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

Launched by ASTRAZENECA · Apr 30, 2025

Keywords

ClinConnect Summary

This clinical trial is studying a medication called Saruparib to see if it can help men with high-risk prostate cancer who have a specific gene mutation (BRCA1 or BRCA2). The goal is to find out if adding Saruparib to standard treatments like radiation therapy and hormone therapy can prevent the cancer from spreading to other parts of the body for a longer time compared to a placebo (a substance with no active ingredients). This study is particularly focused on men who have recently been diagnosed with high-risk prostate cancer or have had a recurrence after surgery.

To participate in this trial, men must have a confirmed diagnosis of prostate cancer and a documented BRCA mutation. They should also be in good health overall and have recently undergone radiation therapy with the intent to treat their cancer. Participants will need to undergo some imaging tests to ensure their cancer has not spread before starting the trial. If eligible, they can expect to receive either the Saruparib medication or a placebo as part of their treatment, while continuing their standard prostate cancer therapies. It's important for participants to follow specific guidelines during the trial, such as not fathering children and using protection during sexual activity.

Gender

MALE

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.