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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT00268593




Registration number
NCT00268593
Ethics application status
Date submitted
20/12/2005
Date registered
22/12/2005
Date last updated
15/06/2011

Titles & IDs
Public title
Pilot Efficacy Study of PI-88 With Docetaxel to Treat Prostate Cancer
Scientific title
A Randomised Phase II Study of Two Dose Schedules of PI-88 in Combination With Docetaxel in Patients With Androgen-independent Prostate Cancer
Secondary ID [1] 0 0
PROPIT
Secondary ID [2] 0 0
PR88206
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prostate Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - PI-88
Treatment: Drugs - docetaxel
Treatment: Drugs - prednisone

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

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


Treatment: Drugs: PI-88
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.

Treatment: Drugs: docetaxel
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.

Treatment: Drugs: prednisone
5 mg twice a day orally
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Prostate Specific Antigen (PSA) response (incidence and duration)
Timepoint [1] 0 0
Baseline and 6-8 weeks post enrolment
Secondary outcome [1] 0 0
Radiologic response rate in patients with measurable disease
Timepoint [1] 0 0
Recruitment was stopped early due to elevated rates of febrile neutropenia. This end point was not reported.
Secondary outcome [2] 0 0
PSA progression-free survival
Timepoint [2] 0 0
Recruitment was stopped early due to elevated rates of febrile neutropenia. This end point was not reported.
Secondary outcome [3] 0 0
Disease progression-free survival
Timepoint [3] 0 0
Recruitment was stopped early due to elevated rates of febrile neutropenia. This end point was not reported.
Secondary outcome [4] 0 0
Overall survival
Timepoint [4] 0 0
Survival data collected to 100 weeks
Secondary outcome [5] 0 0
Safety and tolerability
Timepoint [5] 0 0
Recruitment was stopped early due to elevated rates of febrile neutropenia. Safety data collected throughout duration.
Secondary outcome [6] 0 0
Quality of life Functional Assessment of Cancer Therapy - Prostate questionnaire (FACT-P)
Timepoint [6] 0 0
Recruitment was stopped early due to elevated rates of febrile neutropenia. This end point was not reported.
Secondary outcome [7] 0 0
Exploratory predictive value of biologic parameters C-reactive protein (CRP), vascular endothelial growth factor (VEGF), interleukin-6 (IL6), D-dimer
Timepoint [7] 0 0
Baseline and 6-8 weeks post enrolment

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Males
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/08/2005
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/02/2008
Sample size
Target
Accrual to date
Final
48
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 0 0
Sydney Haematology and Oncology Clinics - Hornsby
Recruitment hospital [2] 0 0
St George Hospital - Kogarah
Recruitment hospital [3] 0 0
Lismore Base Hospital - Lismore
Recruitment hospital [4] 0 0
Port Macquarie Base Hospital - Port Macquarie
Recruitment hospital [5] 0 0
Liverpool Cancer Therapy Centre - Randwick
Recruitment hospital [6] 0 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [7] 0 0
Ashford Cancer Centre - Ashford
Recruitment hospital [8] 0 0
Border Medical Oncology - Wodonga
Recruitment postcode(s) [1] 0 0
2077 - Hornsby
Recruitment postcode(s) [2] 0 0
2217 - Kogarah
Recruitment postcode(s) [3] 0 0
2477 - Lismore
Recruitment postcode(s) [4] 0 0
2444 - Port Macquarie
Recruitment postcode(s) [5] 0 0
2031 - Randwick
Recruitment postcode(s) [6] 0 0
2065 - St Leonards
Recruitment postcode(s) [7] 0 0
5035 - Ashford
Recruitment postcode(s) [8] 0 0
3690 - Wodonga

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Progen Pharmaceuticals
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Northern Sydney and Central Coast Area Health Service
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/Industry
Name [2] 0 0
Aventis Pharmaceuticals
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT00268593
Trial related presentations / 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.
Public notes

Contacts
Principal investigator
Name 0 0
Gavin Marx, MD
Address 0 0
Sydney Haematology and Oncology Clinics
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries