Metastatic Castration-resistant Prostate CancerPhase 3NCT02987543
Study of Olaparib (Lynparza™) Versus Enzalutamide or Abiraterone Acetate in Men With Metastatic Castration-Resistant Prostate Cancer (PROfound Study)
A Phase 3 study testing olaparib, enzalutamide and abiraterone acetate in people with Metastatic Castration-resistant Prostate Cancer, run by AstraZeneca at 204 sites in 20 countries.
Trial summary
The purpose of this study is to evaluate the efficacy and safety of olaparib versus enzalutamide or abiraterone acetate in subjects with metastatic castration-resistant prostate cancer who have failed prior treatment with a new hormonal agent and have homologous recombination repair gene mutations. Read more about this study
- Who is it for?
- Ages 18 to 130 years, men only
- Conditions the study is for
- Metastatic Castration-resistant Prostate Cancer
- What is being tested?
- olaparib, enzalutamide and abiraterone acetate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 387 participants
- Where
- 204 sitesin 20 countries
- Study dates
- 6 Feb 2017to 15 Feb 2023
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 130 years
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed diagnosis of prostate cancer.
- Documented evidence of metastatic castration resistant prostate cancer (mCRPC).
- 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 .
- Ongoing therapy with LHRH analog or bilateral orchiectomy.
- Radiographic progression at study entry while on androgen deprivation therapy (or after bilateral orchiectomy).
- Qualifying HRR mutation in tumor tissue.
Who cannot join
- Any previous treatment with PARP inhibitor, including olaparib.
- Subjects who have any previous treatment with DNA-damaging cytotoxic chemotherapy, except if for non-prostate cancer indication and last dose > 5 years prior to randomization.
- Other malignancy (including MDS and MGUS) within the last 5 years except: adequately treated non-melanoma skin cancer or other solid tumors curatively treated with no evidence of disease for ≥5 years.
- Subjects with known brain metastases.
Trial locations and contacts
204 sites in 20 countries.
204 sites in 20 countries
United States35 sites
Research Site
Albany, New York, 12208
Research Site
Anchorage, Alaska, 99503
Research Site
Atlanta, Georgia, 30318
Research Site
Baltimore, Maryland, 21287
Research Site
Brooklyn, New York, 11201
Research Site
Charleston, South Carolina, 29401
Research Site
Chicago, Illinois, 60611
Research Site
Columbus, Ohio, 43230
Research Site
Duarte, California, 91010
Research Site
Durham, North Carolina, 27710
Research Site
Germantown, Tennessee, 38138
Research Site
Jeffersonville, Indiana, 47130
Research Site
Las Vegas, Nevada, 89135
Research Site
Myrtle Beach, South Carolina, 29572
Research Site
Nashville, Tennessee, 37232
Research Site
New Orleans, Louisiana, 70112
Research Site
Oklahoma City, Oklahoma, 73104
Research Site
Omaha, Nebraska, 68130
Research Site
Salisbury, North Carolina, 28144
Research Site
Salt Lake City, Utah, 84112
Research Site
Salt Lake City, Utah, 84148
Research Site
San Antonio, Texas, 78229
Research Site
San Diego, California, 92161
Research Site
Santa Barbara, California, 93105
Research Site
Spokane, Washington, 99202
Research Site
Springfield, Oregon, 97477
Research Site
Syracuse, New York, 13210
Research Site
Tampa, Florida, 33612
Research Site
The Bronx, New York, 10468
Research Site
Towson, Maryland, 21204
Research Site
Tualatin, Oregon, 97062
Research Site
Tucson, Arizona, 85704
Research Site
Tucson, Arizona, 85741
Research Site
Washington D.C., District of Columbia, 20007
Research Site
Wheeling, West Virginia, 26003
Japan30 sites
Research Site
Bunkyō City, 113-8431
Research Site
Bunkyō City, 113-8510
Research Site
Bunkyō City, 113-8603
Research Site
Fukuoka, 812-8582
Research Site
Hirosaki-shi, 036-8563
Research Site
Kanazawa, 920-8641
Research Site
Kashihara-shi, 634-8522
Research Site
Kashiwa, 277-8577
Research Site
Kawagoe-shi, 350-8550
Research Site
Kita-gun, 761-0793
Research Site
Kōtoku, 135-8550
Research Site
Kyoto, 606-8507
Research Site
Maebashi, 371-8811
Research Site
Matsuyama, 791-0280
Research Site
Minatoku, 105-8471
Research Site
Mitaka-shi, 181-8611
Research Site
Miyazaki, 889-1692
Research Site
Nagasaki, 852-8501
Research Site
Nagoya, 464-8681
Research Site
Nagoya, 466-8560
Research Site
Osaka, 541-8567
Research Site
Osaka, 545-8586
Research Site
Osakasayama-shi, 589-8511
Research Site
Sagamihara-shi, 252-0375
Research Site
Sakura-shi, 285-8741
Research Site
Sapporo, 060-8648
Research Site
Shinjuku-ku, 160-8582
Research Site
Suita-shi, 565-0871
Research Site
Sunto-gun, 411-8777
Research Site
Yokohama, 232-0024
Germany15 sites
Research Site
Bergisch Gladbach, 51465
Research Site
Berlin, 13055
Research Site
Bremen, 28277
Research Site
Cologne, 50968
Research Site
Duisburg, 47179
Research Site
Düsseldorf, 40225
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Hamburg, 22399
Research Site
Heidelberg, 69120
Research Site
Holzminden, 37603
Research Site
Jena, 07747
Research Site
Magdeburg, 39120
Research Site
Nuremberg, 90491
Research Site
Nürtingen, 72622
Research Site
Tübingen, 72076
Research Site
Wuppertal, 42109
Brazil14 sites
Research Site
Barretos, 14784-400
Research Site
Belo Horizonte, 30110-022
Research Site
Curitiba, 80530-010
Research Site
Florianópolis, 88034-000
Research Site
Passo Fundo, 99010-080
Research Site
Porto Alegre, 90160-093
Research Site
Porto Alegre, 90610-000
Research Site
Recife, 50040-000
Research Site
Ribeirão Preto, 14015-140
Research Site
Rio de Janeiro, 22793-080
Research Site
Santo André, 09060-650
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São José do Rio Preto, 15090-000
Research Site
São Paulo, 01321-001
Research Site
São Paulo, 03102-002
France13 sites
Research Site
Besançon, 25030
Research Site
Bordeaux, 33000
Research Site
Caen, 14000
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Lille, 59020
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Lyon, 69008
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Marseille, 13273
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Montpellier, 34298
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Paris, 75014
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Poitiers, 86021
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Saint-Herblain, 44805
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Toulouse, 31100
Research Site
Vandœuvre-lès-Nancy, 54519
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Villejuif, 94805
Canada12 sites
Research Site
Chicoutimi, Quebec, G7H 5H6
Research Site
Edmonton, Alberta, T6G 1Z2
Research Site
Hamilton, Ontario, L8V 5C2
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Kelowna, British Columbia, V1Y 5L3
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Montreal, Quebec, H2X 3E4
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Montreal, Quebec, H4A 3J1
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Oakville, Ontario, L6H 3P1
Research Site
Québec, Quebec, G1J 1Z4
Research Site
Saskatoon, Saskatchewan, S7N 4H4
Research Site
Toronto, Ontario, M4N 3M5
Research Site
Toronto, Ontario, M5G 2M9
Research Site
Vancouver, British Columbia, V5Z 4E6
Australia10 sites
Research Site
Adelaide, 5000
Research Site
Box Hill, 3128
Research Site
Clayton, 3168
Research Site
Greenslopes, 4120
Research Site
Herston, 4029
Research Site
Macquarie University, 2109
Research Site
Melbourne, 3000
Research Site
Nedlands, 6009
Research Site
