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

NCT03732820 | Active Not Recruiting Phase 3 Results DMC FDA Drug

• 2 other identifiers: D081SC000012018-002011-10
• Study Type: interventional
• Target: 895
• Locations: 17 countries
• Sites: 132

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)

• Number of Participants With Radiological Progression Free Survival (rPFS) Event by Investigator Assessment

  An rPFS event is defined as progression determined by Response Evaluation Criteria in Solid Tumours version 1.1 \[RECIST 1.1\] and/or Prostate Cancer Working Group 3 \[PCWG-3\] 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.

  Assessed from date of randomisation to data cut off (DCO1): 30Jul2021 (Approx. 2 years 9 months)

Secondary Outcomes (8)

• Number of Participants With Overall Survival (OS) Event

  Assessed from date of randomisation to data cut off (DCO3): 12Oct2022 (Approx. 3 years 11 months). DCO3 is the final data cut-off for the OS analysis and therefore no further updates will be made.

• Number of Participants With Time to First Subsequent Anticancer Therapy or Death (TFST) Event

  Assessed from date of randomisation to data cut off (DCO3): 12Oct2022 (Approx. 3 years 11 months)

• Number of Participants With Time to Pain Progression (TTPP) Event

  Assessed from date of randomisation to data cut off (DCO3): 12Oct2022 (Approx. 3 years 11 months)

• Number of Participants With Opiate Use

  Assessed from date of randomisation to data cut off (DCO3): 12Oct2022 (Approx. 3 years 11 months)

• Number of Participants With First Symptomatic Skeletal Related Event (SSRE)

  Assessed from date of randomisation to data cut off (DCO3): 12Oct2022 (Approx. 3 years 11 months)

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 (132)

Research Site

Birmingham, Alabama, 35209, United States

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Anchorage, Alaska, 99503, United States

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Tucson, Arizona, 85704, United States

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Tucson, Arizona, 85741, United States

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Clovis, California, 93611, United States

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Los Angeles, California, 90027, United States

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Los Angeles, California, 90073, United States

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Sacramento, California, 95817, United States

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San Diego, California, 92123, United States

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Denver, Colorado, 80211, United States

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Lisle, Illinois, 60532, United States

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Jeffersonville, Indiana, 47130, United States

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New Orleans, Louisiana, 70112, United States

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Detroit, Michigan, 48202, United States

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Grand Rapids, Michigan, 49503, United States

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St Louis, Missouri, 63106, United States

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Bozeman, Montana, 59715, United States

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Omaha, Nebraska, 68130, United States

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Paramus, New Jersey, 07652, United States

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Brooklyn, New York, 11220, United States

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New Hyde Park, New York, 11042, United States

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Rochester, New York, 14642, United States

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Syracuse, New York, 13210, United States

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Durham, North Carolina, 27710, United States

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Philadelphia, Pennsylvania, 19111, United States

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Charleston, South Carolina, 29425, United States

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Myrtle Beach, South Carolina, 29572, United States

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Milwaukee, Wisconsin, 53226, United States

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Box Hill, 3128, Australia

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Darlinghurst, 2010, Australia

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Greenslopes, 4120, Australia

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Herston, 4029, Australia

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Kingswood, 2747, Australia

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Kurralta Park, 5037, Australia

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St Albans, 3021, Australia

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Waratah, 2298, Australia

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Ghent, 9000, Belgium

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Belo Horizonte, 30110-022, Brazil

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Curitiba, 80810-050, Brazil

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Fortaleza, 60336-232, Brazil

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Porto Alegre, 91350-200, Brazil

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Rio de Janeiro, 22793-080, Brazil

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São José do Rio Preto, 15090-000, Brazil

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São Paulo, 01221-020, Brazil

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São Paulo, 04266-010, Brazil

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Calgary, Alberta, T2V 1P9, Canada

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Edmonton, Alberta, T6G 1Z2, Canada

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Kelowna, British Columbia, V1Y 5L3, Canada

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Halifax, Nova Scotia, B3H 1V7, Canada

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London, Ontario, N6A 5W9, Canada

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Toronto, Ontario, M4N 3M5, Canada

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Toronto, Ontario, M5G 2M9, Canada

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Greenfield Park, Quebec, J4V 2H1, Canada

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Montreal, Quebec, H2X 3E4, Canada

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Montreal, Quebec, H3T 1E2, Canada

