Prostate Cancer (Adenocarcinoma)
Conditions
Keywords
PR26, Castration sensitive
Brief summary
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).
Detailed description
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.
Interventions
DRUGAbiraterone
Assigned prior to enrollment
DRUGEnzalutamide
Assigned prior to enrollment
DRUGApalutamide
Assigned prior to enrollment
Assigned prior to enrollment
DRUGDocetaxel
Assigned at enrollment
DRUGADT
Physician's choice. Assigned prior to enrollment
Sponsors
Canadian Cancer Trials Group
ECOG-ACRIN Cancer Research Group
NRG Oncology
Alliance for Clinical Trials in Oncology
SWOG Cancer Research Network
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Exclusion criteria
* Confirmed PSA progression, defined by an increase in PSA of 25% above the nadir since achieving castration on ADT, an absolute increase in PSA value of 2.0 ng/ml (ug/L) above nadir, and a subsequent increase in PSA of 25% further separated by 3 or more weeks. * Evidence of confirmed radiographic progression or clinical progression since start of ADT. Participants may be enrolled on the study if, in the opinion of the investigator, any new bone lesions on bone scan and CT represent flare or treatment effect. * Docetaxel criteria: * Prior treatment with taxane chemotherapy * Grade 2 or worse peripheral neuropathy * Severe hypersensitivity to drugs formulated with polysorbate 80 * Clinically significant cardiac disease including: * History of unstable angina pectoris, symptomatic pericarditis, or myocardial infarction within 6 months prior to study entry. * History of documented congestive heart failure (New York Heart Association functions classification III-IV). * 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 (except if a participant has no histological diagnosis but a PSA \>100 ng/ml (\>100 ug/L) at diagnosis and radiographic evidence of metastatic disease)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Overall Survival | 39 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PSA Progression compared in both arms | 39 months | — |
| PSA Response comparison between arms | 39 months | PCWG3 criteria |
| PSA Kinetics compared between both arms | 39 months | * 90% PSA decline * PSA \<0.2ng/ml * PSA \<0.02ng/ml |
| Clinical progression-free survival between both arms | 39 months | — |
Countries
Canada, Mexico, United States, Uruguay
Contacts
CONTACTMariam Jafri
CONTACTWendy Parulekar
STUDY_CHAIRMichael Ong
Ottawa Hospital Research Institute, Ottawa ON Canada
STUDY_CHAIRAlexandra Sokolova
Oregon Health and Science University, Portland, OR, USA
Outcome results
None listed