The purpose of the study is to demonstrate superiority of Saruparib (AZD5305) relative to placebo added to a standard radiation therapy (RT) + androgen deprivation therapy (ADT) regimen by assessment of metastases-free survival in participants with high-risk and very high-risk localised/locally advanced prostate cancer with a breast cancer gene mutation (BRCAm).
Approximately, 700 adult participants with localised/locally advanced prostate cancer will be randomized in a 1:1 ratio to receive saruparib or placebo with ADT (+ abiraterone) in one of the following two cohorts: Cohort A: 400 adult participants with newly diagnosed high-risk and very high-risk (localised/locally advanced) prostate cancer who have received primary RT and are receiving continuous ADT, and participants with high-risk biochemical recurrence (BCR) \[including prostate-specific antigen (PSA) persistence\] following a radical prostatectomy who have received salvage RT are receiving continuous ADT. Cohort B: 300 adult participants with newly diagnosed very high-risk (locally advanced) prostate cancer who have received primary RT and who are receiving continuous ADT and abiraterone. All participants will be followed for survival until the end of the study. Independent data monitoring committee (DMC) composed of experts will be convened to confirm the safety and efficacy of Saruparib + ADT (+ abiraterone).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
700
Metastasis-free survival (MFS)
MFS is defined as the time from randomisation until the date of first appearance of distant metastases, confirmed by standard clinical imaging \[computed tomography (CT)/ magnetic resonance imaging (MRI) and bone scan, or prostate-specific membrane antigen-positron emission tomography (PSMA-PET)\], as assessed by blinded independent central review (BICR) or death due to any cause.
Time frame: Up to approximately 93 months
Overall Survival (OS)
OS is defined as the time from randomisation until the date of death due to any cause.
Time frame: Up to approximately 11 years
MFS (CT/MRI and bone scan)
MFS is defined as the time from randomisation until the date of distant metastases, confirmed by conventional imaging (CT/MRI and bone scan), or death due to any cause.
Time frame: Up to approximately 93 months
MFS (PSMA-PET)
MFS is defined as the time from randomisation until the date of distant metastases, confirmed by PSMA-PET imaging or death due to any cause.
Time frame: Up to approximately 93 months
MFS (standard clinical imaging)
MFS is defined as the time from randomisation until the date of distant metastases, confirmed by standard clinical imaging (CT/MRI and bone scan or PSMA-PET), histology, or death due to any cause.
Time frame: Up to approximately 93 months
Time from randomisation to Progression Free Survival 2 (PFS2)
Time from randomisation to PFS2 is defined as the time from randomisation to the earliest of progression \[defined as radiographic progression, clinical progression, or prostate-specific antigen (PSA) progression\] after initiation of first subsequent systemic treatment following the initial investigator-assessed progression or death. The date of second progression will be investigator assessed according to local standard clinical practice.
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Standard of care ADT will be administered.
Research Site
Phoenix, Arizona, United States
RECRUITINGResearch Site
Tucson, Arizona, United States
NOT_YET_RECRUITINGResearch Site
La Jolla, California, United States
NOT_YET_RECRUITINGResearch Site
La Jolla, California, United States
RECRUITINGResearch Site
Los Angeles, California, United States
RECRUITINGResearch Site
San Diego, California, United States
NOT_YET_RECRUITINGResearch Site
San Luis Obispo, California, United States
NOT_YET_RECRUITINGResearch Site
Lakewood, Colorado, United States
RECRUITINGResearch Site
Jacksonville, Florida, United States
RECRUITINGResearch Site
Tampa, Florida, United States
RECRUITING...and 314 more locations
Time frame: Up to approximately 93 months
Time to biochemical recurrence
Time to biochemical recurrence is defined as the time from randomisation to biochemical recurrence per Phoenix criteria.
Time frame: Up to approximately 93 months
Prostate cancer-specific survival (PCSS)
PCSS is defined as the time from randomisation until the date of death due to the underlying prostate cancer.
Time frame: Up to approximately 11 years
Time to deterioration in urinary symptoms (TTDUS)
TTDUS is defined as the time from randomisation to deterioration in EORTC-QLQ-PR25 (US) subscale scores.
Time frame: Up to approximately 93 months
Time to deterioration in physical function (TTDPF)
TTDPF is defined as the time from randomisation to deterioration in EORTC-QLQ-C30 Physical Function subscale scores.
Time frame: Up to approximately 93 months
Plasma concentrations of saruparib
To assess the PK of saruparib in plasma either with or without abiraterone and explore the relationship between the PK concentration/parameters and selected endpoints (which may include pharmacodynamic parameters, efficacy, and/or safety).
Time frame: Day 1 of Cycle 1, Cycle 3 and Cycle 6 (each cycle is of 28 days)
Area under the curve (AUC)
To assess the PK of saruparib in plasma either with or without abiraterone and explore the relationship between the PK concentration/parameters and selected endpoints (which may include pharmacodynamic parameters, efficacy, and/or safety).
Time frame: Day 1 of Cycle 1, Cycle 3 and Cycle 6 (each cycle is of 28 days)
Maximum observed concentration (Cmax)
To assess the PK of saruparib in plasma either with or without abiraterone and explore the relationship between the PK concentration/parameters and selected endpoints (which may include pharmacodynamic parameters, efficacy, and/or safety).
Time frame: Day 1 of Cycle 1, Cycle 3 and Cycle 6 (each cycle is of 28 days)
Time to Cmax (Tmax)
To assess the PK of saruparib in plasma either with or without abiraterone and explore the relationship between the PK concentration/parameters and selected endpoints (which may include pharmacodynamic parameters, efficacy, and/or safety).
Time frame: Day 1 of Cycle 1, Cycle 3 and Cycle 6 (each cycle is of 28 days)
Number of participants with adverse events (AEs)
To assess the safety and tolerability of saruparib administered in combination with ADT alone (Cohort A) and in combination with ADT + abiraterone (Cohort B).
Time frame: Up to approximately 11 years