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 time of enrollment.
* Receipt of ARPI (e.g. abiraterone acetate, enzalutamide, apalutamide, or darolutamide) for at least 4 months at time of enrollment
* Potential trial participants should have recovered from clinically significant adverse 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 PSA since starting ADT and achieving castrate-level testosterone, PSA must be repeated and 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 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 5 working days of participant enrollment.
* If the participant and the participant's partner are of childbearing potential, they must agree to use medically accepted methods of contraception
* HIV-infected participants on effective anti-retroviral therapy with undetectable viral 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 weeks apart with at least one PSA ≥5% above the PSA nadir and with at least one PSA having an 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 of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class II or better.
* Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make this protocol unreasonably hazardous.
* Patients with a prior or concurrent malignancy whose natural history of treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
* Concurrent treatment with other anti-cancer systemic therapy other than ADT and ARPI.
* Live attenuated vaccination administered within 30 days prior to enrollment/randomization.
* For participants with a history of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
* Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
* High-grade neuroendocrine prostate cancer or small cell features.