Study on Olaparib Plus Abiraterone as First-line Therapy in Men With Metastatic Castration-resistant Prostate Cancer (China Cohort)

NCT05171816 | Active Not Recruiting Phase 3 Results DMC FDA Drug

• 1 other identifier: D081SC00001Sub
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 26

Brief Summary

The purpose of this study is to evaluate the efficacy and safety (including evaluating side effects) of combination of olaparib and abiraterone versus placebo and abiraterone in patients with metastatic castration-resistant prostate cancer (mCRPC) who have received no prior cytotoxic chemotherapy or new hormonal agents (NHAs) at metastatic castration-resistant prostate cancer (mCRPC) stage.

Conditions

Metastatic Castration-resistant Prostate Cancer

Keywords

metastatic castration-resistant prostate cancer (mCRPC)

Outcome Measures

Primary Outcomes (1)

• Radiological Progression Free Survival (rPFS)

  Radiological progression free survival is defined as the time from randomisation until the earlier date of radiological progression or death (by any cause in the absence of progression), regardless of whether the patient withdraws from randomised therapy or receives another anticancer therapy prior to progression. Per RECIST v1.1, progression is defined as the sum of TLs has a 20% and absolute ≥ 5mm increase from nadir, and/or unequivocal progression in any non target lesions, and/or any new lesion identified. Per PCWG3, progression on a bone scan is defined as 2 or more new lesions observed from the first visit after baseline compared to baseline, or from all other visits compared to first visit after baseline. A confirmatory scan is required.

  Tumour imaging CT/MRI and bone scan were assessed every 8 weeks from randomisation to week 24 and then every 12 weeks until RECIST progression. Patients were followed up for 479 days (approx 16 months) at minimum and 913 days (approx 30 months) at maximum

Secondary Outcomes (8)

• Overall Survival (OS)

  Assessed every 12 weeks from randomisation until death or data cut-off. The endpoint was followed up for 479 days (approx 16 months) at minimum and 913 days (approx 30 months) at maximum.

• Time to First Subsequent Anticancer Therapy or Death (TFST)

  Assessed from from randomization on 30 day follow-up after last dose of study medication and every 12 weeks after that until DCO. The endpoint was followed up for 479 days (approx 16 months) at minimum and 913 days (approx 30 months) at maximum.

• Time to Pain Progression (TTPP)

  The BPI-SF and AQA were assessed on screening, day 1, day 15, day 29, day 43, day 57, day 71, and every 4 weeks after week 13 until DCO. The endpoint was followed up for 479 days (approx 16 months) at minimum and 913 days (approx 30 months) at maximum.

• Time to Opiate Use

  Assessed on screening, days 1, 29, and 57, every 4 weeks after week 13, treatment discontinuation, and 30-day follow-up after last dose of study medication. Followed up for 479 days (approx 16 months) at minimum and 913 days (approx 30 months) at maximum.

• Time to a Symptomatic Skeletal-Related Event (SSRE)

  Assessed at every visit from randomisation up to and including treatment discontinuation visit. The endpoint was followed up for 479 days (approx 16 months) at minimum and 913 days (approx 30 months) at maximum.

Study Arms (2)

olaparib plus abiraterone

EXPERIMENTAL

Olaparib is available as a film-coated tablet containing 100 milligrams (mg) or 150 milligrams (mg) of olaparib. Subjects will be administered olaparib orally at a dose of 300 milligrams (mg) twice daily (bid). The initial dosage of 300 milligrams (mg) twice daily will be composed of 2 x 150 milligrams (mg) tablets per dose. The 100 milligrams (mg) and 150 milligrams (mg) tablets will be used to manage dose reductions during the study. Abiraterone acetate with prednisone or prednisolone will be sourced locally as commercially available materials. Subjects will be administered abiraterone orally at a dose of 1000 milligrams (mg) once daily, in combination with prednisone or prednisolone 5 milligrams (mg) administered orally twice daily.

Drug: olaparib; Drug: abiraterone acetate

placebo plus abiraterone

PLACEBO COMPARATOR

Placebo to match olaparib is available as a film-coated tablet in 100 milligrams (mg) or 150 milligrams (mg). Subjects will be administered placebo orally at a dose of 300 milligrams (mg) twice daily (bid). The initial dosage of 300 milligrams (mg) twice daily will be composed of 2 x 150 milligrams (mg) tablets per dose. The 100 milligrams (mg) and 150 milligrams (mg) tablets will be used to manage dose reductions during the study. Abiraterone acetate with prednisone or prednisolone will be sourced locally as commercially available materials. Subjects will be administered abiraterone orally at a dose of 1000 milligrams (mg) once daily, in combination with prednisone or prednisolone 5 milligrams (mg) administered orally twice daily.

