Pilot Efficacy Study of PI-88 With Docetaxel to Treat Prostate Cancer

• Status: Completed
• Trial end date: 2008-02-01
• Target enrollment: 0
• Participant gender: Male

Summary

Docetaxel (Taxotere) is an approved chemotherapeutic drug for the treatment of androgen-independent prostate cancer. The aim of the study is to investigate whether addition of the investigational drug PI-88 will increase the efficacy of docetaxel in this disease. PI-88 inhibits cancer growth by inhibiting the development of new blood vessels and starving the tumour of oxygen and nutrients (anti-angiogenic). Because PI-88 and docetaxel have different mechanisms of action, they are expected to have increased (synergistic) activity when combined.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Progen Pharmaceuticals
• Collaborators: Aventis Pharmaceuticals; Northern Sydney and Central Coast Area Health Service
• Treatments: Docetaxel; Prednisone

Criteria

Inclusion Criteria:

• Histologically/cytologically proven prostate adenocarcinoma that is unresponsive or refractory to hormone therapy

• Patients must have received prior hormonal therapy, defined as castration by orchiectomy and/or luteinizing hormone releasing hormone (LHRH) agonists

• Patients must have documented progression detected by PSA increase, physical examination and/or imaging

• Patients must have achieved stable pain control for a minimum of seven consecutive days prior to study entry.

• Prior radiation therapy (to < 25% of the bone marrow only) is permitted. At least 4 weeks must have elapsed since the completion of radiation therapy and the patient must have recovered from side effects prior to study entry.

• Prior surgery is allowed. At least 4 weeks must have elapsed since the completion of surgery

• Life expectancy > 3 months

• ECOG Performance score of < 2.

• Neutrophil count > 1.5 x 109/L (1,500/mm3)

• Haemoglobin > 10 g/dL

• Platelet count > 100 x 109/L (100,000/mm3)

• Total bilirubin < the upper limit of normal (ULN) of the institution

• ALT (SGPT) and AST (SGOT) < 1.5 x the ULN of the institution

• Calculated creatinine clearance, using Cockroft and Gault formula, >60 mL/min

• APTT and PT < 1.5 X ULN

• Patients (or legally acceptable representative) must have voluntarily given written informed consent to participate in this study.

• Patients must be willing to comply with the scheduled visit, treatment plans, laboratory tests, and other study procedures

Exclusion Criteria:

• Prior cytotoxic chemotherapy

• Prior isotope therapy (e.g., strontium, samarium)

• Prior radiotherapy to >25% of bone marrow (whole pelvic irradiation is not allowed)

• Prior treatment with biological response modifiers within the previous 4 weeks

• Prior malignancy except the following: adequately treated basal cell or squamous cell skin cancer, or any other cancer from which the patient has been disease-free for > 5 years

• Known brain or leptomeningeal involvement

• Symptomatic peripheral neuropathy > grade 2 according to the NCI Common Terminology Criteria for Adverse Events v3 (NCI CTCAE v3)

• Serious intercurrent medical illness that does not permit adequate follow-up and compliance with the study protocol

• History of immune-mediated thrombocytopenia, thrombotic thrombocytopenic purpura or other platelet disease, or laboratory evidence of anti-heparin antibodies

• Use of drugs that may inhibit the metabolism of docetaxel (cyclosporin, terfenadine, ketoconazole, erythromycin, troleandomycin) within the previous week or during the study

• Concurrent treatment with other experimental drugs. Participation in another clinical trial with any investigational drug within 30 days prior to study screening

• Treatment with any other anti-cancer therapy (except LHRH agonists) including any prescribed compounds and/or over-the-counter (OTC) products for the treatment of prostate cancer must be stopped prior to day of enrolment

• Treatment with systemic corticosteroids used for reasons other than specified by the protocol must be stopped prior to day of enrolment

• Concomitant bisphosphonate therapy is not allowed. Patients already receiving bisphosphonates must be stopped prior to day of enrolment

• Concomitant use of aspirin (> 150 mg/day), non-steroidal anti-inflammatory drugs (except specific COX-2 inhibitors), heparin, low molecular weight heparin (LMWH), 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

• Treatment with heparin or low molecular weight heparin within the previous two weeks is not permitted

• History of allergy and/or hypersensitivity to heparin or other anti-coagulants/thrombolytic agents

• History of acute or chronic gastrointestinal bleeding within the last two years, inflammatory bowel disease or other abnormal bleeding tendency

• Patients at risk of bleeding due to open wounds or planned surgery

• Myocardial infarction, stroke or congestive heart failure within the past three months

• Uncontrolled or serious infection within the past four weeks