Saruparib for Prostate Cancer

(EvoPAR-PR02 Trial)

Recruiting at 100 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Male

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must be taking: Androgen deprivation therapy

Must not be taking: Chemotherapy, Immunotherapy, PARP inhibitors

Disqualifiers: MDS/AML, Bleeding predisposition, Cardiac issues, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 93 months

700 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop using strong inducers and inhibitors of CYP3A4 (a liver enzyme) and certain herbal supplements at least 21 days before starting the study. You also need to avoid drugs that prolong QT interval, which can affect heart rhythm.

What data supports the effectiveness of the drug Saruparib for prostate cancer?

Research on similar drugs, like olaparib, shows that they can help slow down the progression of prostate cancer, especially in patients with specific genetic changes. These drugs, known as PARP inhibitors, have been effective when combined with other treatments, improving outcomes for patients with advanced prostate cancer. ^{1 2 3 4 5}

What makes the drug Saruparib unique for treating prostate cancer?

Saruparib is likely a PARP inhibitor, similar to drugs like olaparib and rucaparib, which target tumors with specific genetic mutations (like BRCA1/2) that affect DNA repair. This approach is different from traditional treatments that focus on androgen receptor signaling, offering a novel option for patients with certain genetic profiles. ^{2 3 6 7 8}

What is the purpose of this trial?

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).

Eligibility Criteria

Men with high-risk, localized or locally advanced prostate cancer who have a BRCA mutation can join this trial. They must be suitable for standard radiation and hormone therapy but cannot participate if they've had previous treatments that could affect the study's results.

Inclusion Criteria

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

Minimum life expectancy of 12 months

I am a man diagnosed with prostate cancer.

Exclusion Criteria

I do not have an active tuberculosis infection.

I have had severe low blood cell counts for more than 2 weeks.

I cannot take pills due to severe nausea, vomiting, gut diseases, or major bowel surgery.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive saruparib or placebo with ADT (+ abiraterone) in a randomized, double-blind manner

93 months

Day 1 of Cycle 1, Cycle 3, and Cycle 6 (each cycle is of 28 days)

Follow-up

Participants are monitored for metastasis-free survival and overall survival

Up to approximately 11 years

Treatment Details

Interventions

• Saruparib

Trial Overview The trial is testing whether adding Saruparib to standard radiation and hormone therapy improves metastasis-free survival compared to a placebo in men with BRCA-mutated prostate cancer.

Participant Groups

Group I: Cohort B: Saruparib (AZD5305) + Physician's Choice ADT + Abiraterone (and prednisone/prednisolone) Experimental Treatment 3 Interventions

Participants will receive saruparib, abiraterone and prednisolone/prednisone along with ADT.

Group II: Cohort A: Saruparib (AZD5305) + Physician's Choice ADT Experimental Treatment 2 Interventions

Participants will receive saruparib along with ADT.

Group III: Cohort A: Placebo + Physician's Choice ADT Placebo Group 2 Interventions

Participants will receive matching placebo to saruparib along with ADT.

Group IV: Cohort B: Placebo + Physician's Choice ADT + Abiraterone (and prednisone/prednisolone) Placebo Group 3 Interventions

Participants will receive matching placebo to saruparib, abiraterone and prednisolone/prednisone along with ADT.

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Parexel

Industry Sponsor

Trials

322

Recruited

137,000+

Peyton Howell

Parexel

Chief Executive Officer

Master of Healthcare Administration from The Ohio State University, Bachelor of Arts in Health Communications from the University of Illinois

Dr. Austin Smith

Parexel

Chief Medical Officer since 2023

MD from the Royal College of Surgeons in Ireland

Findings from Research

In the Phase III PROfound study, olaparib demonstrated improved radiographic progression-free survival (rPFS) and overall survival (OS) compared to control treatments in Asian patients with metastatic castration-resistant prostate cancer, particularly in those with BRCA gene alterations.

The safety profile of olaparib in the Asian subset was consistent with the global population, showing no new safety concerns, indicating it is a well-tolerated treatment option for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib in patients with mCRPC with homologous recombination repair gene alterations: PROfound Asian subset analysis. Matsubara, N., Nishimura, K., Kawakami, S., et al.[2023]

A phase II trial indicates that the combination of the antiandrogen abiraterone and the PARP inhibitor olaparib significantly enhances progression-free survival in patients with metastatic castration-resistant prostate cancer.

This benefit occurs regardless of the patients' homologous recombination repair-mutation status, suggesting a broad applicability of this treatment strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone-Olaparib Combo Aids Men with mCRPC. [2019]

In a phase II trial involving 88 patients with metastatic castration-resistant prostate cancer, danusertib showed minimal efficacy, with only one patient in each treatment group achieving a PSA response after 3 months.

The treatment was generally well tolerated, but neutropenia was a significant side effect, affecting 37.2% of patients in the 6-hour infusion group and 15.8% in the 24-hour infusion group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized phase II study of danusertib in patients with metastatic castration-resistant prostate cancer after docetaxel failure. Meulenbeld, HJ., Bleuse, JP., Vinci, EM., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Olaparib in patients with mCRPC with homologous recombination repair gene alterations: PROfound Asian subset analysis. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Abiraterone-Olaparib Combo Aids Men with mCRPC. [2019]

3. Ireland pubmed.ncbi.nlm.nih.gov

PARPing up the right tree; an overview of PARP inhibitors for metastatic castration-resistant prostate cancer. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Randomized phase II study of danusertib in patients with metastatic castration-resistant prostate cancer after docetaxel failure. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Targeting the {alpha} receptor for platelet-derived growth factor as a primary or combination therapy in a preclinical model of prostate cancer skeletal metastasis. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Rucaparib and olaparib for the treatment of prostate cancer: A clinician's guide to choice of therapy. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Clinical Development of PARP Inhibitors in Treating Metastatic Castration-Resistant Prostate Cancer. [2023]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Rucaparib for the Treatment of Metastatic Castration-resistant Prostate Cancer Associated with a DNA Damage Repair Gene Alteration: Final Results from the Phase 2 TRITON2 Study. [2023]