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

NCT00268593 | Completed Phase 2

• 3 other identifiers: PR88206PROPITXRP6976J/6216
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 8

Brief 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.

Conditions

Prostate Cancer

Keywords

heparanase; angiogenesis

Outcome Measures

Primary Outcomes (1)

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

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

  Baseline and 6-8 weeks post enrolment

Secondary Outcomes (7)

• Radiologic response rate in patients with measurable disease

  Recruitment was stopped early due to elevated rates of febrile neutropenia. This end point was not reported.

• PSA progression-free survival

  Recruitment was stopped early due to elevated rates of febrile neutropenia. This end point was not reported.

• Disease progression-free survival

  Recruitment was stopped early due to elevated rates of febrile neutropenia. This end point was not reported.

• Overall survival

  Survival data collected to 100 weeks

• Safety and tolerability

  Recruitment was stopped early due to elevated rates of febrile neutropenia. Safety data collected throughout duration.

Study Arms (2)

130 mg PI-88 + docetaxel

EXPERIMENTAL

130 mg PI-88 7 days/week + docetaxel 75 mg/m2

Drug: PI-88; Drug: docetaxel; Drug: prednisone

250 mg PI-88 + docetaxel

EXPERIMENTAL

250 mg PI-88 4 days/week + docetaxel 75 mg/m2

Drug: PI-88; Drug: docetaxel; Drug: prednisone

Interventions

PI-88 DRUG

Subcutaneous injection administered 7 days/week for 130 mg PI-88 and 4 days/week for 250 mg PI-88; patients to be treated until progression or withdrawal from study.

130 mg PI-88 + docetaxel; 250 mg PI-88 + docetaxel

docetaxel DRUG

Subcutaneous injection administered 7 days/week for 130 mg PI-88 and 4 days/week for 250 mg PI-88; patients to be treated until progression or withdrawal from study.

130 mg PI-88 + docetaxel; 250 mg PI-88 + docetaxel

prednisone DRUG

5 mg twice a day orally

130 mg PI-88 + docetaxel; 250 mg PI-88 + docetaxel

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Progen Pharmaceuticals: lead
• Northern Sydney and Central Coast Area Health Service: collaborator
• Aventis Pharmaceuticals: collaborator

Study Sites (8)

Sydney Haematology and Oncology Clinics

Hornsby, New South Wales, 2077, Australia

Location

St George Hospital

Kogarah, New South Wales, 2217, Australia

Location

Lismore Base Hospital

Lismore, New South Wales, 2477, Australia

Location

Port Macquarie Base Hospital

Port Macquarie, New South Wales, 2444, Australia

Location

Liverpool Cancer Therapy Centre

Randwick, New South Wales, 2031, Australia

Location

Royal North Shore Hospital

St Leonards, New South Wales, 2065, Australia

Location

Ashford Cancer Centre

Ashford, South Australia, 5035, Australia

Location

Border Medical Oncology

Wodonga, Victoria, 3690, Australia

Location

Related Publications (1)

• Tannock IF, de Wit R, Berry WR, Horti J, Pluzanska A, Chi KN, Oudard S, Theodore C, James ND, Turesson I, Rosenthal MA, Eisenberger MA; TAX 327 Investigators. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med. 2004 Oct 7;351(15):1502-12. doi: 10.1056/NEJMoa040720.

  PMID: 15470213 BACKGROUND

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

phosphomannopentaose sulfate; Docetaxel; Prednisone

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Gavin Marx, MD

  Sydney Haematology and Oncology Clinics

  STUDY CHAIR

• Nick Pavlakis, MD

  Royal North Shore Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: December 20, 2005
• First Posted: December 22, 2005
• Study Start: August 1, 2005
• Primary Completion: February 1, 2008
• Study Completion: February 1, 2008
• Last Updated: June 15, 2011

Record last verified: 2011-06

Locations

AU (8)