Randwick, 2031
Research Site
Waratah, 2298
Italy10 sites
Research Site
Ancona, 60126
Research Site
Arezzo, 52100
Research Site
Bari, 70124
Research Site
Brescia, 25100
Research Site
Meldola, 47014
Research Site
Milan, 20133
Research Site
Milan, 20141
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Modena, 41124
Research Site
Naples, 80131
Research Site
Trento, 38100
South Korea9 sites
Research Site
Busan, 49241
Research Site
Daegu, 41404
Research Site
Goyang-si, 10408
Research Site
Gwangju, 61469
Research Site
Seoul, 03722
Research Site
Seoul, 05505
Research Site
Seoul, 06273
Research Site
Seoul, 06351
Research Site
Seoul, 06591
Taiwan9 sites
Research Site
Changhua, 50006
Research Site
Kaohsiung City, 807
Research Site
Kaohsiung City, 833
Research Site
Taichung, 404
Research Site
Taichung, 40705
Research Site
Tainan, 70403
Research Site
Taipei, 10002
Research Site
Taipei, 112
Research Site
Taoyuan City, 333
Turkey (Türkiye)8 sites
Research Site
Adana, 01120
Research Site
Ankara, 06230
Research Site
Ankara, 06340
Research Site
Ankara, 06590
Research Site
Cordaleo, 35575
Research Site
Edirne, 22030
Research Site
Istanbul, 34030
Research Site
Istanbul, 34365
Spain7 sites
Research Site
Girona, 17007
Research Site
Madrid, 08035
Research Site
Madrid, 28040
Research Site
Madrid, 28041
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Málaga, 29010
Research Site
Oviedo, 33011
Research Site
Seville, 41009
Argentina6 sites
Research Site
Buenos Aires, 1426
Research Site
Buenos Aires, C1118AAT
Research Site
Buenos Aires, C1120AAT
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CABA, C1280AEB
Research Site
La Rioja, 5300
Research Site
Rosario, 2000
Israel6 sites
Research Site
Haifa, 31096
Research Site
Jerusalem, 91120
Research Site
Kfar Saba, 95847
Research Site
Petah Tikva, 4941492
Research Site
Ramat Gan, 5265601
Research Site
Tsrifin, 70300
Netherlands6 sites
Research Site
Amsterdam, 1066 CX
Research Site
Hilversum, 1213 XZ
Research Site
Leiden, 2333 ZA
Research Site
Nijmegen, 6525 GA
Research Site
Tilburg, 5042 AD
Research Site
Zwolle, 8025 AB
Austria5 sites
Research Site
Graz, 8036
Research Site
Linz, 4020
Research Site
Salzburg, 5020
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Vienna, 1020
Research Site
Vienna, 1090
United Kingdom5 sites
Research Site
London, EC1M 6BQ
Research Site
London, NW1 2PG
Research Site
Manchester, M20 4BX
Research Site
Romford, RM7 0BE
Research Site
Sutton, SM25PT
About this study
Official title: A Phase III, Open Label, Randomized Study to Assess the Efficacy and Safety of Olaparib (Lynparza™) Versus Enzalutamide or Abiraterone Acetate in Men With Metastatic Castration-Resistant Prostate Cancer Who Have Failed Prior Treatment With a New Hormonal Agent and Have Homologous Recombination Repair Gene Mutations (PROfound)
The purpose of this study is to evaluate the efficacy and safety of olaparib versus enzalutamide or abiraterone acetate in subjects with metastatic castration-resistant prostate cancer who have failed prior treatment with a new hormonal agent and have homologous recombination repair gene mutations.
Read the detailed description
This is a prospective, multicenter, randomized, open-label, phase 3 trial evaluating the efficacy and safety of olaparib versus enzalutamide or abiraterone in subjects with metastatic castration-resistant prostate cancer (mCRPC) who have failed prior treatment with a new hormonal agent (NHA) and have a qualifying tumor mutation in one of 15 genes involved in the homologous recombination repair (HRR) pathway. Subjects will be divided into two cohorts based on HRR gene mutation status.
Approximately 340 subjects will be randomized 2:1 (olaparib : investigator choice of enzalutamide or abiraterone acetate) into the trial.
- Being tested
- olaparib, enzalutamide, abiraterone acetate
- Keywords
- metastatic castration-resistant prostate cancer (mCRPC), homologous recombination repair (HRR)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
olaparibDrug
Also called Lynparza
300 mg (2x 150 mg tablets) twice daily
enzalutamideDrug
Also called XTANDI
160 mg (4 x 40 mg capsules) once daily
abiraterone acetateDrug
Also called ZYTIGA
1,000 mg (4 x 250 mg tablets) once daily
abiraterone acetateDrug
Also called ZYTIGA
1,000 mg (2 x 500 mg tablets) once daily
enzalutamideDrug
Also called XTANDI
160 mg (4 x 40 mg tablets) once daily
| Study group | Role | What they receive |
|---|---|---|
| Olaparib | Experimental | 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 Receives: Drug: olaparib |
| Enzalutamide OR abiraterone acetate | Active comparator | 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 or 500 mg of abiraterone acetate. Subjects will be administered study treatment orally at a dose of 1,000 mg once daily in combination with prednisone 5 mg administered twice daily orally. Prednisolone is permitted for use instead of prednisone if necessary. Receives: Drug: enzalutamide; Drug: abiraterone acetate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Radiological Progression Free Survival (rPFS) by Blinded Independent Central Review (BICR) - Cohort A Only
The time from randomisation until the date of objective radiological disease progression (determined by RECIST 1.1 (soft tissue) and Prostate Cancer Working Group 3 (PCWG-3) (bone)) or death (by any cause in the absence of progression) regardless of whether the patient withdrew from randomised therapy or received another anti-cancer therapy prior to progression. Progression is defined using (i) Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for soft tissue, as a >=20% increase in the sum of diameters of target lesions and an absolute increase of >=5mm taking as reference the smallest sum of diameters since treatment started including the baseline sum of diameters; (ii) Prostate Cancer Working Group 3 (PGWG-3) for bone as >= 2 new bone lesions on the 1st week 8 scan compared to baseline. The confirmatory scan, >=6 weeks later, must show >=2 more new bone lesions (for a total of >=4 new bone lesions since baseline).
Measured: Tumor assessments every 8 weeks from randomisation until radiographic progression assessed by BICR (median duration of treatment of 7 and 4 months for Olaparib and Investigators Choice of NHA respectively).
Secondary outcomes (4)
Confirmed Objective Response Rate (ORR) by Blinded Independent Central Review (BICR) - Cohort A Only
ORR is the percentage of patients with at least one visit response of Complete response (CR) or Partial response (PR), in their soft tissue disease assessed by Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), in the absence of progression on bone scan assessed by Prostate Cancer Working Group 3 (PCWG3)). 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, ORR is the number of patients with a CR and PR.
Measured: Tumor assessments every 8 weeks from randomisation until radiographic progression assessed by BICR (median duration of treatment of 7 and 4 months for Olaparib and Investigators Choice of NHA respectively).
Radiological Progression Free Survival (rPFS) by Blinded Independent Central Review (BICR) - Cohort A+B
The time from randomisation until the date of objective radiological disease progression (by RECIST 1.1 and Prostate Cancer Working Group 3 (PGWG-3)) or death (by any cause in the absence of progression) regardless of whether the patient withdrew from randomised therapy or received another anti-cancer therapy prior to progression.
Measured: Tumor assessments every 8 weeks from randomisation until radiographic progression assessed by BICR (median duration of treatment of 7 and 4 months for Olaparib and Investigators Choice of NHA respectively).
Time to Pain Progression - Cohort A Only
Time from randomisation to time point at which worsening in pain is observed (ie date of pain progression - date of randomisation + 1). Based on average Brief Pain Inventory - short form (BPI-SF) worst pain [Item 3] and Analgesic Quantification Algorithm [AQA] score.
Measured: Every 4 weeks from randomisation (for 7 consecutive days) throughout the study (median duration of treatment of 7 and 4 months for Olaparib and Investigators Choice of NHA respectively).
Overall Survival (OS) - Cohort A Only
Number of Participants with Overall Survival (OS) - Cohort A only.
Measured: Approximately 35 months after the first patient was randomised.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Dec 2016 (estimated)
- Study start6 Feb 2017
- Primary completion4 Jun 2019
- Study completion15 Feb 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Metastatic Castration-resistant Prostate CancerStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 387 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Merck Sharp & Dohme LLC, Foundation Medicine, Myriad Genetics, Inc.
- Responsible party
- Sponsor
- Investigators
- Johann de Bono, M.D., Ph.D., Principal investigator, The Institute of Cancer Research, United KingdomMaha Hussain, M.D., FACP, FASCO, Principal investigator, Northwestern University, United States of America
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02987543
- Sponsor's protocol ID
- D081DC00007
- Other IDs
- 2016-000300-28, 2016
- Status last verified
- Sep 2023
- First submitted
- 15 Nov 2016
- Last updated
- 6 Oct 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Mayerhoefer ME, Kienzle A, Woo S, Vargas HA. Update on Liquid Biopsy. Radiology. 2025 Jun;315(3):e241030. doi: 10.1148/radiol.241030.
PubMed 40525978Mateo J, de Bono JS, Fizazi K, Saad F, Shore N, Sandhu S, Chi KN, Agarwal N, Olmos D, Thiery-Vuillemin A, Ozguroglu M, Mehra N, Matsubara N, Young Joung J, Padua C, Korbenfeld E, Kang J, Marshall H, Lai Z, Barnicle A, Poehlein C, Lukashchuk N, Hussain M. Olaparib for the Treatment of Patients With Metastatic Castration-Resistant Prostate Cancer and Alterations in BRCA1 and/or BRCA2 in the PROfound Trial. J Clin Oncol. 2024 Feb 10;42(5):571-583. doi: 10.1200/JCO.23.00339. Epub 2023 Nov 14.
PubMed 37963304Roubaud G, Ozguroglu M, Penel N, Matsubara N, Mehra N, Kolinsky MP, Procopio G, Feyerabend S, Joung JY, Gravis G, Nishimura K, Gedye C, Padua C, Shore N, Thiery-Vuillemin A, Saad F, van Alphen R, Carducci MA, Desai C, Brickel N, Poehlein C, Del Rosario P, Fizazi K. Olaparib tolerability and common adverse-event management in patients with metastatic castration-resistant prostate cancer: Further analyses from the PROfound study. Eur J Cancer. 2022 Jul;170:73-84. doi: 10.1016/j.ejca.2022.04.016. Epub 2022 May 19.
PubMed 35598359Matsubara N, Nishimura K, Kawakami S, Joung JY, Uemura H, Goto T, Kwon TG, Sugimoto M, Kato M, Wang SS, Pang ST, Chen CH, Fujita T, Nii M, Shen L, Dujka M, Hussain M, de Bono J. Olaparib in patients with mCRPC with homologous recombination repair gene alterations: PROfound Asian subset analysis. Jpn J Clin Oncol. 2022 May 5;52(5):441-448. doi: 10.1093/jjco/hyac015.
PubMed 35229141Thiery-Vuillemin A, de Bono J, Hussain M, Roubaud G, Procopio G, Shore N, Fizazi K, Dos Anjos G, Gravis G, Joung JY, Matsubara N, Castellano D, Degboe A, Gresty C, Kang J, Allen A, Poehlein C, Saad F. Pain and health-related quality of life with olaparib versus physician's choice of next-generation hormonal drug in patients with metastatic castration-resistant prostate cancer with homologous recombination repair gene alterations (PROfound): an open-label, randomised, phase 3 trial. Lancet Oncol. 2022 Mar;23(3):393-405. doi: 10.1016/S1470-2045(22)00017-1. Epub 2022 Feb 11.
PubMed 35157830Hussain M, Corcoran C, Sibilla C, Fizazi K, Saad F, Shore N, Sandhu S, Mateo J, Olmos D, Mehra N, Kolinsky MP, Roubaud G, Ozguroglu M, Matsubara N, Gedye C, Choi YD, Padua C, Kohlmann A, Huisden R, Elvin JA, Kang J, Adelman CA, Allen A, Poehlein C, de Bono J. Tumor Genomic Testing for >4,000 Men with Metastatic Castration-resistant Prostate Cancer in the Phase III Trial PROfound (Olaparib). Clin Cancer Res. 2022 Apr 14;28(8):1518-1530. doi: 10.1158/1078-0432.CCR-21-3940.
PubMed 35091440Hussain M, Mateo J, Fizazi K, Saad F, Shore N, Sandhu S, Chi KN, Sartor O, Agarwal N, Olmos D, Thiery-Vuillemin A, Twardowski P, Roubaud G, Ozguroglu M, Kang J, Burgents J, Gresty C, Corcoran C, Adelman CA, de Bono J; PROfound Trial Investigators. Survival with Olaparib in Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2020 Dec 10;383(24):2345-2357. doi: 10.1056/NEJMoa2022485. Epub 2020 Sep 20.
PubMed 32955174de Bono J, Mateo J, Fizazi K, Saad F, Shore N, Sandhu S, Chi KN, Sartor O, Agarwal N, Olmos D, Thiery-Vuillemin A, Twardowski P, Mehra N, Goessl C, Kang J, Burgents J, Wu W, Kohlmann A, Adelman CA, Hussain M. Olaparib for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2020 May 28;382(22):2091-2102. doi: 10.1056/NEJMoa1911440. Epub 2020 Apr 28.
PubMed 32343890
Study at a glance
From the registry record, last updated by the sponsor on 6 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III, Open Label, Randomized Study to Assess the Efficacy and Safety of Olaparib (Lynparza™) Versus Enzalutamide or Abiraterone Acetate in Men With Metastatic Castration-Resistant Prostate Cancer Who Have Failed Prior Treatment With a New Hormonal Agent and Have Homologous Recombination Repair Gene Mutations (PROfound)
- ClinicalTrials.gov ID
- NCT02987543
- Acronym / sponsor ID
- D081DC00007
- Keywords
- metastatic castration-resistant prostate cancer (mCRPC), homologous recombination repair (HRR)
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 387 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Collaborators
- Merck Sharp & Dohme LLC, Foundation Medicine, Myriad Genetics, Inc.
- Study start
- 6 Feb 2017 (actual)
- Primary completion
- 4 Jun 2019 (actual)
- Study completion
- 15 Feb 2023 (actual)
- First posted
- 9 Dec 2016 (estimated)
- Results
- Posted 12 Oct 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the efficacy and safety of olaparib versus enzalutamide or abiraterone acetate in subjects with metastatic castration-resistant prostate cancer who have failed prior treatment with a new hormonal agent and have homologous recombination repair gene mutations.
Detailed description
This is a prospective, multicenter, randomized, open-label, phase 3 trial evaluating the efficacy and safety of olaparib versus enzalutamide or abiraterone in subjects with metastatic castration-resistant prostate cancer (mCRPC) who have failed prior treatment with a new hormonal agent (NHA) and have a qualifying tumor mutation in one of 15 genes involved in the homologous recombination repair (HRR) pathway. Subjects will be divided into two cohorts based on HRR gene mutation status.
Approximately 340 subjects will be randomized 2:1 (olaparib : investigator choice of enzalutamide or abiraterone acetate) into the trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Olaparib | Experimental | Drug: olaparibOlaparib 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 |
| Enzalutamide OR abiraterone acetate | Active comparator | Drug: enzalutamide, Drug: abiraterone acetateEnzalutamide: 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 or 500 mg of abiraterone acetate. Subjects will be administered study treatment orally at a dose of 1,000 mg once daily in combination with prednisone 5 mg administered twice daily orally. Prednisolone is permitted for use instead of prednisone if necessary. |
Who may qualify
- Ages
- 18 to 130 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Histologically confirmed diagnosis of prostate cancer.
- Documented evidence of metastatic castration resistant prostate cancer (mCRPC).
- 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 .
- Ongoing therapy with LHRH analog or bilateral orchiectomy.
- Radiographic progression at study entry while on androgen deprivation therapy (or after bilateral orchiectomy).
Key exclusion criteria (4 listed)
- Any previous treatment with PARP inhibitor, including olaparib.
- Subjects who have any previous treatment with DNA-damaging cytotoxic chemotherapy, except if for non-prostate cancer indication and last dose > 5 years prior to randomization.
- Other malignancy (including MDS and MGUS) within the last 5 years except: adequately treated non-melanoma skin cancer or other solid tumors curatively treated with no evidence of disease for ≥5 years.
