Cabazitaxel Versus the Switch to Alternative AR-targeted Agent (Enzalutamide or Abiraterone) in Metastatic Castration-resistant Prostate Cancer (mCRPC) Patients Previously Treated With Docetaxel and Who Rapidly Failed a Prior AR-targeted Agent
Condition: Prostate Cancer Metastatic
MeSH terms: Prostatic Neoplasms
Intervention: cabazitaxel XRP6258; enzalutamide; abiraterone acetate; prednisone
Intervention description: Pharmaceutical form: solution Route of administration: intravenous; Pharmaceutical form: capsule Route of administration: oral; Pharmaceutical form: tablet Route of administration: oral; Pharmaceutical form: tablet Route of administration: oral
Intervention MeSH terms: Prednisone; Abiraterone Acetate
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 255.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Primary Objective:

      To compare the radiographic progression-free survival (rPFS) (using Response Evaluation
      Criteria in Solid Tumors [RECIST] 1.1 for tumor lesions and Prostate Cancer Working Group 2
      (PCWG2) criteria for bone scan lesions or death due to any cause) with chemotherapy
      (cabazitaxel plus prednisone, Arm A) versus Androgen Receptor (AR)-targeted therapy
      (enzalutamide or abiraterone acetate plus prednisone, Arm B) in mCRPC participants who have
      been treated with docetaxel and who had disease progression while receiving AR-targeted
      therapy within 12 months of AR treatment initiation (less than or equal to [<=]12 months,
      either before or after docetaxel).

      Secondary Objective:

        -  To compare efficacy for:

        -  Prostate-specific antigen (PSA) response rate and time to PSA progression (TTPP).

        -  Progression-free survival (PFS).

        -  Overall survival (OS).

        -  Tumor response rate and duration of tumor response.

        -  Pain response and time to pain progression.

        -  Symptomatic skeletal event (SSE) rate and time to occurrence of any SSE.

        -  Health status and Health-related Quality of Life (HRQOL).

        -  To evaluate the correlation of a signature of resistance to AR-targeted agents with
           clinical outcome via the analysis of circulating tumor cell (CTC) phenotypes as well as
           expression and localization of proteins including AR isoforms in CTCs.

        -  To evaluate safety in the 2 treatment arms.
    

Eligibility criteria:

        Inclusion criteria :

        Histologically confirmed prostate adenocarcinoma.

          -  Metastatic disease.

          -  Effective castration with serum testosterone levels less than (<)0.5 ng/mL. If the
             participant has been treated with Luteinizing hormone-releasing hormone agonist (LHRH)
             agonists or antagonist (i.e., without orchiectomy), then this therapy should be
             continued.

          -  Progressive disease defined by at least one of the following:

          -  Progression in measurable disease (RECIST 1.1 criteria).

          -  Appearance of 2 or more new bone lesions (PCWG2).

          -  Rising Prostate Specific Antigen (PSA) (PCWG2).

          -  Having received prior docetaxel for at least 3 cycles (before or after an AR-targeted
             therapy). Docetaxel administration in combination with androgen deprivation therapy
             (ADT) in metastatic hormone-sensitive disease was considered a prior exposure.
             Docetaxel rechallenge was allowed.

          -  Having progressive disease (PD) while receiving AR-targeted therapy with abiraterone
             acetate or enzalutamide within 12 months of AR treatment initiation (<=12 months),
             even if treatment duration was longer than 12 months. Participants treated with
             Abiraterone Acetate + ADT in metastatic hormone-sensitive setting were eligible in the
             study if they have progressed within 12 months with the AR-targeted agent.
             Participants having PSA progression only (as per PCWG2) within 12 months were
             eligible.

          -  A PSA value of at least 2 ng/mL was required at study entry.

          -  Prior AR-targeted therapy (abiraterone acetate or enzalutamide) must be stopped at
             least 2 weeks before study treatment.

          -  Signed informed consent.

        Exclusion criteria:

          -  Prior chemotherapy other than docetaxel for prostate cancer, except estramustine and
             except adjuvant/neoadjuvant treatment completed >3 years ago.

          -  Less than 28 days elapsed from prior treatment with chemotherapy, immunotherapy,
             radiotherapy, or surgery to the time of randomization.

          -  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] v4.0) at the time of randomization.

          -  Eastern Cooperative Oncology Group performance status (ECOG PS) >2 (ECOG 2 must be
             related to prostate cancer, not to other comorbidities).

          -  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 treatment has been completed >=5 years ago and from which the participant has
             been disease-free for >=5 years.

          -  Participation in another clinical trial and any concurrent treatment with any
             investigational drug within 30 days prior to randomization.

          -  Acquired immunodeficiency syndrome (AIDS-related illnesses) or known human
             immunodeficiency virus (HIV) disease requiring antiretroviral treatment.

          -  Participants with reproductive potential who do not agree, in conjunction with their
             partner, to use accepted and effective method of contraception during the study
             treatment period and up to 6 months after the last administered dose. The definition
             of "effective method of contraception" described hereafter: oral contraceptives,
             combined hormonal intravaginal, transdermal, intra uterine device or condoms was based
             on respective study treatment labelling and country-specific regulatory requirements,
             and were documented in the Informed Consent Form.

          -  Known allergies, hypersensitivity or intolerance to prednisone or excipients of
             abiraterone acetate, enzalutamide, docetaxel, or polysorbate 80.

          -  Known history of mineralocorticoid excess or deficiency.

          -  History of seizure, underlying brain injury with loss of consciousness, transient
             ischemic attack within the past 12 months, cerebral vascular accident, brain
             arteriovenous malformation, brain metastases, or the use of concomitant medications
             that may lower the seizure threshold.

          -  Unable to swallow a whole tablet or capsule.

          -  Inadequate organ and bone marrow function as evidenced by:

          -  Hemoglobin <10.0 g/dL;

          -  Absolute neutrophil count <1.5 * 10^9/L;

          -  Platelet count <100 * 10^9/L;

          -  Aspartate aminotransferase/serum glutamic oxaloacetic transaminase and/or alanine
             aminotransferase/serum glutamic pyruvic transaminase >1.5 * the upper limit of normal
             (ULN);

          -  Total bilirubin >1.0 * ULN;

          -  Potassium <3.5 mmol/L;

          -  Child-Pugh Class C.

          -  Contraindications to the use of corticosteroid treatment.

          -  Symptomatic peripheral neuropathy Grade >=2 (NCI CTCAE v4.0).

          -  Uncontrolled severe illness or medical condition including uncontrolled diabetes
             mellitus, history of cardiovascular disease (uncontrolled hypertension, arterial
             thrombotic events in the past 6 months, congestive heart failure, severe or unstable
             angina pectoris, recent myocardial infarction within the last 6 months, or
             uncontrolled cardiac arrhythmia).

          -  Concomitant vaccination with yellow fever vaccine.

        The above information was not intended to contain all considerations relevant to a
        participant's potential participation in a clinical trial.