Study of Olaparib (Lynparza™) Versus Enzalutamide or Abiraterone Acetate in Men With Metastatic Castration-Resistant Prostate Cancer (PROfound Study)
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)
2 other identifiers
interventional
387
19 countries
194
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Feb 2017
Longer than P75 for phase_3
194 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 15, 2016
CompletedFirst Posted
Study publicly available on registry
December 9, 2016
CompletedStudy Start
First participant enrolled
February 6, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 4, 2019
CompletedResults Posted
Study results publicly available
October 12, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
February 15, 2023
CompletedOctober 6, 2023
September 1, 2023
2.3 years
November 15, 2016
June 3, 2020
October 4, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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).
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
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
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
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
Approximately 35 months after the first patient was randomised.
Study Arms (2)
Olaparib
EXPERIMENTALOlaparib 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 COMPARATOREnzalutamide: 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.
Interventions
160 mg (4 x 40 mg capsules) once daily
1,000 mg (4 x 250 mg tablets) once daily
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AstraZenecalead
- Merck Sharp & Dohme LLCcollaborator
- Foundation Medicinecollaborator
- Myriad Genetics, Inc.collaborator
Study Sites (204)
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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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Duarte, California, 91010, United States
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San Diego, California, 92161, United States
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Santa Barbara, California, 93105, United States
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Washington D.C., District of Columbia, 20007, United States
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Tampa, Florida, 33612, United States
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Atlanta, Georgia, 30318, United States
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Chicago, Illinois, 60611, 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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Baltimore, Maryland, 21287, United States
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Towson, Maryland, 21204, United States
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Omaha, Nebraska, 68130, United States
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Las Vegas, Nevada, 89135, United States
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Albany, New York, 12208, United States
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Brooklyn, New York, 11201, United States
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Syracuse, New York, 13210, United States
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The Bronx, New York, 10468, United States
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Durham, North Carolina, 27710, United States
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Salisbury, North Carolina, 28144, United States
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Columbus, Ohio, 43230, United States
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Oklahoma City, Oklahoma, 73104, United States
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Springfield, Oregon, 97477, United States
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Tualatin, Oregon, 97062, United States
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Charleston, South Carolina, 29401, United States
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Myrtle Beach, South Carolina, 29572, United States
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Germantown, Tennessee, 38138, United States
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Nashville, Tennessee, 37232, United States
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San Antonio, Texas, 78229, United States
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Salt Lake City, Utah, 84112, United States
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Salt Lake City, Utah, 84148, United States
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Spokane, Washington, 99202, United States
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Wheeling, West Virginia, 26003, United States
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Buenos Aires, 1426, Argentina
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Buenos Aires, C1118AAT, Argentina
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Buenos Aires, C1120AAT, Argentina
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CABA, C1280AEB, Argentina
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La Rioja, 5300, Argentina
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Rosario, 2000, Argentina
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Adelaide, 5000, Australia
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Box Hill, 3128, Australia
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Clayton, 3168, Australia
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Greenslopes, 4120, Australia
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Herston, 4029, Australia
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Macquarie University, 2109, Australia
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Melbourne, 3000, Australia
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Nedlands, 6009, Australia
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Randwick, 2031, Australia
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Waratah, 2298, Australia
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Graz, 8036, Austria
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Linz, 4020, Austria
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Salzburg, 5020, Austria
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Vienna, 1020, Austria
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Vienna, 1090, Austria
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Barretos, 14784-400, Brazil
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Belo Horizonte, 30110-022, Brazil
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Curitiba, 80530-010, Brazil
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Florianópolis, 88034-000, Brazil
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Passo Fundo, 99010-080, Brazil
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Porto Alegre, 90160-093, Brazil
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Porto Alegre, 90610-000, Brazil
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Recife, 50040-000, Brazil
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Ribeirão Preto, 14015-140, Brazil
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Rio de Janeiro, 22793-080, Brazil
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Santo André, 09060-650, Brazil
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São José do Rio Preto, 15090-000, Brazil
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São Paulo, 01321-001, Brazil
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São Paulo, 03102-002, Brazil
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Edmonton, Alberta, T6G 1Z2, Canada
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Kelowna, British Columbia, V1Y 5L3, Canada
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Vancouver, British Columbia, V5Z 4E6, Canada
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Hamilton, Ontario, L8V 5C2, Canada
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Oakville, Ontario, L6H 3P1, Canada
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Toronto, Ontario, M4N 3M5, Canada
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Toronto, Ontario, M5G 2M9, Canada
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Chicoutimi, Quebec, G7H 5H6, Canada
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Montreal, Quebec, H2X 3E4, Canada
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Montreal, Quebec, H4A 3J1, Canada
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Québec, Quebec, G1J 1Z4, Canada
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Saskatoon, Saskatchewan, S7N 4H4, Canada
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Odense C, 5000, Denmark
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Besançon, 25030, France
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Bordeaux, 33000, France
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Caen, 14000, France
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Lille, 59020, France
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Lyon, 69008, France
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Marseille, 13273, France
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Montpellier, 34298, France
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Paris, 75014, France
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Poitiers, 86021, France
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Saint-Herblain, 44805, France
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Toulouse, 31100, France
