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.

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