hormone-resistant prostate cancer
Conditions
Interventions
Product Name: Zibotentan
Product Code: ZD4054
Pharmaceutical Form: Film-coated tablet
Current Sponsor code: ZD4054
Other descriptive name: Zibotentan
Concentration unit: mg milligram(s)
Concentration
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1.Provision of informed consent 2.Male, aged 18 years or older 3.Histological or cytological confirmation of adenocarcinoma of the prostate 4.Documented evidence of bone metastasis on bone scan. Patients must have disease involvement =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1.Radiotherapy to bone lesion or prostatic bed within 4 weeks of starting study treatment 2.Prior cytotoxic chemotherapy (such as paclitaxel, docetaxel and mitoxantrone) for the treatment of recurrent prostate cancer (prior estramustine therapy is allowed). Prior targeted cancer therapies, such as EGF, EGFR, VEGF and VEGFR, or immune cell therapy, are only permitted if the patient received them during participation in a previous clinical trial. 3.Systemic radionuclide therapy (ie, strontium chloride Sr89, 186Relabeled HEDP, or 153Sm-EDTMP pentasodium) within 12 weeks of starting study treatment 4.Use of potent CYP450 inducers (such as phenytoin, rifampicin, carbamazepine, phenobarbitone, St John’s Wort) within 2 weeks of starting study treatment. Dexamethasone is a known inducer of CYP2D6 and CYP3A4 but is acceptable for this study when used as part of the standard docetaxel regime 5.Use of systemic retinoids within 2 weeks of starting study treatment 6.Have received investigational drug in another clinical study of anti-cancer therapy, within 4 weeks of starting study treatment 7.Prior therapy with endothelin receptor antagonists or family history of hypersensitivity to endothelin antagonists 8.Acute or evolving spinal cord compression or neurological symptoms or signs consistent with this. If a patient has neurologic symptoms, an MRI must be performed that demonstrates no impending or actual spinal cord compression. Stable, previously treated patients are allowed 9.Symptomatic peripheral neuropathy of CTCAE grade 2 or higher 10.Known or suspected central nervous system metastases. 11.History of past or current epilepsy, epilepsy syndrome, or other seizure disorder 12.Stage II, III or IV cardiac failure (classified according to New York Heart Association (NYHA) classification) or myocardial infarction within 6 months prior to study entry 13.QT interval corrected for heart rate eg, by Bazett’s correction >470 msec 14.Previous history or presence of another malignancy within the preceding 5 years except treated squamous/basal cell carcinoma of the skin or melanoma that has been fully excised with no signs of residual disease or recurrence at the time of study enrolment. 15.In the opinion of the investigator, any evidence of severe or uncontrolled systemic disease, (eg, currently unstable or uncompensated respiratory, cardiac, hepatic or renal disease) or evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the patient to participate in the study 16.Absolute Neutrophil Count (ANC) 1.5 times the upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert’s syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of evidence of haemolysis or hepatic pathology), who will be allowed in consultation with their physician 18.Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2.5 times the ULN or 5 times the ULN in the presence of liver metastases 19.Creatinine clearance of <50 mL/minute, determined using the Cockcroft-Gault equation or by 24-hour creatinine clearance 20.Patients who have been previously randomised in this study cannot be rerandomised. Patients who fail to meet the inclusion/exclusion criteria may be recon
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the effect of ZD4054 in combination with docetaxel on overall survival compared with docetaxel; overall survival defined as time to death (from randomisation) from any cause;Secondary Objective: To assess/investigate the: *Effect of ZD4054 in combination with docetaxel on progression free survival compared with docetaxel. *Safety and tolerability profile of ZD4054 in combination with docetaxel compared with docetaxel *Effect of ZD4054 in combination with docetaxel on skeletal-related events compared with docetaxel. * Effect of ZD4054 in combination with docetaxel on time to prostate-specific antigen (PSA) progression compared to docetaxel *Effects of ZD4054 in combination with docetaxel on time to pain progression compared with docetaxel *Effects of ZD4054 in combination with docetaxel on pain response compared to docetaxel *Effect of ZD4054 in combination with docetaxel on Health-related Quality of Life (HRQoL) compared with docetaxel. *Effect of ZD4054 in combination with docetaxel on PSA response compared to docetaxel. ;Primary end point(s): overall survival defined as time to death (from randomisation) from any cause | — |
Countries
Finland, France, Germany, Hungary, Italy, Netherlands, Portugal, Spain, Sweden, United Kingdom
Outcome results
None listed