Docetaxel to Androgen Receptor Pathway Inhibitors in Patients With Metastatic Castration Sensitive Prostate Cancer and Suboptimal PSA Response

Inclusion Criteria:

• Histologically/cytologically confirmed adenocarcinoma of the prostate

• Metastatic disease by conventional imaging

• PSA of ≥5.0 ng/ml (5.0 ug/L) prior to commencement of ADT

• Receipt of ADT for mCSPC for at least 6 months and no greater than 12 months at timeof enrollment.

• Receipt of ARPI (e.g. abiraterone acetate, enzalutamide, apalutamide, ordarolutamide) for at least 4 months at time of enrollment

• Potential trial participants should have recovered from clinically significantadverse events of their most recent therapy/intervention prior to enrollment.

• Serum testosterone <1.7 nmol/L or 50 ng/dL.

• PSA ≥ 0.2 ng/ml (0.2 ug/L) within 14 days of enrollment. If there is any rise in PSAsince starting ADT and achieving castrate-level testosterone, PSA must be repeatedand must not fulfill ineligibility criteria 4.2.1.

• Candidate for docetaxel chemotherapy

• ECOG Performance Status (PS) 0 to 2.

• Adequate organ and marrow function measured within 14 days prior to enrollment.

• 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 5 working daysof participant enrollment.

• If the participant and the participant's partner are of childbearing potential, theymust agree to use medically accepted methods of contraception

• HIV-infected participants on effective anti-retroviral therapy with undetectableviral load within 6 months are eligible for this trial.

• Participant access to all protocol therapies must be confirmed prior to enrollment

Exclusion Criteria:

• Two consecutive rises in PSA since achieving castration on ADT at least 2 weeksapart with at least one PSA ≥5% above the PSA nadir and with at least one PSA havingan absolute increase of ≥0.5 ng/ml above the PSA nadir.

• Evidence of radiographic progression or clinical progression since start of ADT.

• Docetaxel criteria:

• Prior treatment with taxane chemotherapy

• Grade 2 or worse peripheral neuropathy

• Severe hypersensitivity to drugs formulated with polysorbate 80

• Patients with known history or current symptoms of cardiac disease, or history oftreatment with cardiotoxic agents, should have a clinical risk assessment of cardiacfunction using the New York Heart Association Functional Classification. To beeligible for this trial, patients should be class II or better.

• Patients with uncontrolled intercurrent illness or any other significantcondition(s) that would make this protocol unreasonably hazardous.

• Patients with a prior or concurrent malignancy whose natural history of treatmentdoes not have the potential to interfere with the safety or efficacy assessment ofthe investigational regimen are eligible for this trial.

• Concurrent treatment with other anti-cancer systemic therapy other than ADT andARPI.

• Live attenuated vaccination administered within 30 days prior toenrollment/randomization.

• For participants with a history of chronic hepatitis B virus (HBV) infection, theHBV viral load must be undetectable on suppressive therapy, if indicated.

• Participants with a history of hepatitis C virus (HCV) infection must have beentreated and cured. For participants with HCV infection who are currently ontreatment, they are eligible if they have an undetectable HCV viral load.

• High-grade neuroendocrine prostate cancer or small cell features.