RATIONALE: PI-88 may stop the growth of cancer by stopping blood flow to the tumor.

PURPOSE: Phase I/II trial to study the effectiveness of PI-88 in treating patients who have an advanced malignancy (cancer) or stage IV melanoma.

OBJECTIVES:

Phase I

• Determine the maximum tolerated dose of PI-88 in patients with an advanced malignancy.
• Determine the safety and tolerability of this drug in these patients.

Phase II

• Determine the progression-free survival and time to progression in patients with stage IV melanoma treated with this drug.
• Determine the biological activity of this drug in these patients.

OUTLINE: This is an open-label, dose-escalation study.

• Phase I (parts 1 and 2):

  • Part 1: Patients receive PI-88 subcutaneously (SC) once daily on days 1-4 and 15-18.

Cohorts of 3-6 patients receive escalating doses of PI-88 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD has been determined in part I, the effect of dose frequency is determined in patients in part II.

• Part 2: Patients receive PI-88 SC once daily on days 1-4, 8-11, 15-18, and 22-25 at a dose based on the MTD determined in part 1.

Cohorts of 3 patients receive escalating doses of PI-88 until the MTD at this frequency is determined.

• Phase II (patients with metastatic melanoma): Patients receive PI-88 as in phase I, part 2 at the MTD.

Treatment in both phases repeats every 28 days in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 18-69 patients (18-30 for phase I [part 1], 6-9 for phase I [part 2], and 25-30 for phase II) will be accrued for this study.

• Melanoma (Skin)
• Unspecified Adult Solid Tumor, Protocol Specific

DISEASE CHARACTERISTICS:

Phase I

• Histologically or cytologically confirmed malignancy
• No other effective treatment available OR failed prior therapy
• No prior or concurrent symptomatic or known CNS involvement or brain or meningeal metastases

Phase II

• Diagnosis of stage IV melanoma
• Metastatic disease must be measurable
• No other effective treatment available OR failed prior therapy
• Asymptomatic brain metastases allowed provided patient is off steroids

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2 OR
• Karnofsky 70-100%

Life expectancy

• At least 3 months

Hematopoietic

• Neutrophil count greater than 1,500/mm^3
• Platelet count greater than 100,000/mm^3
• Negative serotonin release assay test for anti-heparin antibodies
• No other abnormal bleeding tendency
• No history of heparin-induced thrombocytopenia
• No history of immune-mediated thrombocytopenia
• No history of thrombolytic thrombocytopenic purpura
• No history of other platelet disease

Hepatic

• Bilirubin less than 1.5 times upper limit of normal (ULN)
• AST and ALT no greater than 2 times ULN (5 times ULN if liver metastases are present)
• PTT normal (20-34 sec)
• PT less than 1.5 times ULN

Renal

• Creatinine clearance greater than 60 mL/min OR
• Glomerular filtration rate greater than 60 mL/min

Cardiovascular

• No myocardial infarction within the past 3 months
• No stroke within the past 3 months
• No congestive heart failure within the past 3 months

Gastrointestinal

• No history of acute or chronic gastrointestinal bleeding within the past 2 years
• No inflammatory bowel disease

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• HIV negative
• No AIDS-related illness
• No serious infection within the past 4 weeks
• No history of alcohol, drug, or other substance abuse
• No history of allergy and/or hypersensitivity to anti-coagulants/thrombolytic agents (e.g., heparin)
• No risk of bleeding due to open wounds or planned surgery
• No clinically significant nonmalignant disease
• No uncontrolled infection

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• More than 4 weeks since prior chemotherapy

Endocrine therapy

• More than 4 weeks since prior hormonal therapy

Radiotherapy

• More than 2 weeks since prior radiotherapy
• More than 4 weeks since prior radiotherapy to a major bone-marrow bearing area (e.g., pelvis, femoral heads, or lumbar-sacral spine)
• Concurrent palliative radiotherapy allowed

Surgery

• Recovered from prior major surgery
• No concurrent surgery

Other

• More than 2 weeks since prior heparin or low-molecular weight heparin
• More than 4 weeks since other prior investigational therapy
• No other concurrent investigational drugs
• No other concurrent antineoplastic therapy
• No concurrent aspirin or aspirin-containing medications

• No concurrent nonsteroidal anti-inflammatory drugs

  • Concurrent cyclooxygenase-2 inhibitors allowed
• No concurrent heparin or low-molecular weight heparin
• No concurrent warfarin or warfarin-containing medications
• No other concurrent anticoagulant medications