Abiraterone-Rechallenge Study for CRPC Patients (ABI-RE)

Inclusion Criteria:

1. Written prostate cancer.
2. Adult patients with histological or cytological diagnosis of adenocarcinoma of the prostate.
3. Men with castration-resistant metastatic decline maintained for at least 3 weeks as per PCWG2 criteria).
4. Confirmed biochemical response to prior abiraterone acetate (≥50% PSA Informed Consent (including consent for biomarker studies including the fresh tumour biopsies)
5. Progressive disease according to PCWG2 criteria during prior therapy with standard dose of abiraterone acetate (confirmed increase of PSA ≥25% over nadir) or soft-tissue or bone progression. Patients that have stopped abiraterone acetate for reasons other than progression are not eligible.

6. Documented progression of disease by any of the criteria listed here:

   • PSA
   • Soft tissue
   • Bone scan all as per PCWG2 criteria
7. Patients may have received treatment with docetaxel, enzalutamide or radium-223
8. PSA of ≥10ug/l
9. ECOG performance status 0 - 2
10. At least 3 months (90 days) since stop of prior abiraterone acetate.

Exclusion Criteria:

1. Major surgery within 28 days weeks prior to start of treatment
2. Prior treatment with cabazitaxel or the CYP-17 inhibitor TAK-700/orteronel
3. Any concurrent treatment or prior treatment with an investigational drug within 28 days prior to start of treatment.
4. Known brain or leptomeningeal disease
5. Concurrent use of steroids other than prednisone >10mg/d

6. Inadequate bone marrow and organ function as evidenced by:

   Platelet count <75 x 10 G/L ASAT and/or ALAT ≥ 2.5 x ULN Total bilirubin ≥ 1.5 x ULN (≥ 2.0 x ULN for patients with Gilbert's disease) Hypokalaemia despite adequate supplementation Creatinine Clearance <30ml/min

7. Uncontrolled hypertension or cardiac failure or LVEF <50%

creatinine clearance is to be calculated by using the formula of Cockcroft-Gault in appendix 4 of the protocol