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 12weeks (four courses) and no other prostate cancer treatments between docetaxel andrandomization, 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 forsystemic treatment as judged by the medical care provider
8. Evidence of progressive metastatic disease by PSA progression (Prostate Cancer WorkingGroup 3 (PCWG3) criteria20: at least 2 rises at a minimum of 1-week intervals. Thefirst PSA value must be ≥ 2 ng/ml) and/or radiological progression as evaluated bychest, abdominal, or pelvic CT/MRI scan and/or bone scan within 28 days ofregistration (see Appendix III)
9. Poor prognosis disease as defined by any of the following:
10. The presence of liver metastases AND/OR
11. Development of castration-resistance within 12 months of orchiectomy orcommencement of LHRH antagonist/agonist for metastatic disease AND/OR
12. Progressive disease during docetaxel treatment or <6 months after completion ofdocetaxel treatment
13. World Health Organization Performance Status (WHO PS) 0-2.
14. Serum testosterone < 50 ng/dL (< 1.7 nmol/L) within 28 days before treatment groupallocation
15. At least 21 days have passed since completing radiotherapy (exception for a singlefraction of ≤ 800 centi-Gray (cGy) to a restricted field or limited-field radiotherapyto non-marrow bearing area such as an extremity or orbit: at least 7 days prior torandomization).
16. At least 21 days have passed since major surgery.
17. Neuropathy ≤ grade 1 at the time of registration.
18. Has recovered from all therapy-related toxicity to ≤ grade 2 (except alopecia, anemiaand any signs or symptoms of androgen deprivation therapy) at the time ofregistration.
19. Eligible for cabazitaxel, abiraterone acetate or enzalutamide as per standard of carepractices.
20. Men treated with cabazitaxel should use effective contraception throughout treatmentand are recommended to continue this for up to 6 months after the last dose ofcabazitaxel. Due to potential exposure via seminal liquid, men treated withcabazitaxel should prevent contact with the ejaculate by another person throughouttreatment. Men being treated with cabazitaxel are advised to seek advice onconservation 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 ORenzalutamide sequence
3. Uncontrolled severe illness or medical condition (including uncontrolled diabetesmellitus).
4. History of severe hypersensitivity reaction (≥ grade 3) to docetaxel, abiraterone orenzalutamide (whichever applies).
5. History of severe hypersensitivity reaction (≥ grade 3) to polysorbate 80 containingdrugs.
6. Concurrent or planned treatment with strong inhibitors or strong inducers ofcytochrome P450 3A4/5 (a one week wash-out period is necessary for patients who arealready on these treatments).
7. Patients who have a concurrent yellow fever vaccination (several weeks before start oftreatment) must be excluded.
8. Dementia, altered mental status, or any psychiatric condition, if this is in conflictwith 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 cancersthat have been apparently cured and needing no subsequent therapy.
13. Inadequate organ and bone marrow function as evidenced by:
14. Hemoglobin <10.0 g/dL
15. Absolute neutrophil count <1.5 x 109/L
16. Platelet count < 100 x 109/L
17. aspartate aminotransferase (AST)/ serum glutamate oxaloacetate transaminase (SGOT) and/ or Alanine Aminotransferase (ALT)/ serum glutamate pyruvatetransaminase (SGPT) > 1.5 x (upper limit of normal) ULN Total bilirubin >1 x ULN (except for patients with documented Gilbert's disease).