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

Inclusion Criteria:

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

• Prior treatment with any ARPI, such as abiraterone, enzalutamide, apalutamide, ordarotlutamide, is required.

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

• Longest of one of the following:

• Two weeks or 5 half lives (whichever is longer) for oral therapies (such asabiraterone, apalutamide, enzalutamide, darolutamide and olaparib)

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

• 2 weeks, 5 half lives, or standard cycle length (whichever is longer) forinvestigational agents

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

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

• Radiologically documented presence of metastatic disease within 28 days prior torandomization

• Disease progression after ARPI therapy as assessed by the investigator with at leastone of the following:

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

• Radiographic progression of soft tissue disease by RECIST 1.1 criteria or bonemetastases 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 significantor pathogenic / likely pathogenic) germline or somatic alterations involving one ormore 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 daysprior to enrolment

• Life expectancy > 12 weeks.

• If the participant and the participant's partner are of childbearing potential, theymust agree to use medically accepted methods of contraception (e.g., barriermethods, 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 qualityof life and health utility questionnaires in either English or French

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

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

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

Exclusion Criteria:

• Received prior platinum chemotherapy (i.e. carboplatin, cisplatin, oxaliplatin,satraplatin) at any time; received prior taxane chemotherapy (docetaxel, paclitaxel,cabazitaxel) with the exception of docetaxel for mCSPC as long as it was no morethan 6 cycles and at least 12 months have elapsed from their last treatment to thedate of enrollment.

• Active anticancer systemic therapy or investigational agents within 14 days ofrandomization.

• Uncontrolled intercurrent illness including, but not limited to: active infection,symptomatic congestive heart failure (NYHA Class III or IV heart disease), unstableangina pectoris, cardiac arrhythmia, uncontrolled hypertension or psychiatricillness/social situations that would limit compliance with study requirements.

• Participants with myelodysplastic syndrome/acute myeloid leukemia.

• Malignancy within the previous 2-years with a > 30% probability of recurrence within 12 months, with the exception of non-melanoma skin cancer, and in-situ orsuperficial bladder cancer.

• Participants with known symptomatic brain metastasis. However, participants withasymptomatic, treated brain metastases that have been stable for at least 12 weeksare eligible for study entry.

• Participants with symptomatic or impending cord compression unless appropriatelytreated beforehand and clinically stable and asymptomatic.

• Presence of a condition or situation, which, in the investigator's opinion, may putthe participant at significant risk, may confound the study results, or mayinterfere significantly with participation in the study.

• Live attenuated vaccination administered within 30 days prior to randomization.

• For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBVviral load must be undetectable on suppressive therapy, if indicated. Participantswith a history of hepatitis C virus (HCV) infection must have been treated andcured. For participants with HCV infection who are currently on treatment, they areeligible if they have an undetectable HCV viral load.

• Unable to obtain provincial reimbursement of carboplatin and docetaxel