ABT-510 in Treating Patients With Metastatic Melanoma

OBJECTIVES:

• Examine the safety profile of ABT-510 in patients with metastatic malignant melanoma.
• Examine the antitumor activity (i.e., time to progression and response rates) in patients treated with ABT-510.
• Determine the pharmacodynamic effects of ABT-510 and its potential impact on immune cell function in these patients.

OUTLINE: Patients receive ABT-510 subcutaneously twice daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Blood samples are obtained at baseline, before treatment on day 1 of cycles 2 and 3, and then every other course thereafter for pharmacological and ancillary studies. Samples are evaluated for EC enumeration, expression profiling, circulating tumor cell quantification, analysis of T-cell functions (i.e., immunophenotyping for NK-, T- and B-cell phenotypes as well as ELISPOT analysis against common environmental pathogens and T cell spectratyping), and angiogenesis bioassays. Patients also undergo ultrasound-guided core tumor biopsies for histological analysis of microvascular density (CD38 and von Willebrand Factor immunohistochemistry) at baseline and before treatment on day 1 of courses 3 and 5.

After completion of study treatment, patients are followed every 3 months for up to 5 years.

DISEASE CHARACTERISTICS:

• Histologically confirmed malignant melanoma

• Stage IV disease
• No known potentially curative standard therapy that exists or is proven capable of extending life expectancy
• Measurable disease
• No history of or current CNS metastases

• MRI of the brain to confirm absence of CNS metastases within the past 28 days is required
• No known, presently active carcinomatous meningitis

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Life expectancy ≥ 6 months
• ANC ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Alkaline phosphatase ≤ 3 times upper limit of normal (ULN)
• AST ≤ 3 times ULN
• Creatinine ≤ 2.5 times ULN
• Hemoglobin ≥ 9.0 g/dL
• Prothrombin time normal
• Willing to return to Mayo Clinic Rochester, Jacksonville or Scottsdale for follow-up
• Must be able to self-administer or has a caregiver who can reliably administer subcutaneous injections
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No uncontrolled or current infection
• No New York Heart Association class III-IV heart disease
• No recent history of (i.e., ≤ 12 weeks from study day 1) or current cancer-related bleeding event (e.g., hemoptysis)
• No recent history of (within the past 4 weeks) or current noncancer-related clinically significant bleeding event
• No uncontrolled hypertension
• No history of stroke or other CNS bleeding events (e.g., aneurysms)

PRIOR CONCURRENT THERAPY:

• At least 4 weeks since prior chemotherapy and recovered (6 weeks for mitomycin C or nitrosoureas)
• At least 4 weeks since prior immunotherapy, biologic therapy, radiotherapy, or surgery
• No concurrent anticoagulation therapy or antiplatelet therapy
• No other concurrent antineoplastic agents (e.g., cytotoxic chemotherapy, immunotherapy, radiotherapy, or investigational therapy) except local radiotherapy for supportive reasons involving a small radiation field