Clinical trial NCT06952803: A Study of Metastases Free Survival With Saruparib vs Placebo Added to a Standard RT/ADT in Men With High-risk Prostate Cancer With a BRCA Mutation
Official title: 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).
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Prostate Cancer
Keywords: Localized/locally advanced prostate cancer
High-risk biochemical recurrence (BCR)
Poly (ADP-ribose) polymerase
Radiation therapy or radiotherapy
Breast cancer gene (BRCA) mutation
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Parexel
First posted: 2025-05-01
Enrollment: 700
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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 localized/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 (localized/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).

Eligibility criteria: Inclusion Criteria:

* Male participants with a histologically documented diagnosis of prostate adenocarcinoma.
* Newly diagnosed high-risk and very high-risk (localised/locally advanced) prostate cancer or a high-risk biochemical recurrence (BCR) following radical prostatectomy.
* Provision of a formalin fixed and paraffin embedded (FFPE) tumour tissue sample.
* Confirmed BRCA1 or BRCA2 mutation status by central tumour tissue is required for enrolment.
* Participants required to have a computed tomography (CT) or magnetic resonance imaging (MRI) and a bone scan following the completion of their planned RT. This screening scan must confirm no evidence of disease or evidence of disease confined to the pelvis (M0).
* Participants required to have a prostate-specific membrane antigen-positron emission tomography (PSMA-PET) following the completion of their planned RT. This screening scan must confirm no evidence of disease or evidence of disease confined to the pelvis (M0).
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 with no deterioration over the 2 weeks prior to randomization.
* Minimum life expectancy of 12 months.
* Adequate organ and bone marrow function as described in study protocol.
* All participants will have received either primary or salvage RT. Radiotherapy administered to the prostate (± pelvis) either in the primary or salvage setting must be delivered with curative intent. Use of metastases-directed therapy, as part of the RT radiation plan, is permitted as localized RT treatment for a metastatic lesion(s) outside the pelvis.
* All participants will have received a planned regimen of ADT with a gonadotropin releasing hormone (GnRH) analogue.
* Participants must not father children or donate sperm from signing informed consent form (ICF), during the study intervention and for 6 months after the last dose of study intervention.
* Participants must use a condom (with spermicide - where permitted) from signing ICF, during study intervention, and for 6 months after the last dose of study drug, with all sexual partners.

Exclusion Criteria:

* Participants with a history of myelodysplastic syndrome (MDS)/ acute myeloid leukemia (AML) or with features suggestive of MDS/AML.
* Participants with any known predisposition to bleeding \[e.g., active peptic ulceration, recent (within 6 months) hemorrhagic stroke, proliferative diabetic retinopathy\].
* Any history of persisting (\> 2 weeks) severe cytopenia due to any cause.
* Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of saruparib and/or abiraterone.
* History of another primary malignancy, with exceptions.
* Persistent toxicities \[Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥ 2\] caused by previous anticancer therapy.
* Cardiac criteria, including history of arrhythmia and cardiovascular disease.
* Evidence of active and uncontrolled hepatitis B and/or hepatitis C.
* Evidence of active and uncontrolled human immunodeficiency virus (HIV) infection.
* Active tuberculosis infection.
* Any prior chemotherapy (i.e., docetaxel) or immunotherapy; any prior treatment with a poly (ADP-ribose) polymerase (PARP) inhibitor.
* Prior treatment within 14 days with blood product support or growth factor support.
* Concomitant use of strong inducers and inhibitors of CYP3A4 (applies to saruparib and abiraterone) or herbal supplements within 21 days or at least 5 half-lives (whichever is longer), of randomization.
* Concomitant use of drugs that are known to prolong QT and have a known risk of Torsades de Pointes (TdP).
* Participants with a known hypersensitivity to saruparib or any excipients of these products.

Primary outcomes:
measure: Metastasis-free survival (MFS)
timeFrame: Up to approximately 93 months
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: Up to approximately 11 years
measure: MFS (CT/MRI and bone scan)
timeFrame: Up to approximately 93 months
measure: MFS (PSMA-PET)
timeFrame: Up to approximately 93 months
measure: MFS (standard clinical imaging)
timeFrame: Up to approximately 93 months
measure: Time from randomisation to Progression Free Survival 2 (PFS2)
timeFrame: Up to approximately 93 months
measure: Time to PSA progression
timeFrame: Up to approximately 93 months
measure: Prostate cancer-specific survival (PCSS)
timeFrame: Up to approximately 11 years
measure: Time to deterioration in urinary symptoms (TTDUS)
timeFrame: Up to approximately 93 months
measure: Time to deterioration in physical function (TTDPF)
timeFrame: Up to approximately 93 months
measure: Plasma concentrations of saruparib
timeFrame: Day 1 of Cycle 1, Cycle 3 and Cycle 6 (each cycle is of 28 days)
measure: Area under the curve (AUC)
timeFrame: Day 1 of Cycle 1, Cycle 3 and Cycle 6 (each cycle is of 28 days)
measure: Maximum observed concentration (Cmax)
timeFrame: Day 1 of Cycle 1, Cycle 3 and Cycle 6 (each cycle is of 28 days)
measure: Time to Cmax (Tmax)
timeFrame: Day 1 of Cycle 1, Cycle 3 and Cycle 6 (each cycle is of 28 days)
measure: Number of participants with adverse events (AEs)
timeFrame: Up to approximately 11 years
Other outcomes:
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Study officials:
References: