Clinical Study to Assess the Efficacy and Safety of Olaparib in Chinese Patients With Metastatic Castration-Resistant Prostate Cancer Who Have Failed Prior Treatment With a New Hormonal Agent and Have BRCA1/2 Mutations

A Randomized, Open-label Study to Assess the Efficacy and Safety of Olaparib Versus Enzalutamide or Abiraterone Acetate in Chinese Men With Metastatic Castration-Resistant Prostate Cancer Who Have Failed Prior Treatment With a New Hormonal Agent and Have BRCA1/2 Mutations (PROfound-CN)

The purpose of this study is to evaluate the efficacy and safety of Olaparib compared with standard of care (Enzalutamide or Abiraterone Acetate) in Chinese men with metastatic castration-resistant prostate cancer who have failed prior treatment with a new hormonal agent and have BRCA1/2 mutations.

Study Overview

• Status: Active, not recruiting
• Conditions: Metastatic Castration-resistant Prostate Cancer
• Intervention / Treatment: Drug: olaparib; Drug: enzalutamide; Drug: abiraterone acetate; Drug: Prednisone

Detailed Description

This is a Phase IV, randomized, open-label, 2-arm, multicenter study evaluating the efficacy and safety of olaparib in Chinese men with metastatic castration-resistant prostate cancer (mCRPC) who have failed prior treatment with a new hormonal agent (NHA) and have BRCA1/2 mutations. Approximately 42 subjects will be randomized in a 2:1 ratio to olaparib or to investigator's choice of NHA (enzalutamide or abiraterone acetate).

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100050
    • Research Site
  • Bengbu, China, 233004
    • Research Site
  • Changsha, China, 410013
    • Research Site
  • Changsha, China, 410008
    • Research Site
  • Chengdu, China, 610000
    • Research Site
  • Chongqing, China, 408099
    • Research Site
  • Fuzhou, China, 350005
    • Research Site
  • Guangzhou, China, 510180
    • Research Site
  • Guangzhou, China, 510060
    • Research Site
  • Hangzhou, China, 310003
    • Research Site
  • Hangzhou, China, 310009
    • Research Site
  • Hangzhou, China, 310014
    • Research Site
  • Hefei, China, 230601
    • Research Site
  • Jiaxing, China, 314001
    • Research Site
  • Jinan, China, 250012
    • Research Site
  • Jinan, China, 250021
    • Research Site
  • Jining, China, 272029
    • Research Site
  • Kunming, China, 650101
    • Research Site
  • Lanzhou, China, 730030
    • Research Site
  • Linyi, China, 276000
    • Research Site
  • Nanchang, China, 330006
    • Research Site
  • Nantong, China, 226361
    • Research Site
  • Ningbo, China, 315010
    • Research Site
  • Shanghai, China, 200032
    • Research Site
  • Shanghai, China, 200002
    • Research Site
  • Shenyang, China, 110004
    • Research Site
  • Suzhou, China, 215004
    • Research Site
  • Taiyuan, China, 030000
    • Research Site
  • Tianjin, China, 300060
    • Research Site
  • Wanzhou, China, 404000
    • Research Site
  • Wuhan, China, 430022
    • Research Site
  • Wuxi, China, 214002
    • Research Site
  • Wuxi, China, 214023
    • Research Site
  • Xi'an, China, 710077
    • Research Site
  • Zhengzhou, China, 450052
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria：

1. Histologically confirmed diagnosis of prostate cancer.
2. Documented evidence of metastatic castration resistant prostate cancer (mCRPC).
3. Subjects must have progressed on prior new hormonal agent (e.g. abiraterone acetate and/or enzalutamide) for the treatment of metastatic prostate cancer and/or CRPC .
4. Ongoing therapy with LHRH analog or bilateral orchiectomy.
5. Radiological progression at study entry while on androgen deprivation therapy (or after bilateral orchiectomy).
6. Deleterious or suspected deleterious BRCA1/2 mutation in tumor tissue.
7. Normal organ and bone marrow function measured within 28 days prior to administration of study treatment.
8. Eastern Cooperative Oncology Group (ECOG) performance status 0-2 with no deterioration over the previous 2 weeks prior to baseline or day of first dosing.

