Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study of Olaparib (Lynparza™) Versus Enzalutamide or Abiraterone Acetate in Men With Metastatic Castration-Resistant Prostate Cancer (PROfound Study)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02987543
Recruitment Status : Active, not recruiting
First Posted : December 9, 2016
Last Update Posted : June 12, 2019
Sponsor:
Collaborators:
Merck Sharp & Dohme Corp.
Foundation Medicine, Inc.
Myriad Genetics, Inc.
Information provided by (Responsible Party):
AstraZeneca

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.

Condition or disease Intervention/treatment Phase
Metastatic Castration-resistant Prostate Cancer Drug: olaparib Drug: enzalutamide Drug: abiraterone acetate Phase 3

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.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 340 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : February 6, 2017
Actual Primary Completion Date : June 4, 2019
Estimated Study Completion Date : February 5, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arm Intervention/treatment
Experimental: Olaparib
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
Drug: olaparib
300 mg (2x 150 mg tablets) twice daily
Other Name: Lynparza

Active Comparator: Enzalutamide OR abiraterone acetate

Enzalutamide:

Enzalutamide is available as capsules 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.

Drug: enzalutamide
160 mg (4 x 40 mg capsules) once daily
Other Name: XTANDI

Drug: abiraterone acetate
1,000 mg (4 x 250 mg tablets) once daily
Other Name: ZYTIGA

Drug: abiraterone acetate
1,000 mg (2 x 500 mg tablets) once daily
Other Name: ZYTIGA




Primary Outcome Measures :
  1. Change in radiographic progression free survival (rPFS) [ Time Frame: During study period (up to 3 years) ]
    rPFS in subjects with BRCA1, BRCA2, or ATM qualifying gene mutations defined as the time from randomization to radiographic progression by blinded independent central reader (BICR) using RECIST 1.1 (soft tissue) and PCWG3 (bone) criteria or death.


Secondary Outcome Measures :
  1. Confirmed Objective Response Rate (ORR) by BICR [ Time Frame: During study period (up to 3 years) ]
    Confirmed ORR by BICR in subjects with measurable disease using RECIST 1.1 (soft tissue) and PCWG3 (bone) criteria

  2. Time to Pain progression [ Time Frame: To be completed by subject daily for 7 consecutive days before each respective 4-week visit/assessment date with Day 1 as the baseline visit date (not required to be at site) ]
    Time to pain progression defined as the time from randomization to increase in pain based on brief pain inventory (short form) question #3 and opioid analgesic usage

  3. Overall Survival (OS) [ Time Frame: During study period (up to 4 years) ]
    OS defined as time from randomization to death due to any cause

  4. rPFS [ Time Frame: During study period (up to 3 years) ]
    rPFS in subjects with HRR qualifying mutations defined as the time from randomization to radiographic progression by blinded independent central reader (BICR) using RECIST 1.1 (soft tissue) and PCWG3 (bone) criteria or death

  5. AEs/SAEs and Collection of clinical chemistry/hematology parameters [ Time Frame: From the time of signature of informed consent throughout the treatment period up to and including the 30-day follow-up period. ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria

  1. Histologically confirmed diagnosis of prostate cancer.
  2. Documented evidence of metastatic castration resistant prostate cancer (mCRPC).
  3. 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 .
  4. Ongoing therapy with LHRH analog or bilateral orchiectomy.
  5. Radiographic progression at study entry while on androgen deprivation therapy (or after bilateral orchiectomy).
  6. Qualifying HRR mutation in tumor tissue.

Exclusion criteria

  1. Any previous treatment with PARP inhibitor, including olaparib.
  2. 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.
  3. 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.
  4. Subjects with known brain metastases.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02987543


