E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic Castrate Refractory Prostate Cancer |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
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 |
The STAMPEDE and GETUG-12 trials are evaluating the early use of docetaxel in high risk prostate cancer patients. Currently the standard of care in first line metastatic CRPC (mCRPC) is docetaxel, and as most of the patients enrolled in STAMPEDE will ultimately relapse with mCRPC and a majority of those relapsing would be fit for further chemotherapy, it is debatable whether further chemotherapy should be regarded as first line mCRPC chemotherapy or second line. The TROPIC trial, which compared cabazitaxel with mitoxantrone in patients previously treated with docetaxel, has shown a statistically significant survival advantage with cabazitaxel. In light of the positive results from the TROPIC trial, there is an opportunity to investigate the role of cabazitaxel as a second line treatment in patients with mCRPC, previously treated with docetaxel within STAMPEDE. Both cabazitaxel and abiraterone have recently been licensed for treatment of mCRPC in the second line setting. It is al |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Diagnosis of histologically proven prostate adenocarcinoma, that is castrate refractory 2. Previously treated with up to 6 cycles of Docetaxel at the same time (defined as commencing within 3 months) as instigation of primary hormone therapy. 3. Confirmed biochemical, radiological or clinical progression. 4. Metastatic disease 5. Aged 18 or over 6. WHO performance status grade 0 to 2 7. Adequate organ function as evidenced by: --ANC >1.5 x109/L --WBC >3.0 x109/L --Haemoglobin >10g/dL --Platelet count >100,000/mm3 --Total bilirubin <1.5 xULN --AST/ALT <1.5 xULN --GFR >30ml/min (calculated by EDTA clearance, 24h urine collection, or Cockcroft-Gault) --Available for long-term follow up --Patient’s written informed consent |
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E.4 | Principal exclusion criteria |
1. Prior systemic therapy with other chemotherapy drugs 2. Metastatic brain disease or leptomeningeal disease 3. Previous extensive palliative radiotherapy to bone marrow, e.g. hemibody radiotherapy 4. Active grade ≥2 peripheral neuropathy (NCI CTC v 4) 5. Active infection requiring systemic antibiotic or anti-fungal medication 6. Patients with reproductive potential not implementing accepted and effective method of contraception |
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E.5 End points |
E.5.1 | Primary end point(s) |
Clinical Progression-free survival (CPFS). Clinical progression is defined as the earliest of the: • Date of occurrence of pain progression • Date of occurrence of a cancer-related skeletal-related event • Date of death from any cause |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Estimates of time to progression and time to death will be calculated using the Kaplan-Meier method. Median and 6-month ‘survival’ estimates will be presented with confidence intervals. A hazard ratio of the treatment effect will be estimated and presented with 95% confidence intervals. Primary analysis is planned when all patients have a minimum of 12 months follow-up following registration. The final study analysis will take place when all patients have completed 24 months follow up. |
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E.5.2 | Secondary end point(s) |
To determine: • Toxicity (National Cancer Institute Common Toxicity Criteria version 4) • Skeletal-related-event-free survival • Pain progression-free survival • PSA-progression free survival • Overall survival • Quality of life |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The proportion of patients experiencing grade 3 and grade 4 toxicities on each arm will be reported as a proportion of i) all patients randomised in the trial and ii) all patients receiving at least one dose of treatment in the trial. Changes in pain score and QoL will be assessed using longitudinal methods of analysis and will account for informative dropout, including dropout for death. The final study analysis will take place when all patients have completed 24 months follow up. |
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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 | Yes |
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 | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | No |
E.8.1.5 | Parallel group | No |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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.8.4.1 | Number of sites anticipated in Member State concerned | 10 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
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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For the purpose of complying with UK Clinical Regulations introduced on May 2004, the trial will be considered ‘closed’ when the last patient has completed protocol treatment plus 30 days. This will allow sufficient time for the completion of protocol procedures, data collection and data input. For the purposes of main REC approval, the trial end date is deemed to be the date of the latest data capture following 2 years of long-term follow up |
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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 | 5 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 5 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 5 |