Trial of PI-88 With Dacarbazine in Patients With Metastatic Melanoma
Condition: Melanoma
MeSH terms: Melanoma
Intervention: PI-88 and dacarbazine; dacarbazine or DTIC
Intervention description: 190 mg daily by subcutaneous injection for PI-88 and 1000 mg/m2 on day 1 of each 21 day cycle by intravenous infusion; intravenous infusion 1000 mg/m2 on day 1 of every 21 day cycle
Intervention MeSH terms: Dacarbazine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 134.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: phase II; metastatic melanoma; dacarbazine; combination; PI-88

Summary:

      The aim of the study is to compare the safety and effectiveness of a new drug called PI-88,
      when used in combination with an approved chemotherapy drug called dacarbazine, in the
      treatment of metastatic melanoma.

      PI-88 blocks new blood vessel growth in tumours (starves it of nutrients) and dacarbazine
      stops the cancer cells from growing. The results from this study will be analysed to see if
      it is worthwhile for the two drugs to be tested in future studies involving larger numbers of
      melanoma patients.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically proven metastatic melanoma

          -  Surgery not feasible or inappropriate

          -  Measurable disease. Metastatic lesions must be measurable by magnetic resonance
             imaging (MRI) or computed tomography (CT) as defined in Response Evaluation Criteria
             in Solid Tumors (RECIST), and cutaneous lesions by physical examination.

          -  Have voluntarily given written informed consent to participate in this study

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1

          -  Life expectancy at least 3 months

          -  Neutrophil count > 1.5 x 10^9/L (1,500/mm3)

          -  Platelet count > 100 x 10^9/L (100,000/mm3)

          -  Acceptable liver function tests (see Exclusion Criteria for maximum allowable
             elevations of ALT, AST, ALP and LDH)

          -  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)

        Exclusion Criteria:

          -  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