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.1.3 | 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 non inferiority in term of overall survival (OS) of cabazitaxel 20 mg/m² (Arm A) versus cabazitaxel 25 mg/m² (Arm B) in combination with prednisone in patients with metastatic castration resistant prostate (MCRPC) previously treated with a docetaxel-containing regimen |
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E.2.2 | Secondary objectives of the trial |
* To evaluate safety in the 2 treatment arms and to assess if cabazitaxel 20 mg/m² is better tolerated than cabazitaxel 25 mg/m². * To compare efficacy of cabazitaxel at 20 mg/m² and 25 mg/m² 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), PSA progression, pain progression or death due to any cause - PSA-Progression - Pain progression - Tumor response in patients with measurable disease (RECIST 1.1). - PSA response - Pain response in patients with stable pain at baseline. * To compare Health-related Quality of Life (HRQL) * To assess the pharmacokinetics of cabazitaxel
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Diagnosis of histologically or cytologically proven prostate adenocarcinoma, that is resistant to hormone therapy and previously treated with a docetaxel-containing regimen. Patient must have documented progression of disease during or within 6 months after prior hormone therapy and disease progression during or after docetaxel-containing therapy. 2.Patient must have either measurable or non-measurable disease. 3.Received prior castration by orchiectomy and/or Luteinizing Hormone-Releasing Hormone (LH-RH) agonist with or without antiandrogen, antiandrogen withdrawal, monotherapy with estramustine, or other hormonal agents. 4.Life expectancy > 6 months 5.Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 – 2 (ie, patient must be ambulatory, capable of all self-care, and up and about more than 50% of waking hours) 6.Age ≥18 years
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E.4 | Principal exclusion criteria |
1.Previous treatment with mitoxantrone or cabazitaxel 2.Prior isotope therapy or radiotherapy to ≥30% of bone marrow. In case of prior isotope therapy 12 weeks must have elapsed prior to first study drug administration. 3.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. 4.Prior surgery, radiation, chemotherapy, or other anti-cancer therapy within 4 weeks prior to enrollment in the study 5.Prior malignancy. Adequately treated basal cell or squamous cell skin or in situ 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 6.Participation in another clinical trial and any concurrent treatment with any investigational drug within 30 days prior to randomization. 7.Known brain or leptomeningeal involvement 8.Other concurrent serious illness or medical conditions 9.Uncontrolled cardiac arrhythmias, angina pectoris, and/or hypertension. History of congestive heart failure or myocardial infarction within last 6 months is also not allowed. 10.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. 11.Absence of signed and dated Institutional Review Board (IRB)-approved patient informed consent form prior to enrollment into the study. 12.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. Patients' Partners of childbearing potential (unless surgically sterile, post menopausal or for another reason have no chance of becoming pregnant) not protected by highly effective contraceptive method of birth control as defined for contraception in the Informed Consent Form and /or in a local protocol addendum.
Related to chemotherapy 13.History of hypersensitivity to docetaxel, or polysorbate 80. 14.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) 15.Contraindications to the use of corticosteroid treatment. 16.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) |
Overall survival (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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Same drug, different dose |
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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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 78 |
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 988 deaths are observed in the study. |
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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 | 6 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |