A Randomised, Double-blind, Placebo-controlled, Phase III Study of Adjuvant Saruparib (AZD5305) in Patients With BRCAm Localised High-Risk Prostate Cancer Receiving Radiotherapy With Androgen Deprivation Therapy (EvoPAR-Prostate02).
Summary
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).
Detailed description
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).
Arms & interventions
- DrugSaruparib
Saruparib will be administered orally.
- DrugPlacebo
Matching placebo to saruparib will be administered orally.
- DrugAbiraterone + Prednisolone/Prednisone
Abiraterone will be administered orally in combination with prednisone/prednisolone.
- DrugAndrogen Deprivation Therapy (ADT)
Standard of care ADT will be administered.
Outcome measures
Primary
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
Secondary
Overall Survival (OS)
Time frame: Up to approximately 11 years
MFS (CT/MRI and bone scan)
Time frame: Up to approximately 93 months
MFS (PSMA-PET)
Time frame: Up to approximately 93 months
MFS (standard clinical imaging)
Time frame: Up to approximately 93 months
Time from randomisation to Progression Free Survival 2 (PFS2)
Time frame: Up to approximately 93 months
Time to biochemical recurrence
Time frame: Up to approximately 93 months
Prostate cancer-specific survival (PCSS)
Time frame: Up to approximately 11 years
Time to deterioration in urinary symptoms (TTDUS)
Time frame: Up to approximately 93 months
Time to deterioration in physical function (TTDPF)
Time frame: Up to approximately 93 months
Plasma concentrations of saruparib
Time frame: Day 1 of Cycle 1, Cycle 3 and Cycle 6 (each cycle is of 28 days)
Area under the curve (AUC)
Time frame: Day 1 of Cycle 1, Cycle 3 and Cycle 6 (each cycle is of 28 days)
Maximum observed concentration (Cmax)
Time frame: Day 1 of Cycle 1, Cycle 3 and Cycle 6 (each cycle is of 28 days)
Time to Cmax (Tmax)
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)
Time frame: Up to approximately 11 years
Eligibility criteria
Study locations (42)
Research Site
Phoenix, Arizona, 85054
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Tucson, Arizona, 85741
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La Jolla, California, 92037
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La Jolla, California, 92093
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Los Angeles, California, 90048
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San Diego, California, 92123
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San Luis Obispo, California, 93401
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Lakewood, Colorado, 80215
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Hialeah, Florida, 33016
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Jacksonville, Florida, 32224
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Tampa, Florida, 33612
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Newnan, Georgia, 30265
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Chicago, Illinois, 60611
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Chicago Ridge, Illinois, 60415
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Greenwood, Indiana, 46143
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Jeffersonville, Indiana, 47130
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Bethesda, Maryland, 20817
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Towson, Maryland, 21204
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Plymouth, Massachusetts, 02360
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Rochester, Minnesota, 55905
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Hackensack, New Jersey, 07601
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Voorhees Township, New Jersey, 08043
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New York, New York, 10065
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Syracuse, New York, 13210
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Columbus, Ohio, 43230
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Springfield, Oregon, 97477
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Hershey, Pennsylvania, 17033
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Lancaster, Pennsylvania, 17601
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Pittsburgh, Pennsylvania, 15212
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Providence, Rhode Island, 02903
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Myrtle Beach, South Carolina, 29572
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Nashville, Tennessee, 37209
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Austin, Texas, 78705
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Austin, Texas, 78745
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Houston, Texas, 77074
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San Antonio, Texas, 78229
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Spring, Texas, 77380
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Salt Lake City, Utah, 84112
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Norfolk, Virginia, 23502
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Roanoke, Virginia, 24014
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Virginia Beach, Virginia, 23462
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Seattle, Washington, 98109