Exclusion criteria：

1. Any previous treatment with a poly (adenosine diphosphate [ADP] ribose) polymerase (PARP) inhibitor, including olaparib.
2. Subjects who had any previous treatment with DNA-damaging cytotoxic chemotherapy, except if for non-prostate cancer indication and last dose > 5 years prior to randomization.
3. History of another primary malignancy except for malignancy treated with curative intent with no known active disease for ≥5 years before the first dose of study intervention and of low potential risk for recurrence.
4. Spinal cord compression or brain metastases unless asymptomatic, stable, and not requiring steroids for at least 4 weeks prior to start of study intervention.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Olaparib; Olaparib is available as a film-coated tablet containing 150 mg or 100 mg of olaparib. Subjects will be administered study treatment orally at a dose of 300 mg twice daily (bid). The planned dose of 300 mg bid will be made up of two x 150 mg tablets twice daily, with 100 mg tablets used to manage dose reductions	Drug: olaparib; 300 mg (2x 150 mg tablets) twice daily; Other Names: Lynparza
Active Comparator: Enzalutamide OR abiraterone acetate; Enzalutamide: Enzalutamide is available as capsules or tablets containing 40 mg of enzalutamide. Subjects will be administered study treatment orally at a dose of 160 mg once daily. Abiraterone acetate with prednisone: Abiraterone acetate is available as tablets containing 250 mg of abiraterone acetate. Subjects will be administered study treatment orally at a dose of 1,000 mg once daily. Prednisone is 5mg twice daily. Prednisolone is permitted for use instead of prednisone if necessary.	Drug: enzalutamide; 160 mg (4 x 40 mg capsules) once daily; Other Names: XTANDI; Drug: abiraterone acetate; 1,000 mg (4 x 250 mg tablets) once daily; Other Names: ZYTIGA; Drug: Prednisone; 5mg(5mg x 1 tablet) twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiological Progression-free Survival - Based on Blinded Independent Central Review (BICR)	rPFS is defined as the time from randomization until the date of objective disease progression (soft tissue or bone) or death (by any cause in the absence of progression) regardless of whether the patient withdraws from randomized therapy or receives another anti-cancer therapy prior to progression.	Tumor assessments every 8 weeks (± 1 week) relative to the date of randomization until radiological progression as assessed by BICR or death (median duration of treatment of 9 and 6 months for Olaparib and Investigators Choice of NHA respectively).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Confirmed Objective Response Rate (ORR), Based on Blinded Independent Review (BICR)	Confirmed ORR is the percentage of patients with a Complete response (CR) or Partial response (PR), in their soft tissue disease per (RECIST v1.1), in the absence of progression on bone scan per Prostate Cancer Working Group 3 (PCWG3), confirmed >=4 weeks later. Per RECIST v1.1, CR=Disappearance of all target lesions; PR = >=30% decrease in the sum of diameters of target lesions. For each treatment group, confirmed ORR is the number of patients with a confirmed CR or PR divided by the number of patients in the treatment group.	Tumor assessments every 8 weeks (± 1 week) from randomisation until radiographic progression assessed by BICR (median duration of treatment of 9 and 6 months for Olaparib and Investigators Choice of NHA respectively).
Overall Survival	OS is the time from the date of randomization until death due to any cause.	From the time from the date of randomization until death due to any cause. Assessments continue up to 27 months after the first patient was randomized.
Time to First Symptomatic Skeletal-related Event	Time from first dose to the first symptomatic skeletal-related event	Time from randomization to the first SSRE-radiation for skeletal symptoms, confirmed pathological fracture, confirmed spinal cord compression, or orthopaedic surgery for bone metastases. Assessments continue up to 27 months post first patient enrolled.
Time to Opiate Use for Cancer-related Pain	Time from randomization to opiate use for cancer-related pain	Opioid use will be recorded at baseline and at every study visit, including the safety follow-up visit. Assessments continue up to 27 months post first patient enrolled.
Prostate-specific Antigen Response	Proportion of participants achieving a ≥50% decrease in PSA from baseline to the lowest post-baseline PSA result, confirmed by a second consecutive PSA assessment at least 3 weeks later (PSA50 response)	Blood samples for PSA assessment will be collected at baseline and every 4 weeks throughout the treatment phase, including at the study treatment discontinuation visit. Assessments continue up to 27 months post first patient enrolled.
Prostate-specific Antigen Response	Best percentage change from baseline in PSA is defined as the biggest reduction in PSA level compared with baseline (or the smallest increase in the absence of a reduction) taking account of all PSA values collected for each patient.	Blood samples for PSA assessment will be collected at baseline and every 4 weeks throughout the treatment phase, including at the study treatment discontinuation visit. Assessments continue up to 27 months post first patient enrolled.
Time From Randomization to Second Progression or Death	Time from randomization to second progression by investigator assessment of radiological or clinical progression or death (PFS2)	Tumor assessments will be performed every 8 weeks (±7 days) after randomization until radiologic progression or death, unless the participant withdraws consent. Assessments continue up to 27 months post first patient enrolled.
Subsequent Anticancer Therapy		Recorded from post discontinuation of study treatment up to primary data cut off date. Assessments continue up to 27 months post first patient enrolled.

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Merck Sharp & Dohme LLC; Foundation Medicine; Myriad Genetics, Inc.
• Investigators: Principal Investigator: Fangjian Zhou, M.D., Sun Yat-sen University Cancer Center

Publications and helpful links

Helpful Links

• Redacted CSP
• Redacted SAP
• Redacted CSR synopsis

Study record dates

Study Major Dates

• Study Start (Actual): July 29, 2022
• Primary Completion (Actual): October 22, 2024
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: July 11, 2022
• First Submitted That Met QC Criteria: July 11, 2022
• First Posted (Actual): July 13, 2022

Study Record Updates

• Last Update Posted (Actual): April 21, 2026
• Last Update Submitted That Met QC Criteria: March 31, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: metastatic castration-resistant prostate cancer (mCRPC); BRCA1/2 mutations
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms; Polycyclic Compounds; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Pregnadienediols; Androstenes; Androstanes; Abiraterone Acetate; Prednisone; enzalutamide; olaparib
• Other Study ID Numbers: D081LC00002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment（https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure).

"Yes" indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved, AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access.For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No