- Subjects with known brain metastases.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| olaparibAlso: Lynparza300 mg (2x 150 mg tablets) twice daily | Drug | Olaparib |
| enzalutamideAlso: XTANDI160 mg (4 x 40 mg capsules) once daily | Drug | Enzalutamide OR abiraterone acetate |
| abiraterone acetateAlso: ZYTIGA1,000 mg (4 x 250 mg tablets) once daily | Drug | Enzalutamide OR abiraterone acetate |
| abiraterone acetateAlso: ZYTIGA1,000 mg (2 x 500 mg tablets) once daily | Drug | Enzalutamide OR abiraterone acetate |
| enzalutamideAlso: XTANDI160 mg (4 x 40 mg tablets) once daily | Drug | Enzalutamide OR abiraterone acetate |
Primary outcome
Radiological Progression Free Survival (rPFS) by Blinded Independent Central Review (BICR) - Cohort A Only
Time frame: Tumor assessments every 8 weeks from randomisation until radiographic progression assessed by BICR (median duration of treatment of 7 and 4 months for Olaparib and Investigators Choice of NHA respectively).
The time from randomisation until the date of objective radiological disease progression (determined by RECIST 1.1 (soft tissue) and Prostate Cancer Working Group 3 (PCWG-3) (bone)) or death (by any cause in the absence of progression) regardless of whether the patient withdrew from randomised therapy or received another anti-cancer therapy prior to progression. Progression is defined using (i) Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for soft tissue, as a >=20% increase in the sum of diameters of target lesions and an absolute increase of >=5mm taking as reference the smallest sum of diameters since treatment started including the baseline sum of diameters; (ii) Prostate Cancer Working Group 3 (PGWG-3) for bone as >= 2 new bone lesions on the 1st week 8 scan compared to baseline. The confirmatory scan, >=6 weeks later, must show >=2 more new bone lesions (for a total of >=4 new bone lesions since baseline).
4 secondary outcomes
Confirmed Objective Response Rate (ORR) by Blinded Independent Central Review (BICR) - Cohort A Only
Time frame: Tumor assessments every 8 weeks from randomisation until radiographic progression assessed by BICR (median duration of treatment of 7 and 4 months for Olaparib and Investigators Choice of NHA respectively).
Radiological Progression Free Survival (rPFS) by Blinded Independent Central Review (BICR) - Cohort A+B
Time frame: Tumor assessments every 8 weeks from randomisation until radiographic progression assessed by BICR (median duration of treatment of 7 and 4 months for Olaparib and Investigators Choice of NHA respectively).
Time to Pain Progression - Cohort A Only
Time frame: Every 4 weeks from randomisation (for 7 consecutive days) throughout the study (median duration of treatment of 7 and 4 months for Olaparib and Investigators Choice of NHA respectively).
Overall Survival (OS) - Cohort A Only
Time frame: Approximately 35 months after the first patient was randomised.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Oct 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40525978Mayerhoefer ME, Kienzle A, Woo S, Vargas HA. Update on Liquid Biopsy. Radiology. 2025 Jun;315(3):e241030. doi: 10.1148/radiol.241030.
- Derived from this study: PubMed 37963304Mateo J, de Bono JS, Fizazi K, Saad F, Shore N, Sandhu S, Chi KN, Agarwal N, Olmos D, Thiery-Vuillemin A, Ozguroglu M, Mehra N, Matsubara N, Young Joung J, Padua C, Korbenfeld E, Kang J, Marshall H, Lai Z, Barnicle A, Poehlein C, Lukashchuk N, Hussain M. Olaparib for the Treatment of Patients With Metastatic Castration-Resistant Prostate Cancer and Alterations in BRCA1 and/or BRCA2 in the PROfound Trial. J Clin Oncol. 2024 Feb 10;42(5):571-583. doi: 10.1200/JCO.23.00339. Epub 2023 Nov 14.
- Derived from this study: PubMed 35598359Roubaud G, Ozguroglu M, Penel N, Matsubara N, Mehra N, Kolinsky MP, Procopio G, Feyerabend S, Joung JY, Gravis G, Nishimura K, Gedye C, Padua C, Shore N, Thiery-Vuillemin A, Saad F, van Alphen R, Carducci MA, Desai C, Brickel N, Poehlein C, Del Rosario P, Fizazi K. Olaparib tolerability and common adverse-event management in patients with metastatic castration-resistant prostate cancer: Further analyses from the PROfound study. Eur J Cancer. 2022 Jul;170:73-84. doi: 10.1016/j.ejca.2022.04.016. Epub 2022 May 19.
