OZM-054: This phase II trial is comparing Cabazitaxel (a chemotherapy drug) with Abiraterone (a new type of hormone therapy) and Enzalutamide (an oral drug) for the treatment of castration-resistant prostate cancers that express poor outcomesA Phase II, Randomized, Multi-center Study of Cabazitaxel Versus Abiraterone or Enzalutamide in Poor Prognosis-metastatic Castration-resistant Prostate Cancer

Inclusion

• 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.