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Prostate CancerPhase 2NCT00268593

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

A Phase 2 study testing PI-88, docetaxel and prednisone in people with Prostate Cancer, run by Progen Pharmaceuticals at 8 sites in Australia.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, men only
Conditions the study is for
Prostate Cancer
What is being tested?
PI-88, docetaxel and prednisone
Could I receive a placebo?
No, everyone receives an active treatment
How many people
48 participants
Where
8 sitesAustralia
Study dates
Aug 2005to Feb 2008
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

Australia8 sites

  • Ashford Cancer Centre

    Ashford, South Australia, 5035

  • Sydney Haematology and Oncology Clinics

    Hornsby, New South Wales, 2077

  • St George Hospital

    Kogarah, New South Wales, 2217

  • Lismore Base Hospital

    Lismore, New South Wales, 2477

  • Port Macquarie Base Hospital

    Port Macquarie, New South Wales, 2444

  • Liverpool Cancer Therapy Centre

    Randwick, New South Wales, 2031

  • Royal North Shore Hospital

    St Leonards, New South Wales, 2065

  • Border Medical Oncology

    Wodonga, Victoria, 3690

Other trials in Australia

About this study

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

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.

Read the 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.

Conditions
Prostate Cancer
Being tested
PI-88, docetaxel, prednisone
Keywords
heparanase, angiogenesis
Medical subject headings
Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PI-88Drug

    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.

  • docetaxelDrug

    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.

  • prednisoneDrug

    5 mg twice a day orally

Study groups in NCT00268593
Study groupRoleWhat they receive
130 mg PI-88 + docetaxelExperimental130 mg PI-88 7 days/week + docetaxel 75 mg/m2
Receives: Drug: PI-88; Drug: docetaxel; Drug: prednisone
250 mg PI-88 + docetaxelExperimental250 mg PI-88 4 days/week + docetaxel 75 mg/m2
Receives: Drug: PI-88; Drug: docetaxel; Drug: prednisone

What is being measured

The primary outcome is the main question the study is designed to answer.

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

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

    Measured: Baseline and 6-8 weeks post enrolment

Secondary outcomes (7)

  1. 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.

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

  2. PSA progression-free survival

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

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

  3. Disease progression-free survival

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

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

  4. Overall survival

    Median survival was 61 weeks and 1-year survival was 71%.

    Measured: Survival data collected to 100 weeks

  5. Safety and tolerability

    Recruitment was stopped due to higher than expected febrile neutropenia rate (27%). Fifty-one SAEs were reported in 33 patients, of which 7 were related to PI-88 treatment: non-neutropenic sepsis, neutropenic sepsis, pulmonary embolism, febrile dyspnoea, haematuria (x2), left middle cerebral artery infarction.

    Grade 3 or 4 AEs reported in >5% of patients comprise dehydration, fatigue, diarrhoea, nausea and thrombocytopenia.

    Two patients died during the study, one due to a ruptured abdominal aortic aneurysm, and one due to metastatic prostate cancer.

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

  6. 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.

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

  7. Exploratory predictive value of biologic parameters C-reactive protein (CRP), vascular endothelial growth factor (VEGF), interleukin-6 (IL6), D-dimer

    Change in VEGF trended towards prediction of survival (p = 0.056); pre-treatment and post-treatment levels of CRP were predictive of survival (p = 0.026, and p = 0.005 respectively) but the change in CRP was not (p = 0.999). IL-6 pretreatment levels were not predictive (p = 0.5111) but post-treatment (p = 0.0008) and change (p = 0.0020) were.

    These data need to interpreted with caution due to the small patient numbers involved.

    Measured: Baseline and 6-8 weeks post enrolment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Dec 2005 (estimated)
  2. Study startAug 2005
  3. Primary completionFeb 2008
  4. Study completionFeb 2008

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
48 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00268593
Sponsor's protocol ID
PR88206
Other IDs
PROPIT, XRP6976J/6216
Status last verified
Jun 2011
First submitted
20 Dec 2005
Last updated
15 Jun 2011
Results posted
No

Publications

  • 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.

    PubMed 15470213

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing PI-88, docetaxel and prednisone in people with Prostate Cancer, run by Progen Pharmaceuticals at 8 sites in Australia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Jun 2011. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Prostate Specific Antigen (PSA) response (incidence and duration) (time frame: Baseline and 6-8 weeks post enrolment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00268593, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jun 2011.

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