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Vandœuvre-lès-Nancy, 54519, France
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Villejuif, 94805, France
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Bergisch Gladbach, 51465, Germany
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Berlin, 13055, Germany
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Bremen, 28277, Germany
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Cologne, 50968, Germany
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Duisburg, 47179, Germany
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Düsseldorf, 40225, Germany
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Hamburg, 22399, Germany
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Heidelberg, 69120, Germany
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Holzminden, 37603, Germany
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Jena, 07747, Germany
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Magdeburg, 39120, Germany
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Nuremberg, 90491, Germany
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Nürtingen, 72622, Germany
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Tübingen, 72076, Germany
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Wuppertal, 42109, Germany
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Haifa, 31096, Israel
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Jerusalem, 91120, Israel
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Kfar Saba, 95847, Israel
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Petah Tikva, 4941492, Israel
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Ramat Gan, 5265601, Israel
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Ẕerifin, 70300, Israel
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Ancona, 60126, Italy
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Arezzo, 52100, Italy
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Bari, 70124, Italy
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Brescia, 25100, Italy
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Meldola, 47014, Italy
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Milan, 20133, Italy
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Milan, 20141, Italy
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Modena, 41124, Italy
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Napoli, 80131, Italy
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Trento, 38100, Italy
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Bunkyō City, 113-8431, Japan
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Bunkyō City, 113-8510, Japan
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Bunkyō City, 113-8603, Japan
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Fukuoka, 812-8582, Japan
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Hirosaki-shi, 036-8563, Japan
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Kanazawa, 920-8641, Japan
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Kashihara-shi, 634-8522, Japan
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Kashiwa, 277-8577, Japan
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Kawagoe-shi, 350-8550, Japan
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Kita-gun, 761-0793, Japan
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Kōtoku, 135-8550, Japan
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Kyoto, 606-8507, Japan
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Maebashi, 371-8811, Japan
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Matsuyama, 791-0280, Japan
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Minatoku, 105-8471, Japan
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Mitaka-shi, 181-8611, Japan
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Miyazaki, 889-1692, Japan
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Nagasaki, 852-8501, Japan
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Nagoya, 464-8681, 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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Sapporo, 060-8648, Japan
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Shinjuku-ku, 160-8582, Japan
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Suita-shi, 565-0871, Japan
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Sunto-gun, 411-8777, Japan
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Yokohama, 232-0024, Japan
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Amsterdam, 1066 CX, Netherlands
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Hilversum, 1213 XZ, Netherlands
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Leiden, 2333 ZA, Netherlands
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Nijmegen, 6525 GA, Netherlands
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Tilburg, 5042 AD, Netherlands
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Zwolle, 8025 AB, Netherlands
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Lørenskog, N-1478, Norway
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Busan, 49241, South Korea
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Daegu, 41404, South Korea
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Goyang-si, 10408, South Korea
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Gwangju, 61469, South Korea
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Seoul, 03722, South Korea
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Seoul, 05505, South Korea
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Seoul, 06273, South Korea
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Seoul, 06351, South Korea
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Seoul, 06591, South Korea
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Girona, 17007, Spain
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Madrid, 08035, Spain
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Madrid, 28040, Spain
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Madrid, 28041, Spain
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Málaga, 29010, Spain
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Oviedo, 33011, Spain
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Seville, 41009, Spain
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Gothenburg, 413 45, Sweden
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Solna, 171 64, Sweden
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Changhua, 50006, Taiwan
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Kaohsiung City, 807, Taiwan
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Kaohsiung City, 833, Taiwan
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Taichung, 404, Taiwan
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Taichung, 40705, Taiwan
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Tainan, 70403, Taiwan
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Taipei, 10002, Taiwan
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Taipei, 112, Taiwan
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Taoyuan, 333, Taiwan
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Adana, 01120, Turkey (Türkiye)
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Ankara, 06230, Turkey (Türkiye)
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Ankara, 06340, Turkey (Türkiye)
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Ankara, 06590, Turkey (Türkiye)
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Edirne, 22030, Turkey (Türkiye)
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Istanbul, 34030, Turkey (Türkiye)
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Istanbul, 34365, Turkey (Türkiye)
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Karşıyaka, 35575, Turkey (Türkiye)
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London, EC1M 6BQ, United Kingdom
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London, NW1 2PG, United Kingdom
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Manchester, M20 4BX, United Kingdom
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Romford, RM7 0BE, United Kingdom
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Sutton, SM25PT, United Kingdom
Related Publications (7)
Mateo 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.
PMID: 37963304DERIVEDRoubaud 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.
PMID: 35598359DERIVEDMatsubara 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.
PMID: 35229141DERIVEDThiery-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.
PMID: 35157830DERIVEDHussain 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.
PMID: 35091440DERIVEDHussain 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.
PMID: 32955174DERIVEDde 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.
PMID: 32343890DERIVED
Related Links
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Global Clinical Lead
- Organization
- AstraZeneca Clinical Study Information Center
Study Officials
- PRINCIPAL INVESTIGATOR
Johann de Bono, M.D., Ph.D.
The Institute of Cancer Research, United Kingdom
- PRINCIPAL INVESTIGATOR
Maha Hussain, M.D., FACP, FASCO
Northwestern University, United States of America
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 15, 2016
First Posted
December 9, 2016
Study Start
February 6, 2017
Primary Completion
June 4, 2019
Study Completion
February 15, 2023
Last Updated
October 6, 2023
Results First Posted
October 12, 2020
Record last verified: 2023-09