Title
A Randomized Phase III Clinical Trial For the Addition of Docetaxel to Androgen Receptor Pathway Inhibitors in Patients with Metastatic Castration Sensitive Prostate Cancer and Suboptimal PSA Response (TRIPLE-SWITCH)

Description
This study is being done to answer the following question: can the chance of prostate cancer growing or spreading be lowered by adding a drug to the usual combination of drugs?

This study would like to find out if this approach is better or worse than the usual approach for prostate cancer.

The usual approach for patients who are not in a study is hormone treatment with Androgen Deprivation Therapy (ADT) and Androgen-Receptor Pathway Inhibitor (ARPI).

Objective
Primary Objective:
To compare overall survival (OS) in participants with mCSPC who are receiving standard of care ADT (between 6-12 months exposure) + ARPI (>= 4-months exposure) and have suboptimal PSA response (PSA >= 0.2 ng/ml at enrollment) with those who receive standard of care ADT + ARPI plus docetaxel chemotherapy.

Secondary Objectives:
To compare both arms with respect to:
- PSA progression
- PSA response (PCWG3 criteria)
- PSA kinetics: 90% PSA decline; PSA <0.2ng/ml; PSA <0.02ng/ml
- Clinical progression free survival

Treatment This is an international multi-centre, open-label, randomized phase III trial comparing Docetaxel chemotherapy added to standard of care Androgen Deprivation Therapy (ADT) + Androgen-Receptor Pathway Inhibitor (ARPI) versus standard of care Androgen Deprivation Therapy (ADT) + Androgen-Receptor Pathway Inhibitor (ARPI) in participants with metastatic castration sensitive prostate cancer (mCSPC) who have a suboptimal PSA response after 6-12 months of androgen-targeting therapy.

Key Eligibility Inclusion Criteria:

- Histologically/cytologically confirmed adenocarcinoma of the prostate or participants with a PSA >100 ng/ml (100 ug/L) and radiographic evidence of metastatic disease at diagnosis.
- Metastatic disease by conventional imaging (bone scan or CT and/or MRI or PSMA-PET scan at the time of ADT initiation.
- PSA of >= 2.0 ng/ml (2.0 ug/L) prior to commencement of ADT (this refers to patients who have histologically/cytologically confirmed adenocarcinoma of the prostate)
- Patients will have recovered from any treatment-related toxicities prior to enrollment (unless ≤ grade 1, irreversible, or considered by investigator as not clinically significant).
- Patients may enroll with persistent toxicities attributable to ADT, including hot flushes and fatigue, of any grade, provided these toxicities are clinically stable, not rapidly worsening, and not considered by the Investigator to pose a safety risk or impair the patient's ability to comply with study procedures. Such toxicities do not need to resolve to Grade <=1 prior to study entry.
- Receipt of ADT for mCSPC for at least 6 months and no greater than 12 months (+/- 3 weeks) at time of enrollment.
- Receipt of ARPI (e.g. abiraterone acetate, enzalutamide, apalutamide, or darolutamide) for at least 4 months (+/- 2 weeks) at time of enrollment
- Patients may have had radiotherapy to prostatic bed and/or metastatic sites prior to enrollment. Potential trial participants should have recovered from radiotherapy-related toxicities prior to enrollment.
- Serum testosterone <1.7 nmol/L or 50 ng/dL.
- PSA >= 0.2 ng/ml (0.2 ug/L) within 28 days of enrollment.
- Candidate for docetaxel chemotherapy
- ECOG Performance Status (PS) 0 to 2.
- Adequate organ and marrow function measured within 28 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 10 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

Applicable Disease Sites
Prostate

Participating Institutions
UW Health Eastpark Medical Center; UW Health University Hospital