E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Prostate Cancer at High Risk of Relapse After Radical Prostatectomy |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10060862 |
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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 |
The primary objective of the study is to compare progression-free survival (PSA progression after systemic treatment, radiologically or histologically documented progression after systemic treatment or death from any cause, whichever occurs first), using a 2x2 factorial design among treatment groups as follows: • Immediate treatment following prostatectomy [Treatment Arms: I(CHT), I(HT)] versus deferred treatment at the time of relapse [Treatment Arms: D(CHT), D(HT)] • TAXOTERE® q3w plus ELIGARD® (leuprolide acetate) [Treatment Arms: I(CHT), D(CHT)] versus ELIGARD® alone [Treatment Arms: I(HT), D(HT)]
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are: • To compare the 5-year overall, cancer-specific and metastasis-free survival (metastasis-free survival based on time to clinical evidence of metastasis evidenced by physical exam or radiologically on bone scan or CT scan) after systemic treatment between the groups defined as follows:
- Immediate treatment following prostatectomy [Treatment Arms: I(CHT), I(HT)] versus deferred treatment [Treatment Arms: D(CHT), D(HT)] - TAXOTERE® q3w plus ELIGARD® [Treatment Arms: I(CHT), D(CHT)] versus ELIGARD® alone [Treatment Arms: I (HT), D (HT)] • To compare the safety and tolerability between TAXOTERE® in combination with ELIGARD® and ELIGARD® alone. • To evaluate quality of life as measured by the FACT-P questionnaire.
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Patients meeting all of the following criteria will be considered for enrollment into the study: 1- Pathologically confirmed adenocarcinoma of the prostate based on central pathology review. All other variants are excluded 2- Randomization should occur less than 90 days after prostatectomy AND lymphadenectomy. (Instructions for Radical Prostatectomy, Appendix H) 3- A predicted probability of 5-year freedom from progression ≤ 60%, as determined by the postoperative nomogram developed by M. Kattan. This probability will be assessed using data from the prostatectomy specimen central review (Johns Hopkins, USA and Karolinska Institute, Sweden). 4- Bone-scan without evidence of metastasis (within 6 months of randomization) 5- Chest x-ray without evidence of metastasis (within 6 months of randomization) 6- Abdominal CT Scan without evidence of metastasis (within 6 months of randomization) 7- Age ≥18 years 8- ECOG performance status ≤ 1 (Appendix A) 9- Hematology evaluation within 2 weeks prior to randomization: a. Neutrophils ≥ 2,000/mm3 b. Hemoglobin ≥ 10 g/dL c. Platelets ≥ 100,000/mm3 10- Hepatic and renal function evaluation within 2 weeks prior to randomization: a. Serum creatinine ≤1.5 × UNL for the institution. If serum creatinine is > 1.5 × UNL, calculated creatinine clearance (should be ≥ 60ml/minute). b. Total serum bilirubin ≤ UNL for the institution. Patients with Gilbert’s syndrome may be eligible if indirect serum bilirubin levels at the time of randomization and, at least 6 month prior to randomization, confirm this condition (i.e. elevated indirect serum bilirubin). c. SGOT and/or SGPT ≤ 1.5 × institutional UNL if alkaline phosphatase is ≤ UNL OR d. alkaline phosphatase < 5 × UNL if SGOT and SGPT are ≤ UNL 11- PSA evaluation within 6 months prior to prostatectomy. However, a 90-day timeframe is recommended 12- Undetectable PSA (defined as ≤ 0.1ng/mL using a standard assay) at least 30 days after radical prostatectomy. Note that randomization should occur within 90 days after radical prostatectomy (see inclusion criterion 2). 13- Serum testosterone ≥ 150 ng/dL within 6 months prior to randomization. 14- Life expectancy ≥ 5 years 15- Signed, written informed consent prior to randomization. 16- Patients must be accessible for treatment and follow-up. Patients randomized in this trial must be treated and followed at the participating center.
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E.4 | Principal exclusion criteria |
Patients presenting with any of the following will not be included in the study: 1- Prior systemic treatment for prostate cancer with hormonal therapy, chemotherapy, or any other anticancer therapy. 2- Prior radiation therapy. 3- Patients who received, are receiving, or scheduled to receive post-operative radiotherapy. 4- Patients taking alternative therapies for cancer must stop taking these therapies prior to randomization. Alternative therapies are not allowed during the treatment or follow-up portions of the study. This includes (but is not limited to) alternative therapies such as: a. PC-SPES (all types) b. 5-alpha reductase inhibitors 5- Bisphosphonates are to be stopped prior to randomization and are not allowed during the study. 6- Chronic treatment with corticosteroids unless initiated > 6 months prior to study entry and at low dose (≤ 20 mg methylprednisolone per day or equivalent). 7- History of a malignancy other than prostate cancer. Exceptions to these criteria include: a. patients with adequately treated non-melanoma skin cancers, and b. patients with a history of another malignancy that was curatively treated (including patients with superficial bladder cancer) and who have not had evidence of disease for a minimum of 5 years. 8- Peripheral neuropathy ≥ Grade 2. 9- ECG with significant abnormalities (as determined by the investigator) within 90 days prior to randomization. 10- Psychological, familial, sociological, or geographical conditions, which do not permit treatment and/or medical follow-up, required to comply with the study protocol. 11- Patients who are medically unstable, including but not limited to active infection, acute hepatitis, gastrointestinal bleeding, uncontrolled cardiac arrhythmias, interstitial lung disease, inflammatory bowel disease, uncontrolled angina, uncontrolled hypercalcemia, uncompensated congestive heart failure, uncontrolled diabetes, dementia, seizures, superior vena cava syndrome. 12- Patients with history of hypersensitivity to polysorbate 80. 13- Patients with a known history of viral hepatitis (B, C)
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary analysis variable is progression-free survival (PFS) after protocol-defined systemic therapy. PFS is defined as the interval from the date of surgery to the date of PSA progression after systemic treatment, date of radiologically or histologically documented progression after systemic treatment or date of death from any cause, whichever occurs first.
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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 | Information not present in EudraCT |
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) | 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 | Yes |
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.8.3 |
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 | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 6 |