA. Multicenter Phase II trial of high-dose imatinib mesylate in metastatic melanoma: significant toxicity with no clinical efficacy. Cancer. 2006 May 1;106(9):2005-11.

DISEASE CHARACTERISTICS:

• Histologically confirmed melanoma

• At least 20% of tumor cells with 1 of the following by immunohistochemistry:

  • Platelet-derived growth factor receptor alpha or beta
  • KIT (CD 117) expression documented by DAKO antibody staining c-abl, ARG

• At least 1 unidimensionally measurable metastatic target lesion, defined by 1 of the following:

  • At least 20 mm by conventional techniques
  • At least 10 mm by spiral CT scan
  • At least 10 mm for obviously visible cutaneous tumors
• Target lesions that have been previously embolized, perfused, or irradiated must have evidence of progression
• At least 1 metastatic lesion other than target lesion in subcutaneous site or lymph node that can be biopsied

• No symptomatic CNS metastases

  • Small asymptomatic CNS metastases allowed if no requirement for steroids exists and there is no associated significant edema
• No brain metastases as only site of disease

PATIENT CHARACTERISTICS:

Age:

• Any age

Performance status:

• ECOG 0-2 OR
• Karnofsky 60-100%

Life expectancy:

• Not specified

Hematopoietic:

• WBC at least 3,000/mm^3
• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 9 g/dL (transfusion allowed)

Hepatic:

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• AST/ALT no greater than 2.5 times ULN
• No uncontrolled chronic liver disease

Renal:

• Creatinine no greater than 1.5 times ULN
• No uncontrolled chronic renal disease

Cardiovascular:

• No symptomatic congestive heart failure
• No myocardial infarction within the past 2 months
• No unstable angina pectoris
• No cardiac arrhythmia

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective barrier contraception during and for 3 months after study entry
• No other concurrent severe and/or uncontrolled illness (e.g., uncontrolled diabetes)
• No active uncontrolled infection
• No psychiatric illness, social situation, or medical condition that would preclude study participation
• No other prior malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or other stage I or II cancer in complete remission

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• At least 4 weeks since prior biologic therapy

• Prior interferon therapy and/or one other systemic therapy regimen (e.g., chemotherapy, biotherapy, or biochemotherapy) allowed

  • Active immunotherapy (e.g., cancer vaccines) not included as systemic therapy regimen
• No concurrent anticancer biologic agents

Chemotherapy:

• See Biologic therapy
• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas)
• No concurrent chemotherapy

Endocrine therapy:

• See Disease Characteristics

Radiotherapy:

• See Disease Characteristics
• No concurrent radiotherapy

Surgery:

• At least 2 weeks since prior surgery

Other:

• Recovered from any prior therapy
• At least 28 days since prior investigational drugs
• No other concurrent anticancer agents
• No other concurrent investigational (i.e., non-approved) drugs
• No concurrent therapeutic doses of warfarin as anticoagulation therapy
• Concurrent therapeutic low-molecular weight heparin or other agents allowed
• Concurrent mini-dose warfarin (1 mg/day) as prophylaxis allowed