- Derived from this study: PubMed 35229141Matsubara N, Nishimura K, Kawakami S, Joung JY, Uemura H, Goto T, Kwon TG, Sugimoto M, Kato M, Wang SS, Pang ST, Chen CH, Fujita T, Nii M, Shen L, Dujka M, Hussain M, de Bono J. Olaparib in patients with mCRPC with homologous recombination repair gene alterations: PROfound Asian subset analysis. Jpn J Clin Oncol. 2022 May 5;52(5):441-448. doi: 10.1093/jjco/hyac015.
- Derived from this study: PubMed 35157830Thiery-Vuillemin A, de Bono J, Hussain M, Roubaud G, Procopio G, Shore N, Fizazi K, Dos Anjos G, Gravis G, Joung JY, Matsubara N, Castellano D, Degboe A, Gresty C, Kang J, Allen A, Poehlein C, Saad F. Pain and health-related quality of life with olaparib versus physician's choice of next-generation hormonal drug in patients with metastatic castration-resistant prostate cancer with homologous recombination repair gene alterations (PROfound): an open-label, randomised, phase 3 trial. Lancet Oncol. 2022 Mar;23(3):393-405. doi: 10.1016/S1470-2045(22)00017-1. Epub 2022 Feb 11.
- Derived from this study: PubMed 35091440Hussain M, Corcoran C, Sibilla C, Fizazi K, Saad F, Shore N, Sandhu S, Mateo J, Olmos D, Mehra N, Kolinsky MP, Roubaud G, Ozguroglu M, Matsubara N, Gedye C, Choi YD, Padua C, Kohlmann A, Huisden R, Elvin JA, Kang J, Adelman CA, Allen A, Poehlein C, de Bono J. Tumor Genomic Testing for >4,000 Men with Metastatic Castration-resistant Prostate Cancer in the Phase III Trial PROfound (Olaparib). Clin Cancer Res. 2022 Apr 14;28(8):1518-1530. doi: 10.1158/1078-0432.CCR-21-3940.
- Derived from this study: PubMed 32955174Hussain M, Mateo J, Fizazi K, Saad F, Shore N, Sandhu S, Chi KN, Sartor O, Agarwal N, Olmos D, Thiery-Vuillemin A, Twardowski P, Roubaud G, Ozguroglu M, Kang J, Burgents J, Gresty C, Corcoran C, Adelman CA, de Bono J; PROfound Trial Investigators. Survival with Olaparib in Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2020 Dec 10;383(24):2345-2357. doi: 10.1056/NEJMoa2022485. Epub 2020 Sep 20.
- Derived from this study: PubMed 32343890de Bono J, Mateo J, Fizazi K, Saad F, Shore N, Sandhu S, Chi KN, Sartor O, Agarwal N, Olmos D, Thiery-Vuillemin A, Twardowski P, Mehra N, Goessl C, Kang J, Burgents J, Wu W, Kohlmann A, Adelman CA, Hussain M. Olaparib for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2020 May 28;382(22):2091-2102. doi: 10.1056/NEJMoa1911440. Epub 2020 Apr 28.
- CSP redactedLink provided by the sponsor.
- redacted SAPLink provided by the sponsor.
- Redacted CSR synopsisLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Johann de Bono, M.D., Ph.D. principal investigator
The Institute of Cancer Research, United Kingdom
Maha Hussain, M.D., FACP, FASCO principal investigator
Northwestern University, United States of America
204 sites in 20 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing olaparib, enzalutamide and abiraterone acetate in people with Metastatic Castration-resistant Prostate Cancer, run by AstraZeneca at 204 sites in 20 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 204 sites in United States, Japan, Germany, Brazil, France and 15 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Oct 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Radiological Progression Free Survival (rPFS) by Blinded Independent Central Review (BICR) - Cohort A Only (time frame: Tumor assessments every 8 weeks from randomisation until radiographic progression assessed by BICR (median duration of treatment of 7 and 4 months for Olaparib and Investigators Choice of NHA respectively).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02987543, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Oct 2023.