Platinum and Taxane Chemo in Met Castration Resistant Prostate Cancer Patients With Alterations in DNA Damage Response Genes

Histologic diagnosis of adenocarcinoma of the prostate. The presence of neuroendocrine or small cell carcinoma will be exclusionary

Prior treatment with any ARPI, such as abiraterone, enzalutamide, apalutamide, or darotlutamide, is required.

Participants must have recovered to ≤ grade 1 from all reversible toxicity related to prior systemic or radiation therapy, with the exception of chemotherapy induced alopecia and grade 2 peripheral neuropathy, and have adequate washout as follows:

Longest of one of the following:

* Two weeks for oral therapies (such as abiraterone, apalutamide, enzalutamide, darolutamide and olaparib)

* Standard cycle of standard IV or IM therapies (such as radium 223 or Lu-177-PSMA-617

* 2 weeks, 5 half lives, or standard cycle length (whichever is longer) for investigational agents

Previous major surgery is permitted provided that surgery occurred at least 28 days prior to participant enrollment and that wound healing has occurred

Prior external beam radiation is permitted provided a minimum of 7 days have elapsed between the last dose of radiation and date of enrollment

Radiologically documented presence of metastatic disease within 28 days prior to randomization

Disease progression after ARPI therapy as assessed by the investigator with at least one of the following:

PSA progression with a minimum of two rising PSA values at least 1 week apart, at least 25% and 2ug/L above baseline/nadir.

Radiographic progression of soft tissue disease by RECIST 1.1 criteria or bone metastases by PCWG3 criteria.

Medical or surgical castration with serum testosterone levels \<50ng/dL or \<1.7mmol/L

Qualifying Tier I or Tier II (clinically significant/likely clinically significant or pathogenic / likely pathogenic) germline or somatic alterations involving one or more of the following DDR genes: BRCA1, BRCA2, ATM, ATR, BRIP1, BARD1, CDK12, CHEK1, CHEK2, ERCC2, FANCA, FANCC, FANCD2, FANCL, PALB2, RAD51B, RAD51C, RAD51D, RAD54L. Monoallelic gene deletions in isolation will not be eligible.

Age 18 years or older.

Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2

Participants must have adequate organ and marrow function measured within 14 days prior to enrolment

Life expectancy \> 12 weeks.

If the participant and the participant's partner are of childbearing potential, they must agree to use medically accepted methods of contraception (e.g., barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the course of the study and for 6 months after the last dose of study drug.

Participant is able (i.e. sufficiently fluent) and willing to complete the quality of life and health utility questionnaires in either English or French

Participant consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each participant must sign a consent form prior to enrollment in the trial to document their willingness to participate.

Participants must be accessible for treatment and follow-up. Investigators must assure themselves the participants enrolled on this trial will be available for complete documentation of the treatment, adverse events, and follow-up.

In accordance with CCTG policy, protocol treatment is to begin within 2 working days after participant enrolment.

Unable to obtain provincial reimbursement of carboplatin and docetaxel

What this study is about