The purpose of this study is to assess and compare the clinical benefit rate in patients with metastatic castrate-resistant prostate cancer and poor prognostic factors treated with cabazitaxel or novel hormonal agents (abiraterone or enzalutamide) as initial therapy, to determine which treatment is most active in this population. Clinical benefit rate is defined as PSA or measurable radiological response of any duration or stable disease for > or equal to 12 weeks, in the absence of other indicators of progression.

There is option to cross-over onto the other arm if the patient progresses.

Inclusion Criteria:

• Histological diagnosis of prostate adenocarcinoma.
• Able and willing to provide informed consent and to comply with the study procedures
• Age ≥18
• Evidence of metastatic disease on a chest, abdominal, or pelvic CT scan and/or bone scan within 6 weeks of registration
• Castration resistant disease defined as evidence of radiological and/or PSA progression despite castrate levels of testosterone (serum testosterone < 50 ng/dL (1.7 nmol/L)). For PSA progression, there must be at least 2 sequential rises at a minimum of 1-week intervals. The first PSA value must be ≥ 2. (Prostate Cancer Working Group 2 (PCWG2) criteria)
• Poor prognosis disease as defined by any of the following:

the presence of liver metastases OR development of castration-resistance within 12 months of orchiectomy or commencement of LHRH antagonist/agonist for metastatic disease OR the presence of 4 or more of the following factors:

• LDH > ULN
• ECOG Performance status (PS) 2
• visceral metastatic disease
• serum albumin less than or equal to 4 g/dL
• ALP > ULN
• or < 36 months from commencement of initial androgen deprivation therapy to study enrollment
• ECOG PS 0-2.
• Adequate end-organ function within 14 days of registration:

Haemoglobin ≥ 90 g/L Neutrophils ≥ 1.5 x 109 /L Platelets ≥ 100 x 109/L AST < 1.5 x ULN ALT < 1.5 x ULN Bilirubin ≤ 1.0 x ULN (exceptions for Gilbert's syndrome) Creatinine ≤ 1.5 x ULN

• At least 21 days have passed since completing radiotherapy (exception for radiotherapy: at least 7 days since completing a single fraction of ≤ 800 cGy to a restricted field or limited-field radiotherapy to non-marrow bearing area such as an extremity or orbit) at the time of randomization.
• At least 21 days have passed since receiving any investigational agent at the time of registration.
• At least 21 days have passed since major surgery.
• Neuropathy ≤ grade 1 at the time of registration.
• Has recovered from all therapy-related toxicity to ≤ grade 2 (except alopecia, anemia and any signs or symptoms of androgen deprivation therapy) at the time of registration.
• Eligible for abiraterone acetate and/or enzalutamide as per standard of care practices.

Exclusion Criteria:

• Histologic evidence of small cell/neuroendocrine prostate cancer.
• Other chemotherapy regimen beyond one prior course of docetaxel.
• Previously received treatment with cabazitaxel.
• Received any prior next-generation anti-androgen (e.g. enzalutamide, ARN-509) or CYP 17 inhibitors (e.g. abiraterone, TAK-700).
• Other condition, illness, psychiatric condition, or laboratory abnormality that may increase the risk associated with administration of cabazitaxel, abiraterone or enzalutamide, study participation, or may interfere with the interpretation of study results and in the judgment of the investigator would make the patient inappropriate for entry into this study.