Recruiting 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

Phase III Interventional Prostate Cancer

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied: The protocol lists: Saruparib, Placebo, Abiraterone + Prednisolone/Prednisone, Androgen Deprivation Therapy (ADT).
Who it may be relevant to: Registry conditions: Prostate Cancer. Basic parameters: from 18 years · Male.
What needs checking: Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place: United States, Argentina, Australia, Austria, Belgium +23
Next step: Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

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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).

Overview

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).

Interventions

Drug Saruparib
Saruparib will be administered orally.
Drug Placebo
Matching placebo to saruparib will be administered orally.
Drug Abiraterone + Prednisolone/Prednisone
Abiraterone will be administered orally in combination with prednisone/prednisolone.
Drug Androgen Deprivation Therapy (ADT)
Standard of care ADT will be administered.

Primary outcome measures

Metastasis-free survival (MFS) [Time frame: Up to approximately 93 months]

Secondary outcome measures (12)

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)]

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. Participants must be eligible for randomisation within 10 months of initial diagnosis (de novo or BCR). 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 localised 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation: Randomized
Model: Parallel assignment
Masking: Quadruple blind
Primary purpose: Treatment