Bipolar Androgen Therapy + Carboplatin in mCRPC

Inclusion Criteria

• •1. Males with histologically confirmed adenocarcinoma of the prostate
• •2. Confirmed HRD (Homologous recombination defect) in germline and/or somatic DNA analysis (tumour or blood), by a validated assay (see Appendix 1). Mutations in HR genes not listed in appendix 1 will be considered in literature suggests pathogenicity. A maximum of 10 uncharacterised or heterozygous mutations will be included.
• •3. Age ≥ 18 years
• •4. ECOG performance status ≤ 1
• •5. Rising PSA confirmed on two sequential tests ≥1 week apart and a minimum value of 2 ug/L despite castrate levels of testosterone
• •6. Serum testosterone \< 1.7 nmol/L and on an LHRH agent or post orchidectomy ≥ 1 year.
• •7. Washout of ≥ 4 weeks from prior line of treatment, radiotherapy or surgery (aside from LHRH agent)
• •8. Adequate bone marrow function (platelets \> 100 x 109/L, ANC \> 1.5 x 109/L, Hb \>100)
• •9. Adequate liver function (ALT/AST \< 1.5 x ULN, bilirubin \< 2 x ULN)
• •10. Adequate renal function (creatinine clearance \> 50 ml/min)
• •11. Adequate cardiac function and reserve after cardiology assessment
• •12. Archived tissue sample available or willingness to undergo fresh biopsy
• •13. Willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments
• •14. Signed, written informed consent
• •11. Concurrent illness, including severe infection that may jeopardize the ability of the patient to undergo the procedures outlined in this protocol with reasonable safety.
• •12. Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule, including alcohol dependence or drug abuse.