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A Randomised Phase II Study of Two Dose Schedules of PI-88 in Combination With Docetaxel in Patients With Androgen-independent Prostate Cancer

Phase 2
18 Years
Not Enrolling
Prostate Cancer

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Trial Information

A Randomised Phase II Study of Two Dose Schedules of PI-88 in Combination With Docetaxel in Patients With Androgen-independent Prostate Cancer

The trial is a multi-centre, open-label randomised phase II study in patients with
androgen-independent prostate cancer (AIPC), with a lead-in combination tolerance study. The
aim of the lead-in phase is to establish the maximum tolerated dose (MTD) of PI-88
administered either 4 days/week or 7 days/week) in combination with fixed doses of docetaxel
(75 mg/m^2 every 21 days) and prednisone (5 mg twice daily). In the randomized phase II
component, patients will receive PI-88 at the MTD, either 4 days/week or 7 days/week, in
combination with docetaxel and prednisone. The patients will receive up to 10 treatment
cycles of the combination therapy. Response to treatment will be assessed by measuring serum
levels of prostate specific antigen (PSA). Other efficacy measures will include radiological
assessment, progression-free survival, overall survival and quality of life.

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

- 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

- 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

- 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

- Uncontrolled or serious infection within the past four weeks

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Prostate Specific Antigen (PSA) response (incidence and duration)

Outcome Description:

70% of patients (n = 36) had a >50% reduction in PSA from baseline.

Outcome Time Frame:

Baseline and 6-8 weeks post enrolment

Safety Issue:


Principal Investigator

Gavin Marx, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Sydney Haematology and Oncology Clinics


United States: Food and Drug Administration

Study ID:




Start Date:

August 2005

Completion Date:

February 2008

Related Keywords:

  • Prostate Cancer
  • heparanase
  • angiogenesis
  • Prostatic Neoplasms