A phase II, double-blind, placebo-controleed, randomised study to assess the efficacy and safety of docetaxel (Taxotere)/ prednisolone/ ZD6474 vs. docetaxel/ prednisolone/ placebo in patients with hormone refractory prostate cancer (HRPC)
- Conditions
- Hormone refractory prostate cancer (HRPC)
- Registration Number
- EUCTR2005-003593-16-SE
- Lead Sponsor
- AstraZeneca AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Male
- Target Recruitment
- 85
1. Provision of informed consent
2. Male patients aged 18 years and over
3. Metastatic hormone refractory prostate cancer defined as those patients with evidence of progression of disease in spite of castrate levels of testosterone indicated by rising levels of PSA.
4. Patients with a serum testosterone < or = 50ng/dL (1.73nmol/L)
5. No previous chemotherapy although those patients that have received estramustine can enter the study provided the estramustine was stopped 3 weeks before dosing of study drug.
6. Performance status 0-2 and life expectancy > 12 weeks.
7. Screening PSA values > 20 ng/ml. This must be confirmed by two separate measurements at least 2 weeks apart
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
1. Treatment within 4 weeks before randomisation and/or whilst on study, treatment with the following: a non-approved or experimental drug; a drug with similar mechanism of action to ZD6474
2. Concurrent treatment with other anticancer agents, other than docetaxel and prednisolone as defined in the protocol.
3. Severe obstructive urinary symptoms or macroscopic haematuria
4. Major surgery within 4 weeks of randomisation or incompletely healed surgical incision
5. History of hypersensitivity to active or inactive excipients of ZD6474, docetaxel, prednisolone or placebo.
6. Current or prior malignancy within previous 3 years (other than prostate cancer or adequately treated basal cell or squamous cell carcinoma of the skin).
7. Any of the following laboratory values: total bilirubin > ULRR; ALT or AST > 2.5 x ULRR; serum creatinine > 1.5 x ULRR and creatinine clearance < or = 50mL/minute (calculated by Cockcroft-Gault formula)
8. Any of the following laboratory values: platelets < 100 x10e9/l; ANC < 1.5 x 10e9/l
9. Potassium < 4.0mmol despite supplementation; serum calcium (or ionised or adjusted for albumin), or magnesium out of normal range despite supplementation
10. Significant cardiovascular event (e.g. myocardial infarction, superior vena cava syndrome, New York Heart Association classification of heart disease > or =2) within 3 months before entry, or presence of cardiac disease that, in the opinion of the investigator, increases the risk of ventricular arrhythmia
11. History of arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia, symptomatic or uncontrolled atrial fibrillation) which is symptomatic or requires treatment (CTCAE grade 3) or asymptomatic sustained ventricular tachycardia. Atrial fibrillation, controlled on medication, is not excluded
12. Congenital long QT syndrome or 1st degree relative with unexplained sudden death under 40 years of age
13. QT prolongation with other medication that requires discontinuation of that medication
14. Presence of left bundle branch block
15. QTc with Bazett’s correction unmeasurable or > or = 480msec or greater on screening ECG (Note: if patient has QTc interval > or = 480msec on screening ECG, the screen ECG may be repeated twice [at least 24 hours apart]. The average QTc from the 3 screening ECGs must be <480msec for the patient to be eligible for the study)
16. Any concomitant medications that may cause QTc prolongation or induce Torsades de Pointes (as defined in the protocol)
17. Any severe concomitant condition which, in the Investigator’s opinion, makes it undesirable for the patient to participate in the study or which would jeopardize compliance with the study protocol. e.g. uncontrolled cardiac disease
18. Currently receiving the following drugs that are potent inducers of CYP P450 3A4 - phenytoin, rifampicin, carbamezapine, phenobarbitone and St Johns Wort
19. Hypertension not controlled by medical therapy (systolic blood pressure >160 mmHg or diastolic blood pressure >110 mmHg)
20. Involvement in the planning and conduct of the study (applies to both AstraZeneca staff or staff at the study site)
21. Previous enrolment or randomisation of treatment in the present study.
22. Any unresolved toxicity > Common Toxicity Criteria (CTC) grade 2 from previous anticancer therapy.
23. Brain metastases or spinal cord compression, unless treated at least 4 weeks before entry, and stable wit
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To assess the efficacy of ZD6474 in combination with docetaxel/prednisolone in the treatment of HRPC by the rate of prostate specific antigen (PSA) fall.;Secondary Objective: To assess the safety and tolerability of ZD6474 in combination with docetaxel and prednisolone in the treatment of HRPC by review of adverse events and laboratory parameters.<br><br>To assess the efficacy of ZD6474/docetaxel/prednisolone treatment results in a lower relative risk of progression (after 8 months minimum follow-up) against docetaxel/prednisolone alone using the progression event count methodology.<br>;Primary end point(s): The primary outcome variable is defined as a PSA response. A PSA response is defined as a 50% reduction from baseline at any assessment.<br>
- Secondary Outcome Measures
Name Time Method