E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
metastatic Castration Resistant Prostate cancer |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10060862 |
E.1.2 | Term | Prostate cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 demonstrate the superiority of cabazitaxel plus prednisone at 25 mg/m² (Arm A) or 20 mg/m² (Arm B) versus docetaxel plus prednisone (Arm C) in term of overall survival (OS) in patients with metastatic castration resistant prostate cancer (MCRPC) and not previously treated with chemotherapy |
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E.2.2 | Secondary objectives of the trial |
* Evaluate safety in the 3 treatment arms * Compare efficacy of cabazitaxel at 20 mg/m² and 25 mg/m² to docetaxel for: - Progression Free Survival (PFS) defined as the first occurrence of any of the following events: tumor progression per Response Evaluation Criteria In Solid Tumors (RECIST 1.1), PSA progression, pain progression or death due to any cause - Tumor progression free survival defined as the first occurrence of any of the following events: tumor progression per Response Evaluation Criteria In Solid Tumors (RECIST 1.1) or death due to any cause - Tumor response in patients with measurable disease (RECIST 1.1). - PSA response - PSA-Progression free survival (PSA-PFS). - Pain response in patients with stable pain at baseline. - Pain progression free survival - Time to occurrence of any skeletal related events (SRE). * To compare Health-Related Quality of Life (HRQL) * To assess the pharmacokinetic of cabazitaxel |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Histologically- or cytologically-confirmed prostate adenocarcinoma. 2.Metastatic disease. 3.Progressive disease while receiving hormonal therapy or after surgical castration documented 4.Effective castration (serum testosterone levels ≤ 0.50 ng/mL) by orchiectomy and/or LHRH agonists or antagonist with or without anti-androgens. |
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E.4 | Principal exclusion criteria |
1.Prior chemotherapy for prostate cancer, except estramustine and except adjuvant/neoadjuvant treatment completed > 3 years ago. Prior treatment with sipuleucel-T immunotherapy is allowed at the condition patient did not received prior chemotherapy. 2.Less than 28 days elapsed from prior treatment with estramustine, radiotherapy or surgery to the time of randomization. Patients may be on biphosphonates prior to study entry. 3.Prior isotope therapy, whole pelvic radiotherapy, or radiotherapy to > 30% of bone marrow. 4.Adverse events (excluding alopecia and those listed in the specific exclusion criteria) from any prior anticancer therapy of grade >1(National Cancer Institute Common Terminology Criteria [NCI CTCAE] v4.03) at the time of randomization. 5.Less than 18 years. 6.Eastern Cooperative Oncology Group (ECOG) performance status > 2. 7.History of brain metastases, uncontrolled spinal cord compression, or carcinomatous meningitis or new evidence of brain or leptomeningeal disease. 8.Prior malignancy. Adequately treated basal cell or squamous cell skin or superficial (pTis, pTa, and pT1) bladder cancer are allowed, as well as any other cancer for which chemotherapy has been completed ≥ 5 years ago and from which the patient has been disease-free for ≥ 5 years. 9.Participation in another clinical trial and any concurrent treatment with any investigational drug within 30 days prior to randomization. 10.Any of the following within 6 months prior to study enrollment: myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, NYHA class III or IV congestive heart failure, stroke or transient ischemic attack. 11.Any of the following within 3 months prior to randomization: treatment resistant peptic ulcer disease, erosive esophagitis or gastritis, infectious or inflammatory bowel disease, diverticulitis, pulmonary embolism, or other uncontrolled thromboembolic event. 12.Acquired immunodeficiency syndrome (AIDS-related illnesses) or known HIV disease requiring antiretroviral treatment. 13.Any severe acute or chronic medical condition which could impair the ability of the patient to participate to the study or interfere with interpretation of study results or patients unable to comply with the study procedures. 14.Absence of signed and dated Institutional Review Board (IRB)-approved patient informed consent form prior to enrollment into the study. 15.Patients with reproductive potential who do not agree to use accepted and effective method of contraception during the study treatment period. The definition of “effective method of contraception” will be based on the investigator’s judgment. For patients enrolled in the United Kingdom, their partner (unless surgically sterile, post menopausal or for another reason have no chance of becoming pregnant) should use an effective means of contraception described hereafter: oral contraceptives or intra uterine device. Related to chemotherapy 16.History of hypersensitivity to docetaxel, or polysorbate 80. 17.Inadequate organ and bone marrow function as evidenced by: a.Hemoglobin <10.0 g/dL b.Absolute neutrophil count <1.5 x 109/L c.Platelet count < 100 x 109/L d.AST/SGOT and/or ALT/SGPT > 1.5 x ULN; e.Total bilirubin > 1.0 x ULN f.Serum Creatinine > 1.5 x ULN. If creatinine 1.0 - 1.5 x ULN, creatinine clearance will be calculated either according to Cockcroft-Gault formula for patients younger than 65 years or, according to aMDRD formula for patients ≥ 65 years) Creatinine clearance < 60 mL/min will exclude the patient (see Appendix A for calculation formula) 18.Contraindications to the use of corticosteroid treatment. 19.Symptomatic peripheral neuropathy grade > 2 (National Cancer Institute Common Terminology Criteria [NCI CTCAE] v.4.03). |
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E.5 End points |
E.5.1 | Primary end point(s) |
OS defined as the time interval from the date of randomization to the date of death due to 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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
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) | 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 | 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) | 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.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 54 |
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 | Yes |
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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The maximum study duration and the final study cut-off date for survival will be the date when approximately 774 deaths have occurred or approximately 516 deaths if one of the cabazitaxel arm is prematurely stopped. |
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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 | 7 |
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 | 7 |