Cabazitaxel Versus the Switch to Alternative AR Targeted Therapy Enzalutamide or Abiraterone in Metastatic Castration-Resistant Prostate Cancer (mCRPC) Primary Resistant Patients to Abiraterone or Enzalutamide

The duration of the study per patient will be approximately 2 years. Each patient will be
treated until radiographic disease progression, unacceptable toxicity, or patient's refusal
of further study treatment, and each patient will be followed after completion of study
treatment until death, study cutoff date, or withdrawal of patient consent.

Inclusion criteria:

- Diagnosis of histologically or cytologically confirmed prostate adenocarcinoma.

- Metastatic disease.

- Progressive disease (PD) while receiving AR targeted therapy with abiraterone acetate
or enzalutamide within 12 months of treatment initiation (≤12 months) by at least one
of the following:

- Progression in measurable disease Response Evaluation Criteria in Solid Tumors
(RECIST) 1.1.

- Appearance of 2 or more new bone lesions according to Prostate Cancer Working Group 2
(PCWG2).

- Rising PSA defined (PCWG2).

- A PSA value of at least 2 ng/mL is required at study entry.

- Effective castration (serum testosterone levels ≤0.5 ng/mL).

- Prior AR targeted therapy (abiraterone acetate or enzalutamide) must be stopped at
least 2 weeks before study treatment.

- Signed written informed consent.

Exclusion criteria:

- Prior chemotherapy for prostate cancer, except estramustine and except
adjuvant/neoadjuvant treatment completed >3 years ago. No further anti-cancer therapy
after the previous AR targeted therapy and before inclusion. Prior docetaxel in
hormone sensitive setting is allowed if completed >1 year before randomization. Prior
immunotherapy is allowed.

- Less than 28 days elapsed from prior treatment with 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 for Adverse Events [NCI CTCAE] v4.0) at the time of
randomization.

- Eastern Cooperative Oncology Group (ECOG) performance status >1.

- History of brain metastases, uncontrolled spinal cord compression, or carcinomatous
meningitis, or new evidence of brain or leptomeningeal disease.

- 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
treatment has been completed ≥5 years ago and from which the patient 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.

- Any severe acute or chronic medical condition including uncontrolled diabetes
mellitus, severe renal impairment, history of cardiovascular disease (uncontrolled
hypertension, arterial thrombotic events in the past 6 months, congestive heart
failure, severe or unstable angina pectoris, recent myocardial infraction within last
6 months or uncontrolled cardiac arrhythmia), which could impair the ability of the
patient to participate to the study or interfere with interpretation of study results,
or patient unable to comply with the study procedures.

- Patients with reproductive potential who do not agree 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" will be
based on the Investigator's judgment.

- Known allergies, hypersensitivity or intolerance to prednisone or excipients of
abiraterone acetate or enzalutamide. History of hypersensitivity to docetaxel or
polysorbate 80.

- Known history of mineralocorticoid excess or deficiency (not applicable to patients
who have already been treated with abiraterone acetate in first line before
inclusion).

- History of seizure, underlying brain injury with loss of consciousness, transient
ischemic attack within the past 12 months, cerebral vascular accident, brain
arteriovenous malformation or the use of concomitant medications that may lower the
seizure threshold (not applicable to patients who have already been treated with
enzalutamide in first line before inclusion).

- 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 x 10^9/L.

- Platelet count <100 x 10^9/L.

- Aspartate aminotransferase (AST) and/or Alanine aminotransferase (ALT) >1.5 x Upper
limit of normal (ULN).

- Total bilirubin >1.0 x ULN.

- Potassium <3.5 mmol/L.

- Serum albumin <3.0 g/dL.

- Child-Pugh Class B and C.

- Contraindications to the use of corticosteroid treatment.

- Symptomatic peripheral neuropathy grade ≥2 NCI CTCAE v4.0.

- Concomitant vaccination with yellow fever vaccine.

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