  Hide Study Locations
Locations
Layout table for location information
United States, Alaska
Research Site
Anchorage, Alaska, United States, 99503
United States, Arizona
Research Site
Tucson, Arizona, United States, 85704
Research Site
Tucson, Arizona, United States, 85741
United States, California
Research Site
Duarte, California, United States, 91010
Research Site
San Diego, California, United States, 92161
Research Site
Santa Barbara, California, United States, 93105
United States, District of Columbia
Research Site
Washington, District of Columbia, United States, 20007
United States, Florida
Research Site
Tampa, Florida, United States, 33612
United States, Georgia
Research Site
Atlanta, Georgia, United States, 30318
United States, Illinois
Research Site
Chicago, Illinois, United States, 60611
United States, Indiana
Research Site
Jeffersonville, Indiana, United States, 47130
United States, Louisiana
Research Site
New Orleans, Louisiana, United States, 70112
United States, Maryland
Research Site
Baltimore, Maryland, United States, 21287
Research Site
Towson, Maryland, United States, 21204
United States, Nebraska
Research Site
Omaha, Nebraska, United States, 68130
United States, Nevada
Research Site
Las Vegas, Nevada, United States, 89135
United States, New York
Research Site
Albany, New York, United States, 12208
Research Site
Bronx, New York, United States, 10468
Research Site
Brooklyn, New York, United States, 11201
Research Site
Syracuse, New York, United States, 13210
United States, North Carolina
Research Site
Durham, North Carolina, United States, 27710
Research Site
Salisbury, North Carolina, United States, 28144
United States, Ohio
Research Site
Gahanna, Ohio, United States, 43230
United States, Oklahoma
Research Site
Oklahoma City, Oklahoma, United States, 73104
United States, Oregon
Research Site
Springfield, Oregon, United States, 97477
Research Site
Tualatin, Oregon, United States, 97062
United States, South Carolina
Research Site
Charleston, South Carolina, United States, 29401
Research Site
Charleston, South Carolina, United States, 29425
Research Site
Myrtle Beach, South Carolina, United States, 29572
United States, Tennessee
Research Site
Germantown, Tennessee, United States, 38138
Research Site
Nashville, Tennessee, United States, 37232
United States, Texas
Research Site
San Antonio, Texas, United States, 78229
United States, Utah
Research Site
Salt Lake City, Utah, United States, 84112
Research Site
Salt Lake City, Utah, United States, 84148
United States, Washington
Research Site
Spokane, Washington, United States, 99202
United States, West Virginia
Research Site
Wheeling, West Virginia, United States, 26041
Argentina
Research Site
Buenos Aires, Argentina, 1426
Research Site
Buenos Aires, Argentina, C1118AAT
Research Site
Buenos Aires, Argentina, C1120AAT
Research Site
Caba, Argentina, 1280AEB
Research Site
La Rioja, Argentina, 5300
Research Site
Rosario, Argentina
Australia
Research Site
Adelaide, Australia, 5000
Research Site
Box Hill, Australia, 3128
Research Site
Clayton, Australia, 3168
Research Site
Greenslopes, Australia, 4120
Research Site
Herston, Australia, 4029
Research Site
Macquarie University, Australia, 2109
Research Site
Melbourne, Australia, 3000
Research Site
Nedlands, Australia, 6009
Research Site
Randwick, Australia, 2031
Research Site
Waratah, Australia, 2298
Austria
Research Site
Graz, Austria, 8036
Research Site
Linz, Austria, 4020
Research Site
Salzburg, Austria, 5020
Research Site
Wien, Austria, 1020
Research Site
Wien, Austria, 1090
Brazil
Research Site
Barretos, Brazil, 14784-400
Research Site
Belo Horizonte, Brazil, 30110-022
Research Site
Curitiba, Brazil, 80530-010
Research Site
Florianópolis, Brazil, 88034-000
Research Site
Passo Fundo, Brazil, 99010-080
Research Site
Porto Alegre, Brazil, 90160-093
Research Site
Porto Alegre, Brazil, 90610-000
Research Site
Recife, Brazil, 50040-000
Research Site
Ribeirao Preto, Brazil, 14015-140
