Cabazitaxel Versus Docetaxel Both With Prednisone in Patients With Metastatic Castration Resistant Prostate Cancer

Randomized, Open Label, Multi-Center Study Comparing Cabazitaxel at 25 mg/m^2 and at 20 mg/m^2 in Combination With Prednisone Every 3 Weeks to Docetaxel in Combination With Prednisone in Patients With Metastatic Castration Resistant Prostate Cancer Not Pretreated With Chemotherapy

Primary Objective:

• To demonstrate the superiority of cabazitaxel plus prednisone at 25 mg/m^2 (Arm A) or 20 mg/m^2 (Arm B) versus docetaxel plus prednisone (Arm C) in term of overall survival (OS) in participants with metastatic castration resistant prostate cancer (mCRPC) and not previously treated with chemotherapy.

Secondary Objectives:

• To evaluate safety in the 3 treatment arms.

• To compare efficacy of cabazitaxel at 20 mg/m^2 and 25 mg/m^2 to docetaxel for:

  • Progression Free Survival (PFS) (RECIST 1.1)
  • Tumor progression free survival (RECIST 1.1)
  • Tumor response in participants with measurable disease (RECIST 1.1),
  • PSA response
  • PSA-Progression free survival (PSA-PFS).
  • Pain response in participants 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 pharmacokinetics and pharmacogenomics of cabazitaxel.

Participants were treated until progressive disease, unacceptable toxicity, or participant's refusal of further study treatment. All participants were followed when on study treatment and after completion of study treatment during follow up period until death or the study cutoff date, whichever comes first.

Inclusion criteria :

• I 01. Histologically- or cytologically-confirmed prostate adenocarcinoma.
• I 02. Metastatic disease.
• I 03. Progressive disease while receiving hormonal therapy or after surgical castration.
• I 04. Effective castration (serum testosterone levels ≤0.50 ng/mL) by orchiectomy and/or luteinizing hormone-releasing hormone (LHRH) agonists or antagonist with or without anti-androgens.

Exclusion criteria:

• E 01. Prior chemotherapy for prostate cancer,
• E 02. Less than 28 days elapsed from prior treatment with estramustine, radiotherapy or surgery to the time of randomization. Participants on biphosphonates prior to study entry.
• E 03. Prior isotope therapy, whole pelvic radiotherapy, or radiotherapy to >30% of bone marrow.
• E 04. 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.
• E 05. Less than 18 years (or country's legal age of majority if the legal age is >18 years).
• E 06. Eastern Cooperative Oncology Group (ECOG) performance status >2.
• E 07. History of brain metastases, uncontrolled spinal cord compression, or carcinomatous meningitis or new evidence of brain or leptomeningeal disease.
• E 08. Prior malignancy.
• E 09. Participation in another clinical trial and any concurrent treatment with any investigational drug within 30 days prior to randomization.
• E 10. Any of the following within 6 months prior to study enrollment: myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, New York Heart Association (NYHA) class III or IV congestive heart failure, stroke or transient ischemic attack.
• E 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.
• E 12. Acquired immunodeficiency syndrome (AIDS-related illnesses) or known HIV disease requiring antiretroviral treatment.
• E 13. Any severe acute or chronic medical condition which could impair the ability of the participant to participate to the study or interfere with interpretation of study results, or participants unable to comply with the study procedures.
• E 14. Absence of signed and dated Institutional Review Board (IRB)-approved participant informed consent form prior to enrollment into the study.
• E 15. Participants with reproductive potential who did not agree to use accepted and effective method of contraception during the study treatment period.
• E 16. History of hypersensitivity to docetaxel, or polysorbate 80.
• E 17. Inadequate organ and bone marrow function
• E 18. Contraindications to the use of corticosteroid treatment.
• E 19. Symptomatic peripheral neuropathy grade >2 (National Cancer Institute Common Terminology Criteria [NCI CTCAE] v.4.03).

The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.