Cabazitaxel at 20 mg/m² Compared to 25 mg/m² With Prednisone for the Treatment of Metastatic Castration Resistant Prostate Cancer
Condition: Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: Cabazitaxel (XRP6258); Prednisone (or Prednisolone)
Intervention description: Pharmaceutical form: Concentrate and solvent for solution for infusion
Route of administration: Intravenous; Pharmaceutical form: Tablet
Route of administration: Oral
Intervention MeSH terms: Prednisone; Prednisolone
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 1200.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Primary Objective:

      - 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 participants
      with metastatic castration resistant prostate cancer (mCRPC) previously treated with a
      docetaxel-containing regimen.

      Secondary Objectives:

        -  To evaluate safety in the 2 treatment arms and to assess if Cabazitaxel 20 mg/m² was
           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), prostate-specific antigen (PSA) progression, pain progression or
                death due to any cause;

             -  PSA Progression;

             -  Pain progression;

             -  Tumor response in participants with measurable disease (RECIST 1.1);

             -  PSA response;

             -  Pain response in participants with stable pain at baseline.

        -  To compare Health-related Quality of Life (HRQoL).

        -  To assess the pharmacokinetics and pharmacogenomics of Cabazitaxel.
    

Eligibility criteria:

        Inclusion criteria :

        I 01. Diagnosis of histologically or cytologically proven prostate adenocarcinoma, that was
        resistant to hormone therapy and previously treated with a docetaxel-containing regimen.

        I 02. Participant must had either measurable or non-measurable disease. I 03. 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.

        I 04. Life expectancy > 6 months. I 05. Eastern Cooperative Oncology Group (ECOG)
        performance status (PS) 0 - 2 (i.e, participant must be ambulatory, capable of all
        self-care, and up and about more than 50% of waking hours).

        I 06. Age ≥18 years (or country's legal age of majority if the legal age was > 18 years).

        Exclusion criteria:

        E 01. Previous treatment with mitoxantrone or cabazitaxel. E 02. Prior isotope therapy or
        radiotherapy to ≥30% of bone marrow. In case of prior isotope therapy 12 weeks must had
        elapsed prior to first study drug administration.

        E 03. 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 04. Prior surgery, radiation, chemotherapy, or other anti-cancer therapy within 4 weeks
        prior to enrollment in the study.

        E 05. Prior malignancy. Adequately treated basal cell or squamous cell skin or superficial
        (pTis, pTa, and pT1) bladder cancer were allowed, as well as any other cancer for which
        chemotherapy had been completed ≥ 5 years ago and from which the participant had been
        disease-free for ≥ 5 years.

        E 06. Participation in another clinical trial and any concurrent treatment with any
        investigational drug within 30 days prior to randomization.

        E 07. Known brain or leptomeningeal involvement. E 08. Other concurrent serious illness or
        medical conditions. E 09. Uncontrolled cardiac arrhythmias, angina pectoris, and/or
        hypertension. History of congestive heart failure (NYHA III or IV) or myocardial infarction
        within last 6 months was also not allowed.

        E 10. Any severe acute or chronic medical condition which could impair the ability of the
        participant to participate to the study or to comply with the study procedures or interfere
        with interpretation of study results.

        E 11. Absence of signed and dated Institutional Review Board (IRB)-approved participant
        informed consent form prior to enrollment into the study.

        E 12. Participants with reproductive potential who did not agree to use accepted and
        effective method of contraception during the study treatment period. The definition of
        "effective method of contraception" was based on the Investigator's judgment. Participant's
        Partners of childbearing potential (unless surgically sterile, post menopausal or for
        another reason had 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.

        E 13. History of hypersensitivity to docetaxel, or polysorbate 80. E 14. Inadequate organ
        and bone marrow function. E 15. Contraindications to the use of corticosteroid treatment. E
        16. Symptomatic peripheral neuropathy grade > 2 (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.