Research Site
Rio de Janeiro, Brazil, 22793-080
Research Site
Santo Andre, Brazil, 09060-650
Research Site
São José do Rio Preto, Brazil, 15090-000
Research Site
São Paulo, Brazil, 01321-001
Research Site
São Paulo, Brazil, 03102-006
Canada, Alberta
Research Site
Edmonton, Alberta, Canada, T6G 1Z2
Canada, British Columbia
Research Site
Kelowna, British Columbia, Canada, V1Y 5L3
Research Site
Vancouver, British Columbia, Canada, V5Z 4E6
Canada, Ontario
Research Site
Hamilton, Ontario, Canada, L8V 5C2
Research Site
Oakville, Ontario, Canada, L6H 3P1
Research Site
Toronto, Ontario, Canada, M4N 3M5
Research Site
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
Research Site
Chicoutimi, Quebec, Canada, G7H 5H6
Research Site
Montreal, Quebec, Canada, H2X 3E4
Research Site
Montreal, Quebec, Canada, H4A 3J1
Canada, Saskatchewan
Research Site
Saskatoon, Saskatchewan, Canada, S7N 4H4
Canada
Research Site
Quebec, Canada, G1R 2J6
China
Research Site
Beijing, China, 100034
Research Site
Beijing, China, 100039
Research Site
Beijing, China, 100050
Research Site
Beijing, China, 100191
Research Site
Beijing, China, 100730
Research Site
Changsha, China, 410008
Research Site
Changsha, China, 410013
Research Site
Chengdu, China, 610041
Research Site
Chongqing, China, 400010
Research Site
ChongQing, China, 400038
Research Site
Guang Zhou, China, 510080
Research Site
Hangzhou, China, 310009
Research Site
Hangzhou, China, 310014
Research Site
Nanjing, China, 210008
Research Site
Shanghai, China, 200040
Research Site
Shanghai, China, 200080
Research Site
Shanghai, China, 200127
Research Site
Shanghai, China, 200433
Research Site
Shanghai, China, CN-200092
Research Site
Shenyang, China, 110001
Research Site
Suzhou, China, 215004
Research Site
Wuhan, China, CN-430070
Research Site
Xi'an, China, 710061
Research Site
Xiamen, China, 361003
Denmark
Research Site
Odense C, Denmark, 5000
France
Research Site
BESANCON Cedex, France, 25030
Research Site
Bordeaux Cedex, France, 33076
Research Site
Caen, France, 14000
Research Site
Lille, France, 59020
Research Site
Lyon Cedex 08, France, 69373
Research Site
Marseille cedex 09, France, 13273
Research Site
Montpellier, France, 34298
Research Site
Paris, France, 75014
Research Site
Poitiers Cedex, France, 86021
Research Site
Saint Herblain, France, 44805
Research Site
Toulouse Cedex 09, France, 31059
Research Site
Vandoeuvre les Nancy, France, 54519
Research Site
Villejuif, France, 94805
Germany
Research Site
Bergisch Gladbach, Germany, 51465
Research Site
Berlin, Germany, 13055
Research Site
Bremen, Germany, 28277
Research Site
Duisburg, Germany, 47179
Research Site
Düsseldorf, Germany, 40225
Research Site
Hamburg, Germany, 22399
Research Site
Heidelberg, Germany, 69120
Research Site
Holzminden, Germany, 37603
Research Site
Jena, Germany, 07747
Research Site
Köln, Germany, 50968
Research Site
Magdeburg, Germany, 39120
Research Site
Nürnberg, Germany, 90491
Research Site
Nürtingen, Germany, 72766
Research Site
Tübingen, Germany, 72076
Research Site
Wuppertal, Germany, 42109
Israel
Research Site
Haifa, Israel, 31096
Research Site
Jerusalem, Israel, 91120
Research Site
Kfar Saba, Israel, 95847
Research Site
Petach-Tikva, Israel, 4941492
Research Site
Ramat Gan, Israel, 5265601
Research Site
Zerifin, Israel, 70300
Italy
Research Site
Ancona, Italy, 60126
Research Site
Arezzo, Italy, 52100
Research Site
Bari, Italy, 70124
Research Site
Brescia, Italy, 25123
Research Site
Meldola, Italy, 47014
Research Site
Milano, Italy, 20133
Research Site
Milano, Italy, 20141
Research Site
Modena, Italy, 41124
Research Site
Napoli, Italy, 80131
Research Site
Trento, Italy, 38100
Japan
Research Site
Bunkyo-ku, Japan, 113-8431
Research Site
Bunkyo-ku, Japan, 113-8510
Research Site
Bunkyo-ku, Japan, 113-8603
Research Site
Fukuoka, Japan, 812-8582
Research Site
Hirosaki-shi, Japan, 036-8563
Research Site
Kanazawa-shi, Japan, 920-8641
Research Site
Kashihara-shi, Japan, 634-8522
Research Site
Kashiwa, Japan, 277-8577
Research Site
Kawagoe-shi, Japan, 350-8550
Research Site
Kita-gun, Japan, 761-0793
Research Site
Koto-ku, Japan, 135-8550
Research Site
Kyoto-shi, Japan, 606-8507
Research Site
Maebashi-shi, Japan, 371-8811
Research Site
Matsuyama-shi, Japan, 791-0280
Research Site
Minato-ku, Japan, 105-8471
Research Site
Mitaka-shi, Japan, 181-8611
Research Site
Miyazaki-shi, Japan, 889-1692
Research Site
Nagasaki-shi, Japan, 852-8501
Research Site
Nagoya-shi, Japan, 464-8681
Research Site
Nagoya-shi, Japan, 466-8560
Research Site
Osaka-shi, Japan, 541-8567
Research Site
Osaka-shi, Japan, 545-0051
Research Site
Osakasayama-shi, Japan, 589-8511
Research Site
Sagamihara-shi, Japan, 252-0375
Research Site
Sakura-shi, Japan, 285-8741
Research Site
Sapporo-shi, Japan, 060-8648
Research Site
Shinjuku-ku, Japan, 160-8582
Research Site
Suita-shi, Japan, 565-0871
Research Site
Sunto-gun, Japan, 411-8777
Research Site
Yokohama-shi, Japan, 232-0024
Korea, Republic of
Research Site
Busan, Korea, Republic of, 49241
Research Site
Daegu, Korea, Republic of, 41404
Research Site
Goyang-si, Korea, Republic of, 10408
Research Site
Gwangju, Korea, Republic of, 61469
Research Site
Seoul, Korea, Republic of, 03722
Research Site
Seoul, Korea, Republic of, 05505
Research Site
Seoul, Korea, Republic of, 06273
Research Site
Seoul, Korea, Republic of, 06351
Research Site
Seoul, Korea, Republic of, 06591
Netherlands
Research Site
Amsterdam, Netherlands, 1066 CX
Research Site
Hilversum, Netherlands, 1213 XZ
Research Site
Leiden, Netherlands, 2333 ZA
Research Site
Nijmegen, Netherlands, 6525 GA
Research Site
Tilburg, Netherlands, 5042 AD
Research Site
Zwolle, Netherlands, 8025 AB
Norway
Research Site
Lørenskog, Norway, N-1478
Spain
Research Site
Barcelona, Spain, 08035
Research Site
Gerona, Spain, 17007
Research Site
Madrid, Spain, 28040
Research Site
Madrid, Spain, 28041
Research Site
Malaga, Spain, 29010
Research Site
Oviedo, Spain, 33011
Research Site
Sevilla, Spain, 41009
Sweden
Research Site
Göteborg, Sweden, 413 45
Research Site
Solna, Sweden, 171 64
Taiwan
Research Site
Changhua City, Taiwan, 50006
Research Site
Kaohsiung, Taiwan, 807
Research Site
Kaohsiung, Taiwan, 833
Research Site
Taichung, Taiwan, 404
Research Site
Taichung, Taiwan, 40705
Research Site
Tainan, Taiwan, 70403
Research Site
Taipei, Taiwan, 10002
Research Site
Taipei, Taiwan, 112
Research Site
Taoyuan City, Taiwan, 333
Turkey
Research Site
Adana, Turkey
Research Site
Ankara, Turkey, 06230
Research Site
Ankara, Turkey, 06340
Research Site
Ankara, Turkey, 06590
Research Site
Edirne, Turkey, 22030
Research Site
Istanbul, Turkey, 34030
Research Site
Istanbul, Turkey, 34365
Research Site
Karsiyaka, Turkey, 35575
United Kingdom
Research Site
London, United Kingdom, EC1M 6BQ
Research Site
London, United Kingdom, NW1 2PG
Research Site
Manchester, United Kingdom, M20 4BX
Research Site
Romford, United Kingdom, RM7 0BE
Research Site
Sutton, United Kingdom, SM25PT
Sponsors and Collaborators
AstraZeneca
Merck Sharp & Dohme Corp.
Foundation Medicine, Inc.
Myriad Genetics, Inc.
Investigators
Layout table for investigator information
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

Layout table for additonal information
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02987543     History of Changes
Other Study ID Numbers: D081DC00007
First Posted: December 9, 2016    Key Record Dates
Last Update Posted: June 12, 2019
Last Verified: June 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by AstraZeneca:
metastatic castration-resistant prostate cancer (mCRPC)
homologous recombination repair (HRR)

Additional relevant MeSH terms:
Layout table for MeSH terms
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Olaparib
Abiraterone Acetate
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Steroid Synthesis Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Cytochrome P-450 Enzyme Inhibitors