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Santiago, 7500787, Chile

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Santiago, 7520349, Chile

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Temuco, 4781156, Chile

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Viña del Mar, 2540488, Chile

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Brno, 656 53, Czechia

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Prague, 120 00, Czechia

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Prague, 140 59, Czechia

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Prague, 150 06, Czechia

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Angers, 49033, France

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Besançon, 25030, France

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Caen, 14076, France

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Pierre-Bénite, 69495, France

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Quimper, 29107, France

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Vandœuvre-lès-Nancy, 54519, France

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Bergisch Gladbach, 51465, Germany

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Bremen, 28277, Germany

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Cologne, 50968, Germany

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Duisburg, 47169, Germany

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Freiburg im Breisgau, 79106, Germany

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Heinsberg, 52525, Germany

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Mettmann, 40822, Germany

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Nuremberg, 90419, Germany

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Nürtingen, 72622, Germany

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Ulm, 89081, Germany

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Milan, 20133, Italy

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Milan, 20141, Italy

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Naples, 80131, Italy

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Orbassano, 10043, Italy

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Pavia, 27100, Italy

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Bunkyō City, 113-8431, Japan

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Hirakata-shi, 573-1191, Japan

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Kanazawa, 920-8641, Japan

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Kashihara-shi, 634-8522, Japan

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Kawagoe-shi, 350-8550, Japan

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Kita-gun, 761-0793, Japan

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Kyoto, 606-8507, Japan

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Maebashi, 371-8811, Japan

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Miyazaki, 889-1692, Japan

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Nagoya, 466-8560, Japan

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Osaka, 541-8567, Japan

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Osaka, 545-8586, Japan

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Osakasayama-shi, 589-8511, Japan

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Sagamihara-shi, 252-0375, Japan

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Sakura-shi, 285-8741, Japan

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Shinjuku-ku, 160-8582, Japan

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Toon-shi, 791-0295, Japan

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Yokohama, 232-0024, Japan

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Hilversum, 1213 XZ, Netherlands

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Nijmegen, 6525 GA, Netherlands

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Tilburg, 5042 AD, Netherlands

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Bratislava, 851 05, Slovakia

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Prešov, 08001, Slovakia

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Šaľa, 92701, Slovakia

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Trenčín, 911 01, Slovakia

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Daegu, 41404, South Korea

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Goyang-si, 10408, South Korea

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Seoul, 03080, South Korea

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Seoul, 03722, South Korea

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Seoul, 05505, South Korea

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Seoul, 06591, South Korea

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Barcelona, 08036, Spain

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Girona, 17007, Spain

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Madrid, 08035, Spain

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Madrid, 28041, Spain

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Málaga, 29010, Spain

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Seville, 41009, Spain

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Adana, 01060, Turkey (Türkiye)

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Ankara, 06590, Turkey (Türkiye)

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Ankara, 06800, Turkey (Türkiye)

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Cordaleo, 35575, Turkey (Türkiye)

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Istanbul, 34030, Turkey (Türkiye)

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Izmir, 35360, Turkey (Türkiye)

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Guildford, GU2 7WG, United Kingdom

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Manchester, M20 4BX, United Kingdom

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Sheffield, S10 2SJ, United Kingdom

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Southampton, SO16 6YD, United Kingdom

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Swansea, SA2 8QA, United Kingdom

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Related Publications (6)

• Armstrong AJ, Saad F, Oya M, Vianna K, Ozguroglu M, Gedye C, Buchschacher GL Jr, Lee JY, Emmenegger U, Navratil J, Virizuela JA, Salazar A, Maillet D, Uemura H, Hosius C, McGuinness D, Degboe A, Clarke N. Patient-reported Outcomes for Men with Metastatic Castration-resistant Prostate Cancer Who Received Olaparib plus Abiraterone Versus Placebo plus Abiraterone in the Phase 3 PROpel Study. Eur Urol Oncol. 2026 Feb;9(1):80-92. doi: 10.1016/j.euo.2025.09.010. Epub 2025 Nov 17.

  PMID: 41253648 DERIVED

• Oya M, Joung JY, Lee JY, Sugimoto M, Choi YD, Hong JH, Uemura H, Nishimura K, Tsumura H, Kawakami S, Hirayama Y, Kwon TG, Kwak C, Suzuki H, Fujita T, Nii M, McGuinness D, Dujka M, Poehlein C, Saad F, Clarke N. Olaparib Plus Abiraterone in Asian Patients With Metastatic Castration-Resistant Prostate Cancer: PROpel Subset Analysis. Cancer Sci. 2025 Jun;116(6):1638-1647. doi: 10.1111/cas.16459. Epub 2025 Mar 18.

  PMID: 40099663 DERIVED

• Heiss BL, Chang E, Gao X, Truong T, Brave MH, Bloomquist E, Shah A, Hamed S, Kraft J, Chiu HJ, Ricks TK, Tilley A, Pierce WF, Tang L, Abukhdeir A, Kalavar S, Philip R, Tang S, Pazdur R, Amiri-Kordestani L, Kluetz PG, Suzman DL. US Food and Drug Administration Approval Summary: Talazoparib in Combination With Enzalutamide for Treatment of Patients With Homologous Recombination Repair Gene-Mutated Metastatic Castration-Resistant Prostate Cancer. J Clin Oncol. 2024 May 20;42(15):1851-1860. doi: 10.1200/JCO.23.02182. Epub 2024 Mar 7.

  PMID: 38452327 DERIVED

• Clarke NW, Armstrong AJ, Thiery-Vuillemin A, Oya M, Shore N, Loredo E, Procopio G, de Menezes J, Girotto G, Arslan C, Mehra N, Parnis F, Brown E, Schlurmann F, Joung JY, Sugimoto M, Virizuela JA, Emmenegger U, Navratil J, Buchschacher GL, Poehlein C, Harrington EA, Desai C, Kang J, Saad F. Abiraterone and Olaparib for Metastatic Castration-Resistant Prostate Cancer. NEJM Evid. 2022 Sep;1(9):EVIDoa2200043. doi: 10.1056/EVIDoa2200043. Epub 2022 Jun 3.

  PMID: 38319800 DERIVED

• Fallah J, Xu J, Weinstock C, Brave MH, Bloomquist E, Fiero MH, Schaefer T, Pathak A, Abukhdeir A, Bhatnagar V, Chiu HJ, Ricks T, John C, Hamed S, Lee C, Pierce WF, Kalavar S, Philip R, Tang S, Amiri-Kordestani L, Pazdur R, Kluetz PG, Suzman D. FDA Approval Summary: Olaparib in Combination With Abiraterone for Treatment of Patients With BRCA-Mutated Metastatic Castration-Resistant Prostate Cancer. J Clin Oncol. 2024 Feb 10;42(5):605-613. doi: 10.1200/JCO.23.01868. Epub 2023 Dec 21.

  PMID: 38127780 DERIVED

• Saad F, Clarke NW, Oya M, Shore N, Procopio G, Guedes JD, Arslan C, Mehra N, Parnis F, Brown E, Schlurmann F, Joung JY, Sugimoto M, Sartor O, Liu YZ, Poehlein C, Barker L, Del Rosario PM, Armstrong AJ. Olaparib plus abiraterone versus placebo plus abiraterone in metastatic castration-resistant prostate cancer (PROpel): final prespecified overall survival results of a randomised, double-blind, phase 3 trial. Lancet Oncol. 2023 Oct;24(10):1094-1108. doi: 10.1016/S1470-2045(23)00382-0. Epub 2023 Sep 12.

  PMID: 37714168 DERIVED

Related Links

• Redacted CSR synopsis
• Redacted SAP
• csp\_final\_compressed
• CSR Addendum 1
• CSR addendum 2 - synopsis

MeSH Terms

Interventions

olaparib; Abiraterone Acetate

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca

information.center@astrazeneca.com

1-877-240-9479

Study Officials

• Fred Saad, MD

  University of Montreal Hospital Center

  PRINCIPAL INVESTIGATOR

• Noel Clarke, M.D.

  Christie Hospital Foundation Trust

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

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: September 28, 2018
• First Posted: November 7, 2018
• Study Start: October 31, 2018
• Primary Completion: July 30, 2021
• Study Completion: April 27, 2026
• Last Updated: January 29, 2026
• Results First Posted: June 15, 2023

Record last verified: 2026-01

Locations

FR (6); BR (8); DE (10); JP (18); ES (6); US (28); CZ (4); IT (5); BE (1); CL (4); TU (6); CA (10); KR (6); SL (4); GB (5); NL (3); AU (8)