A Randomised Phase II Study of Two Dose Schedules of PI-88 in Combination With Docetaxel in Patients With Androgen-independent Prostate Cancer
Overview
- Phase
- Phase 2
- Intervention
- PI-88
- Conditions
- Prostate Cancer
- Sponsor
- Progen Pharmaceuticals
- Enrollment
- 48
- Locations
- 8
- Primary Endpoint
- Prostate Specific Antigen (PSA) response (incidence and duration)
- Status
- Completed
- Last Updated
- 14 years ago
Overview
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.
Detailed Description
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.
Investigators
Eligibility 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 \<
- •Neutrophil count \> 1.5 x 109/L (1,500/mm3)
- •Haemoglobin \> 10 g/dL
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
Arms & Interventions
130 mg PI-88 + docetaxel
130 mg PI-88 7 days/week + docetaxel 75 mg/m2
Intervention: PI-88
130 mg PI-88 + docetaxel
130 mg PI-88 7 days/week + docetaxel 75 mg/m2
Intervention: docetaxel
130 mg PI-88 + docetaxel
130 mg PI-88 7 days/week + docetaxel 75 mg/m2
Intervention: prednisone
250 mg PI-88 + docetaxel
250 mg PI-88 4 days/week + docetaxel 75 mg/m2
Intervention: PI-88
250 mg PI-88 + docetaxel
250 mg PI-88 4 days/week + docetaxel 75 mg/m2
Intervention: docetaxel
250 mg PI-88 + docetaxel
250 mg PI-88 4 days/week + docetaxel 75 mg/m2
Intervention: prednisone
Outcomes
Primary Outcomes
Prostate Specific Antigen (PSA) response (incidence and duration)
Time Frame: Baseline and 6-8 weeks post enrolment
70% of patients (n = 36) had a \>50% reduction in PSA from baseline.
Secondary Outcomes
- 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.)
- Quality of life Functional Assessment of Cancer Therapy - Prostate questionnaire (FACT-P)(Recruitment was stopped early due to elevated rates of febrile neutropenia. This end point was not reported.)
- Exploratory predictive value of biologic parameters C-reactive protein (CRP), vascular endothelial growth factor (VEGF), interleukin-6 (IL6), D-dimer(Baseline and 6-8 weeks post enrolment)