Trial of PI-88 With Dacarbazine in Patients With Metastatic Melanoma

Exclusion Criteria

• •PT \< 1.5 x upper limit of normal (ULN)
• •APTT \< 1.5 x ULN
• •Creatinine clearance \> 40 mL/min, calculated using the Cockcroft-Gault formula (if just below 40 mL/min, then GFR \> 40 mL/min as determined by 24-hour urine collection)
• •Current or history of central nervous system involvement, brain or meningeal metastases
• •Ocular melanoma
• •Clinically significant non-malignant disease
• •Prior or co-existent malignancies (other than stage I internal malignancy where treated and disease-free for \> 5 years, non-melanomatous skin cancer or in situ cancer of the cervix)
• •Prior chemotherapy
• •Prior treatment with vaccines and/or biological response modifiers within the previous 4 weeks
• •Prior treatment with radiotherapy within the previous 4 weeks (local palliative radiotherapy is permitted)
• •Radiotherapy to \> 30% of marrow-bearing bone within the previous 3 months
• •Major surgery within the past 4 weeks
• •Concomitant use of aspirin (\> 150 mg/day), non-steroidal anti-inflammatory drugs (except specific COX-2 inhibitors), heparin, low molecular weight heparin, warfarin (\> 1 mg/day) or anti-platelet drugs (abciximab, clopidogrel, dipyridamole, ticlopidine and tirofiban). Low-dose aspirin (≤ 150 mg/day) and low-dose warfarin (≤ 1 mg/day) are permitted as concomitant medications.
• •Heparin or low molecular weight heparin within the previous 2 weeks
• •History of acute or chronic gastrointestinal bleeding within the last 2 years, inflammatory bowel disease or other abnormal bleeding tendency
• •Patients at risk of bleeding due to open wounds or planned surgery
• •Bilirubin \> 1.5 x ULN
• •AST or ALT \> 3 x ULN unless patient has hepatic metastases
• •LDH \> 2 x ULN
• •Alkaline phosphatase \> 5 x ULN, unless patient has bone metastases
• •Myocardial infarction, stroke or congestive heart failure within the past 3 months
• •Women who are pregnant or breast feeding
• •Women of childbearing potential in whom pregnancy cannot be excluded or who are not using an adequate method of contraception
• •History of allergy and/or hypersensitivity to anti-coagulants/thrombolytic agents, especially heparin
• •History of immune-mediated thrombocytopenia, thrombotic thrombocytopenic purpura or other platelet disease, or laboratory evidence of anti-heparin antibodies
• •Uncontrolled or serious infection within the past 4 weeks
• •Patients who are unable to be compliant or to follow instructions given to them by clinic staff