Drug: abiraterone acetate

Interventions

olaparib DRUG

300 mg (2 x 150 milligrams (mg) tablets) twice daily

Also known as: Lynparza

olaparib plus abiraterone

abiraterone acetate DRUG

1000 milligrams (mg) once daily

Also known as: Zytiga

olaparib plus abiraterone; placebo plus abiraterone

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form and in the study protocol.
• Provision of signed and dated, written informed consent form prior to any mandatory study specific procedures, sampling, and analyses.
• Provision of informed consent for genetic research prior to collection of sample.
• Provision of informed consent for biomarker research prior to collection of sample.
• If a patient declines to participate in the optional exploratory genetic research or the optional biomarker research, there will be no penalty or loss of benefit to the patient. The patient will not be excluded from other aspects of the study.
• Patients must be ≥18 years of age (or ≥19 years of age in South Korea) at the time of signing the informed consent form. For patients enrolled in Japan who are \<20 years of age, written informed consent should be obtained from the patient and from his legally acceptable representative.
• Histologically or cytologically confirmed prostate adenocarcinoma.
• Metastatic status defined as at least 1 documented metastatic lesion on either a bone scan or a computed tomography(CT)/ magnetic resonance imaging (MRI) scan.
• First-line metastatic castration-resistant prostate cancer (mCRPC).
• Ongoing androgen deprivation with gonadotropin-releasing hormone analogue or bilateral orchiectomy, with serum testosterone \<50 nanograms per decilitre (ng/dL) (\<2.0 nanomoles per litre (nmol/L)) within 28 days before randomisation. Patients receiving androgen deprivation therapy (ADT) at study entry should continue to do so throughout the study.
• Candidate for abiraterone therapy with documented evidence of progressive disease.
• Patients must have normal organ and bone marrow function measured within 28 days prior to administration of study treatment.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1, with no deterioration over the previous 2 weeks.
• The participant has, in the opinion of the investigator, a life expectancy of at least 6 months.
• Prior to randomisation, sites must confirm availability of either an archival formalin fixed, paraffin embedded (FFPE) tumour tissue sample, or a new biopsy taken during the screening window, which meets the minimum pathology and sample requirements in order to enable homologous recombination repair (HRR) status subgroup analysis of the primary endpoint radiographic progression-free survival (rPFS). If there is not written confirmation of the availability of tumour tissue prior to randomisation, the patient is not eligible for the study.

You may not qualify if:

• Has a known additional malignancy that has had progression or has required active treatment in the last 5 years.
• Patients with myelodysplastic syndrome (MDS)/ acute myeloid leukaemia (AML) or with features suggestive of yelodysplastic syndrome (MDS)/ acute myeloid leukaemia (AML).
• Clinically significant cardiovascular disease Association Class II-IV heart failure or cardiac ejection fraction measurement of \<50% during screening as assessed by echocardiography or multigated acquisition scan.
• Planned or scheduled cardiac surgery or percutaneous coronary intervention procedure.
• Prior revascularisation procedure (significant coronary, carotid, or peripheral artery stenosis).
• Uncontrolled hypertension (systolic blood pressure (BP) ≥160 millimeters of mercury (mmHg) or diastolic blood pressure (BP) ≥95 millimeters of mercury (mmHg)).
• History of uncontrolled pituitary or adrenal dysfunction.
• Active infection or other medical condition that would make prednisone/prednisolone use contraindicated.
• Any chronic medical condition requiring a systemic dose of corticosteroid \>10 milligrams (mg) prednisone/prednisolone per day.
• Patients who are considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection.
• Persistent toxicities (Common Terminology Criteria for Adverse Events \[CTCAEs\] grade \>2) caused by previous cancer therapy, excluding alopecia.
• Patients with brain metastases. A scan to confirm the absence of brain metastases is not required.
• Patients with spinal cord compression are excluded unless they are considered to have received definitive treatment for this and have evidence of clinically stable disease for 4 weeks.
• Patients who are unevaluable for both bone and soft tissue progression
• Patients who are unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication.

Sponsors & Collaborators

• AstraZeneca: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (26)

Research Site

Beijing, 100034, China

Location

Research Site

Beijing, 100050, China

Location

Research Site

Beijing, 100142, China

Location

Research Site

Beijing, 100191, China

Location

Research Site

Beijing, 100730, China

Location

Research Site

Chongqing, 400038, China

Location

Research Site

Guangzhou, 510180, China

Location

Research Site

Guangzhou, 510515, China

Location

Research Site

Guizhou, 550002, China

Location

Research Site

Henan, 450008, China

Location

Research Site

Hubei, 430030, China

Location

Research Site

Hunan, 410008, China

Location

Research Site

Hunan, 410013, China

Location

Research Site

Jilin, 130012, China

Location

Research Site

Jilin, 130021, China

Location

Research Site

Liaoning, 110001, China

Location

Research Site

Nanchang, 330006, China

Location

Research Site

Nanjing, 2100008, China

Location

Research Site

Ningbo, 315000, China

Location

Research Site

Shanghai, 200032, China

Location

Research Site

Shanghai, 200040, China

Location

Research Site

Sichuan, 610041, China

Location

Research Site

Sichuan, 610072, China

Location

Research Site

Xi'an, 710061, China

Location

Research Site

Zhejiang, 310009, China

Location

Research Site

Zhejiang, 310014, China

Location

MeSH Terms

Interventions

olaparib; Abiraterone Acetate

Intervention Hierarchy (Ancestors)

Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Limitations and Caveats

The study treatment period overlapped with the COVID-19 global pandemic caused by SARS-CoV-2 and declared by the World Health Organization on 11 March 2020. 55 patients had a visit impacted by the COVID-19 pandemic.

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca

information.center@astrazeneca.com

1-877-240-9479

Study Officials

• Noel Clarke, M.D.

  Christie Hospital Foundation Trust

  PRINCIPAL INVESTIGATOR

• Fred Saad, MD

  University of Montreal Hospital Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2021
• First Posted: December 29, 2021
• Study Start: June 24, 2021
• Primary Completion: January 22, 2024
• Study Completion: April 28, 2026
• Last Updated: March 11, 2026
• Results First Posted: June 29, 2025

Record last verified: 2026-02

Locations

CN (26)