E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with Hormone-resistant Prostate Cancer and Bone Metastasis who are Pain Free or Mildly Symptomatic |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10036911 |
E.1.2 | Term | Prostate cancer recurrent |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine the effect of ZD4054 on overall survival, defined as time to death (from randomisation) from any cause, compared to placebo |
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E.2.2 | Secondary objectives of the trial |
1. To assess the effect of ZD4054 on progression free survival, defined as time from randomisation into the study until clinical progression of disease, compared to placebo 2. To investigate the tolerability and safety profile of ZD4054 compared to placebo 3. To assess the effect of ZD4054 on time to use of opiates compared to placebo 4. To assess the effect of ZD4054 on the incidence of skeletal related events compared to placebo 5. To investigate the effects of ZD4054 on bone metastases formation compared to placebo 6. To assess the effects of ZD4054 on Health Related Quality of Life (HRQOL) compared to placebo 7. To investigate the effect of ZD4054 on time to prostate-specific antigen (PSA) progression compared to placebo 8. To assess the effects of ZD4054 on time to pain progression compared to placebo 9. To investigate the effects of ZD4054 on time to initiation of chemotherapy compared to placebo 1o. ...... |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal 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 radionuclide bone scan. Patients must have disease involvement <75% of the spine, pelvis and ribs in the anteroposterior (AP) or posteroanterior (PA) view. Patients with ≤3 lesions seen on bone scan will require a CT scan, MRI or x-ray to confirm 5. Biochemical progression of prostate cancer, documented while the patient is castrate: − Biochemical progression is defined as at least 2 stepwise increases in PSA over a period of ≥1 month (values do not need to be consecutive but 2 values that have increased since the previous highest value are required) with at least 14 days between each measurement irrespective of assay or laboratory − Historical values may be used − The last PSA must be an increase of ≥50 % of the first PSA value of the 3 values or an absolute increase of ≥10 ng/mL over the initial PSA − The final PSA value must be ≥1.2 ng/mL in patients who have had a radical prostatectomy and ≥5 ng/mL in all other patients 6. Asymptomatic or mild pain from prostate cancer, defined as a score of ≤2 in the worst pain item of the BPI 7. Surgically castrated or continuously medically castrated with serum testosterone ≤2.4 nmol/L (70 ng/dL) 8. World Health Organisation (WHO) performance status 0 - 1 9. Life expectancy of 6 months or more. |
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E.4 | Principal exclusion criteria |
1. Radiotherapy to bone lesion or prostatic bed within 4 weeks of starting study treatment 2. Current use (from the time that written informed consent is given) of any opiates, with the exception of opiates taken PRN for pain not directly related to prostate cancer 3. Prior cytotoxic chemotherapy (such as paclitaxel, docetaxel and mitoxantrone) for the treatment of recurrent prostate cancer (prior estramustine therapy is allowed), as well as other targeted cancer therapies (such as EGF, EGFR, VEGF and VEGFR) 4. Systemic radionuclide therapy (ie, strontium chloride Sr89, 186Relabeled HEDP, or 153Sm-EDTMP pentasodium) within 12 weeks of starting study treatment 5. Use of potent CYP450 inducers (such as phenytoin, rifampicin, carbamazepine, phenobarbitone and St Johns Wort) within 2 weeks of starting study treatment. Dexamethasone will be allowed if the investigator feels it is necessary but is encouraged to use a different form of steroid treatment wherever possible 6. Use of systemic retinoids within 2 weeks of starting study treatment 7. Have received investigational drug in another clinical study of anticancer therapy, within 4 weeks of starting study treatment 8. Prior therapy with endothelin receptor antagonists or family history of hypersensitivity to endothelin antagonists 9. Neurological symptoms or signs consistent with acute or evolving spinal cord compression. 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 10. Symptomatic peripheral neuropathy of CTCAE grade 2 or higher 11. Known or suspected central nervous system metastases 12. History of past or current epilepsy, epilepsy syndrome, or other seizure disorder 13. 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 14. QT interval corrected for heart rate eg, by Bazetts correction >470 msec 15. Previous history or presence of another malignancy, other than prostate cancer or treated squamous/basal cell carcinoma of the skin, within the last 5 years 16. 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 17. Hemoglobin (Hb) <9 g/dL. Concomitant use of erythropoietin or blood transfusions is allowed 18. Serum bilirubin >1.5 times the upper limit of normal (ULN). This will not apply to patients with Gilberts 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 19. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2.5 times the ULN or 5 times the ULN in the presence of liver metastasis 20. Creatinine clearance of <50 mL/minute, determined using the Cockcroft-Gault equation or by 24-hour creatinine clearance 21. ...... |
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E.5 End points |
E.5.1 | Primary end point(s) |
Overall survival defined as: Time to death (from randomisation) from any cause |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |