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

A Randomised, Double-blind, Placebo-controlled, Multicentre Phase III Study of Olaparib Plus Abiraterone Relative to Placebo Plus Abiraterone as First-line Therapy in Men With Metastatic Castration-resistant Prostate Cancer (PROpel Study)

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.

Study Overview

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

Detailed Description

PROpel is a phase III study evaluating the efficacy, safety, and tolerability of olaparib versus placebo when given in addition to abiraterone to patients with metastatic castration-resistant prostate cancer (mCRPC) who have not received prior chemotherapy or new hormonal agents (NHAs) for metastatic castration-resistant prostate cancer (mCRPC) (first-line setting).

Approximately 720 patients globally were planned to be randomized in PROpel in a 1:1 ratio to treatment with either olaparib and abiraterone or placebo and abiraterone. Enrolment had completed with a total of 796 patients randomised. Following the completion of global enrolment, the China cohort will randomise approximately 108 additional patients at sites in China, also in a 1:1 ratio.

Patients will receive oral treatment with olaparib 300 mg twice daily + abiraterone 1000 mg once daily or placebo twice daily + abiraterone 1000 mg once daily. Patients in both treatment groups will also receive either prednisone or prednisolone 5 mg twice daily.

• Study Type: Interventional
• Enrollment (Actual): 895
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Box Hill, Australia, 3128
    • Research Site
  • Darlinghurst, Australia, 2010
    • Research Site
  • Greenslopes, Australia, 4120
    • Research Site
  • Herston, Australia, 4029
    • Research Site
  • Kingswood, Australia, 2747
    • Research Site
  • Kurralta Park, Australia, 5037
    • Research Site
  • St Albans, Australia, 3021
    • Research Site
  • Waratah, Australia, 2298
    • Research Site
• Belgium
  • Ghent, Belgium, 9000
    • Research Site
• Brazil
  • Belo Horizonte, Brazil, 30110-022
    • Research Site
  • Curitiba, Brazil, 80810-050
    • Research Site
  • Fortaleza, Brazil, 60336-232
    • Research Site
  • Porto Alegre, Brazil, 91350-200
    • Research Site
  • Rio de Janeiro, Brazil, 22793-080
    • Research Site
  • São José do Rio Preto, Brazil, 15090-000
    • Research Site
  • São Paulo, Brazil, 04266-010
    • Research Site
  • São Paulo, Brazil, 01221-020
    • Research Site
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2V 1P9
      • Research Site
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Research Site
  • British Columbia
    • Kelowna, British Columbia, Canada, V1Y 5L3
      • Research Site
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 1V7
      • Research Site
  • Ontario
    • London, Ontario, Canada, N6A 5W9
      • Research Site
    • Toronto, Ontario, Canada, M5G 2M9
      • Research Site
    • Toronto, Ontario, Canada, M4N 3M5
      • Research Site
  • Quebec
    • Greenfield Park, Quebec, Canada, J4V 2H1
      • Research Site
    • Montreal, Quebec, Canada, H3T 1E2
      • Research Site
    • Montreal, Quebec, Canada, H2X 3E4
      • Research Site
• Chile
  • Santiago, Chile, 7500787
    • Research Site
  • Santiago, Chile, 7520349
    • Research Site
  • Temuco, Chile, 4781156
    • Research Site
  • Viña del Mar, Chile, 2540488
    • Research Site
• Czechia
  • Brno, Czechia, 656 53
    • Research Site
  • Prague, Czechia, 150 06
    • Research Site
  • Prague, Czechia, 140 59
    • Research Site
  • Prague, Czechia, 120 00
    • Research Site
• France
  • Angers, France, 49033
    • Research Site
  • Besançon, France, 25030
    • Research Site
  • Caen, France, 14076
    • Research Site
  • Pierre-Bénite, France, 69495
    • Research Site
  • Quimper, France, 29107
    • Research Site
  • Vandœuvre-lès-Nancy, France, 54519
    • Research Site
• Germany
  • Bergisch Gladbach, Germany, 51465
    • Research Site
  • Bremen, Germany, 28277
    • Research Site
  • Cologne, Germany, 50968
    • Research Site
  • Duisburg, Germany, 47169
    • Research Site
  • Freiburg im Breisgau, Germany, 79106
    • Research Site
  • Heinsberg, Germany, 52525
    • Research Site
  • Mettmann, Germany, 40822
    • Research Site
  • Nuremberg, Germany, 90419
    • Research Site
  • Nürtingen, Germany, 72622
    • Research Site
  • Ulm, Germany, 89081
    • Research Site
• Italy
  • Milan, Italy, 20141
    • Research Site
  • Milan, Italy, 20133
    • Research Site
  • Naples, Italy, 80131
    • Research Site
  • Orbassano, Italy, 10043
    • Research Site
  • Pavia, Italy, 27100
    • Research Site
• Japan
  • Bunkyō City, Japan, 113-8431
    • Research Site
  • Hirakata-shi, Japan, 573-1191
    • Research Site
  • Kanazawa, Japan, 920-8641
    • Research Site
  • Kashihara-shi, Japan, 634-8522
    • Research Site
  • Kawagoe-shi, Japan, 350-8550
    • Research Site
  • Kita-gun, Japan, 761-0793
    • Research Site
  • Kyoto, Japan, 606-8507
    • Research Site
  • Maebashi, Japan, 371-8811
    • Research Site
  • Miyazaki, Japan, 889-1692
    • Research Site
  • Nagoya, Japan, 466-8560
    • Research Site
  • Osaka, Japan, 545-8586
    • Research Site
  • Osaka, Japan, 541-8567
    • Research Site
  • Osakasayama-shi, Japan, 589-8511
    • Research Site
  • Sagamihara-shi, Japan, 252-0375
    • Research Site
  • Sakura-shi, Japan, 285-8741
    • Research Site
  • Shinjuku-ku, Japan, 160-8582
    • Research Site
  • Toon-shi, Japan, 791-0295
    • Research Site
  • Yokohama, Japan, 232-0024
    • Research Site
• Netherlands
  • Hilversum, Netherlands, 1213 XZ
    • Research Site
  • Nijmegen, Netherlands, 6525 GA
    • Research Site
  • Tilburg, Netherlands, 5042 AD
    • Research Site
• Slovakia
  • Bratislava, Slovakia, 851 05
    • Research Site
  • Prešov, Slovakia, 08001
    • Research Site
  • Trenčín, Slovakia, 911 01
    • Research Site
  • Šaľa, Slovakia, 92701
    • Research Site
• South Korea
  • Daegu, South Korea, 41404
    • Research Site
  • Goyang-si, South Korea, 10408
    • Research Site
  • Seoul, South Korea, 03080
    • Research Site
  • Seoul, South Korea, 03722
    • Research Site
  • Seoul, South Korea, 05505
    • Research Site
  • Seoul, South Korea, 06591
    • Research Site
• Spain
  • Barcelona, Spain, 08036
    • Research Site
  • Girona, Spain, 17007
    • Research Site
  • Madrid, Spain, 28041
    • Research Site
  • Madrid, Spain, 08035
    • Research Site
  • Málaga, Spain, 29010
    • Research Site
  • Seville, Spain, 41009
    • Research Site
• Turkey (Türkiye)
  • Adana, Turkey (Türkiye), 01060
    • Research Site
  • Ankara, Turkey (Türkiye), 06800
    • Research Site
  • Ankara, Turkey (Türkiye), 06590
    • Research Site
  • Cordaleo, Turkey (Türkiye), 35575
    • Research Site
  • Istanbul, Turkey (Türkiye), 34030
    • Research Site
  • Izmir, Turkey (Türkiye), 35360
    • Research Site
• United Kingdom
  • Guildford, United Kingdom, GU2 7WG
    • Research Site
  • Manchester, United Kingdom, M20 4BX
    • Research Site
  • Sheffield, United Kingdom, S10 2SJ
    • Research Site
  • Southampton, United Kingdom, SO16 6YD
    • Research Site
  • Swansea, United Kingdom, SA2 8QA
    • Research Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35209
      • Research Site
  • Alaska
    • Anchorage, Alaska, United States, 99503
      • Research Site
  • Arizona
    • Tucson, Arizona, United States, 85704
      • Research Site
    • Tucson, Arizona, United States, 85741
      • Research Site
  • California
    • Clovis, California, United States, 93611
      • Research Site
    • Los Angeles, California, United States, 90027
      • Research Site
    • Los Angeles, California, United States, 90073
      • Research Site
    • Sacramento, California, United States, 95817
      • Research Site
    • San Diego, California, United States, 92123
      • Research Site
  • Colorado
    • Denver, Colorado, United States, 80211
      • Research Site
  • Illinois
    • Lisle, Illinois, United States, 60532
      • Research Site
  • Indiana
    • Jeffersonville, Indiana, United States, 47130
      • Research Site
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Research Site
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Research Site
    • Grand Rapids, Michigan, United States, 49503
      • Research Site
  • Missouri
    • St Louis, Missouri, United States, 63106
      • Research Site
  • Montana
    • Bozeman, Montana, United States, 59715
      • Research Site
  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • Research Site
  • New Jersey
    • Paramus, New Jersey, United States, 07652
      • Research Site
  • New York
    • Brooklyn, New York, United States, 11220
      • Research Site
    • New Hyde Park, New York, United States, 11042
      • Research Site
    • Rochester, New York, United States, 14642
      • Research Site
    • Syracuse, New York, United States, 13210
      • Research Site
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Research Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Research Site
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Research Site
    • Myrtle Beach, South Carolina, United States, 29572
      • Research Site
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 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.
2. Provision of signed and dated, written informed consent form prior to any mandatory study specific procedures, sampling, and analyses.

3. For inclusion in i) the optional exploratory genetic research and ii) the optional biomarker research, patients must fulfill the following criteria:

   • 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.

4. 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.
5. Histologically or cytologically confirmed prostate adenocarcinoma.
6. 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.
7. First-line metastatic castration-resistant prostate cancer (mCRPC).
8. 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.
9. Candidate for abiraterone therapy with documented evidence of progressive disease.
10. Patients must have normal organ and bone marrow function measured within 28 days prior to administration of study treatment.
11. Eastern Cooperative Oncology Group (ECOG) performance status 0-1, with no deterioration over the previous 2 weeks.
12. The participant has, in the opinion of the investigator, a life expectancy of at least 6 months.
13. 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.
14. Male patients must use a condom during treatment and for 3 months after the last dose of olaparib+abiraterone when having sexual intercourse with a pregnant woman or with a woman of childbearing potential. Female partners of male patients should also use a highly effective form of contraception if they are of childbearing potential.

Exclusion Criteria:

1. Has a known additional malignancy that has had progression or has required active treatment in the last 5 years.
2. Patients with myelodysplastic syndrome (MDS)/ acute myeloid leukaemia (AML) or with features suggestive of yelodysplastic syndrome (MDS)/ acute myeloid leukaemia (AML).
3. 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.
4. Planned or scheduled cardiac surgery or percutaneous coronary intervention procedure.
5. Prior revascularisation procedure (significant coronary, carotid, or peripheral artery stenosis).
6. Uncontrolled hypertension (systolic blood pressure (BP) ≥160 millimeters of mercury (mmHg) or diastolic blood pressure (BP) ≥95 millimeters of mercury (mmHg)).
7. History of uncontrolled pituitary or adrenal dysfunction.
8. Active infection or other medical condition that would make prednisone/prednisolone use contraindicated.
9. Any chronic medical condition requiring a systemic dose of corticosteroid >10 milligrams (mg) prednisone/prednisolone per day.
10. Patients who are considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection.
11. Persistent toxicities (Common Terminology Criteria for Adverse Events [CTCAEs] grade >2) caused by previous cancer therapy, excluding alopecia.
12. Patients with brain metastases. A scan to confirm the absence of brain metastases is not required.
13. 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.
14. Patients who are unevaluable for both bone and soft tissue progression
15. Patients who are unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication.
16. Immunocompromised patients
17. Patients with known active hepatitis infection (ie, hepatitis B or C).
18. Any previous treatment with Polyadenosine 5'diphosphoribose [poly (ADP ribose)] polymerase (PARP) inhibitor, including olaparib.
19. Patients receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within 3 weeks prior to study treatment. Patients who receive palliative radiotherapy need to stop radiotherapy 1 week before randomisation.
20. Any previous exposure to a Cytochrome P450 (CYP) 17 (17α-hydroxylase/C17,20-lyase) inhibitor (eg, abiraterone, orteronel).
21. Concomitant use of known strong Cytochrome P450 (CYP) 3A inhibitors (eg, itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (eg, ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting study treatment is 2 weeks.
22. Concomitant use of known strong Cytochrome P450 (CYP) 3A inducers (eg, phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine or St John's wort) or moderate Cytochrome P450 (CYP) 3A inducers (eg, bosentan, efavirenz or modafinil). The required period prior to starting study treatment is 5 weeks for phenobarbital and enzalutamide and 3 weeks for other agents.
23. Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery.
24. Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT).
25. Participation in another clinical study with an investigational product or investigational medical devices within 1 month of randomisation.
26. History of hypersensitivity to olaparib or abiraterone, any of the excipients of olaparib or abiraterone, or drugs with a similar chemical structure or class to olaparib or abiraterone.
27. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca and Merck staff and/or staff at the study site).
28. Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements.
29. Previous randomisation in the present study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: olaparib plus abiraterone; 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; 300 mg (2 x 150 milligrams (mg) tablets) twice daily; Other Names: Lynparza; Drug: abiraterone acetate; 1000 milligrams (mg) once daily; Other Names: Zytiga
Placebo Comparator: placebo plus abiraterone; 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; 1000 milligrams (mg) once daily; Other Names: Zytiga

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Overall Survival (OS) Event	An OS event is defined as death by any cause, regardless of whether the patient withdraws from randomised therapy or receives another anticancer therapy.	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	A TFST (excluding radiotherapy) event is defined as the start of the first subsequent anticancer therapy after discontinuation of randomised treatment or death from any cause.	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	A TTPP event is defined as pain progression based on the Brief Pain Inventory-Short Form (BPI-SF) Item 3 (range 0-10, a higher score indicates worse pain) and opiate analgesic use (Analgesic quantification algorithm [AQA] score, range 0-7, a higher score indicates increased opioid use). For patients who are asymptomatic at baseline (average worst pain score of 0 and not taking opioids): A ≥2 point change from baseline in average (4-7 days) worst pain score observed at 2 consecutive visits or initiation of opioid use; For patients who are symptomatic at baseline (average worst pain score >0 and/or receiving opioids): A ≥2 point change from baseline in average (4-7 days) worst pain score observed at 2 consecutive visits and an average worst pain score ≥4, and no decrease in average opioid use (≥1-point decrease in AQA score from a starting value of ≥2), or increase in opioid use (≥1-point increase, or ≥2-point increase if the starting value is 0) at 2 consecutive follow-up visits.	Assessed from date of randomisation to data cut off (DCO3): 12Oct2022 (Approx. 3 years 11 months)
Number of Participants With Opiate Use	An event for opiate use is defined as the first opiate use for cancer related pain.	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)	An SSRE event is defined as the first sympomatic skeletal-related event defined by; Use of radiation therapy to prevent or relieve skeletal symptoms.; Occurrence of new symptomatic pathological bone fractures (vertebral or non-vertebral).	Assessed from date of randomisation to data cut off (DCO3): 12Oct2022 (Approx. 3 years 11 months)
Number of Participants With Second Progression or Death (PFS2) Event	An event for PFS2 is defined as the second progression on next-line anticancer therapy or death, whichever occurs earlier.	Assessed from date of randomisation to data cut off (DCO3): 12Oct2022 (Approx. 3 years 11 months)
Brief Pain Inventory-Short Form (BPI-SF)	The BPI-SF is a validated, 15-item domain-specific instrument designed to assess the severity of pain and the impact/interference of pain on daily functions. BPI-SF worst pain, pain severity and pain interference score changes can be a minimum of -10 and a maximum of 10. A negative change from baseline value indicates improvement.	Assessed from date of randomisation to data cut off (DCO3): 12Oct2022 (Approx. 3 years 11 months)
Functional Assessment of Cancer Therapy- Prostate Cancer (FACT-P)	Functional Assessment of Cancer Therapy-Prostate Cancer (FACT-P) total score and Functional Assessment of Cancer Therapy-General (FACT-G) total score. Total FACT-P score is the sum of Physical Well-being (PWB), Social Well-being (SWB), Emotional Well-being (EWB), Functional Well-being (FWB) and Prostate cancer subscale (PCS). FACT-P total score change from baseline values can be a minimum of -156 and a maximum of 156. A positive value indicates improvement. FACT-G total score is the sum of PWB, SWB, EWB and FWB. FACT-G Total score change from baseline values can be a minimum of -108 and a maximum of 108. A positive value indicates improvement.	Assessed from date of randomisation to data cut off (DCO3): 12Oct2022 (Approx. 3 years 11 months)

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Principal Investigator: Fred Saad, MD, University of Montreal Hospital Center; Principal Investigator: Noel Clarke, M.D., Christie Hospital Foundation Trust

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• Armstrong AJ, Saad F, Oya M, Shore N, Procopio G, Arslan C, Mehra N, Brown E, Joung JY, Sugimoto M, Ozguroglu M, Gedye C, Sartor O, Poehlein C, Qiu P, Liu YZ, Li X, Harrington EA, McGuinness D, Kang J, Barnicle A, Clarke N. Detection of Homologous Recombination Repair Gene Mutations by Tumor Tissue and Circulating Tumor DNA Testing in Prostate Cancer in the Phase III PROpel Trial. JCO Precis Oncol. 2026 May;10(5):e2501109. doi: 10.1200/PO-25-01109. Epub 2026 May 11.
• 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.

Helpful Links

• Redacted CSR synopsis
• Redacted SAP
• csp_final_compressed
• CSR Addendum 1
• CSR addendum 2 - synopsis

Study record dates

Study Major Dates

• Study Start (Actual): October 31, 2018
• Primary Completion (Actual): July 30, 2021
• Study Completion (Estimated): February 5, 2027

Study Registration Dates

• First Submitted: September 28, 2018
• First Submitted That Met QC Criteria: November 5, 2018
• First Posted (Actual): November 7, 2018

Study Record Updates

• Last Update Posted (Actual): August 18, 2026
• Last Update Submitted That Met QC Criteria: August 17, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: metastatic castration-resistant prostate cancer (mCRPC)
• 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; Steroids; Fused-Ring Compounds; Androstenes; Androstanes; Abiraterone Acetate; olaparib
• Other Study ID Numbers: D081SC00001; 2018-002011-10 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No