Optimal Sequencing of Treatment Options for Poor Risk mCRPC Previously Treated With Docetaxel

Inclusion Criteria: 1. Histological diagnosis of prostate adenocarcinoma. 2. Able and willing to provide informed consent and to comply with the study procedures 3. Age ≥18 4. Evidence of bone, visceral and/or lymph node metastases on bone scan, CT-scan or MRI. 5. Must have received at least one prior regimen of docetaxel treatment for at least 12 weeks (four courses) and no other prostate cancer treatments between docetaxel and randomization, other than prednisone. 6. Continued androgen deprivation therapy either by luteinizing hormone release hormone (LHRH) agonist/ antagonist or orchiectomy. 7. Treatment with curative intent is not an option and patient has an indication for systemic treatment as judged by the medical care provider 8. Evidence of progressive metastatic disease by PSA progression (Prostate Cancer Working Group 3 (PCWG3) criteria20: at least 2 rises at a minimum of 1-week intervals. The first PSA value must be ≥ 2 ng/ml) and/or radiological progression as evaluated by chest, abdominal, or pelvic CT/MRI scan and/or bone scan within 28 days of registration (see Appendix III) 9. Poor prognosis disease as defined by any of the following: 1. The presence of liver metastases AND/OR 2. Development of castration-resistance within 12 months of orchiectomy or commencement of LHRH antagonist/agonist for metastatic disease AND/OR 3. Progressive disease during docetaxel treatment or \<6 months after completion of docetaxel treatment 10. World Health Organization Performance Status (WHO PS) 0-2. 11. Serum testosterone \< 50 ng/dL (\< 1.7 nmol/L) within 28 days before treatment group allocation 12. At least 21 days have passed since completing radiotherapy (exception for a single fraction of ≤ 800 centi-Gray (cGy) to a restricted field or limited-field radiotherapy to non-marrow bearing area such as an extremity or orbit: at least 7 days prior to randomization). 13. At least 21 days have passed since major surgery. 14. Neuropathy ≤ grade 1 at the time of registration. 15. 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. 16. Eligible for cabazitaxel, abiraterone acetate or enzalutamide as per standard of care practices. 17. Men treated with cabazitaxel should use effective contraception throughout treatment and are recommended to continue this for up to 6 months after the last dose of cabazitaxel. Due to potential exposure via seminal liquid, men treated with cabazitaxel should prevent contact with the ejaculate by another person throughout treatment. Men being treated with cabazitaxel are advised to seek advice on conservation of sperm prior to treatment. Exclusion Criteria: 1. Histologic evidence of small cell/neuroendocrine prostate cancer 2. Any treatment other than prednisone between docetaxel and cabazitaxel/abiraterone OR enzalutamide sequence 3. Uncontrolled severe illness or medical condition (including uncontrolled diabetes mellitus). 4. History of severe hypersensitivity reaction (≥ grade 3) to docetaxel, abiraterone or enzalutamide (whichever applies). 5. History of severe hypersensitivity reaction (≥ grade 3) to polysorbate 80 containing drugs. 6. Concurrent or planned treatment with strong inhibitors or strong inducers of cytochrome P450 3A4/5 (a one week wash-out period is necessary for patients who are already on these treatments). 7. Patients who have a concurrent yellow fever vaccination (several weeks before start of treatment) must be excluded. 8. Dementia, altered mental status, or any psychiatric condition, if this is in conflict with the study. 9. Unable to swallow a whole tablet or capsule 10. Contraindications to the use of corticosteroid treatment 11. Symptomatic peripheral neuropathy Grade ≥2 (see Appendix VIII). 12. Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured and needing no subsequent therapy. 13. Inadequate organ and bone marrow function as evidenced by: 1. Hemoglobin \<10.0 g/dL 2. Absolute neutrophil count \<1.5 x 109/L 3. Platelet count \< 100 x 109/L 4. aspartate aminotransferase (AST)/ serum glutamate oxaloacetate transaminase (SGOT) and/ or Alanine Aminotransferase (ALT)/ serum glutamate pyruvate transaminase (SGPT) \> 1.5 x (upper limit of normal) ULN Total bilirubin \>1 x ULN (except for patients with documented Gilbert's disease).