Olaparib Treatment in BRCA Mutated Ovarian Cancer Patients After Complete or Partial Response to Platinum Chemotherapy

NCT ID: NCT01874353

Last Updated: 2025-08-03

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 327 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-09-03
• Study Completion Date: 2025-12-31

Brief Summary

A Phase III, randomised, double-blind, placebo-controlled, multi-centre study to assess the efficacy of olaparib maintenance monotherapy in relapsed high grade serous ovarian cancer (HGSOC) patients (including patients with primary peritoneal and / or fallopian tube cancer) or high grade endometrioid cancer with BRCA mutations (documented mutation in BRCA1 or BRCA2 that is predicted to be deleterious or suspected deleterious (known or predicted to be detrimental/lead to loss of function)) who have responded following platinum based chemotherapy.

Detailed Description

Comparison of olaparib against a placebo in patients with ovarian cancer whose cancer has already improved by taking platinum based chemotherapy. The patients must also have a fault in their DNA which codes for the BRCA protein. The BRCA protein helps mend broken DNA in the cells of the body; if this protein doesn't work properly it can increase the chance of getting cancer. The aim of this study is to see whether patients taking olaparib tablets last longer until their cancer gets worse, compared to those taking the placebo tablet. The study is also looking to see if there is an overall improvement to how long the patients survive whilst taking olaparib tablets compared to the placebo tablets; and the quality of their life whilst living with ovarian cancer.

Conditions

Platinum Sensitive; BRCA Mutated; Relapsed Ovarian Cancer; Following Complete or Partial Response to Platinum Based Chemotherapy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Olaparib 300mg tablets

Taken orally twice daily

Group Type: EXPERIMENTAL

Olaparib 300mg tablets

Intervention Type: DRUG

300mg Olaparib or placebo tablets taken orally twice daily until objective radiological disease progression as per RECIST as assessed by the investigator (or as long as in the investigator's opinion they are benefiting from treatment and they do not meet any other discontinuation criteria). Dose reduction to 250mg and subsequently 200mg is permitted following confirmation of toxicity.

Placebo tablets

Taken orally twice daily

Group Type: PLACEBO_COMPARATOR

Placebo to match olaparib 300mg

Intervention Type: DRUG

300mg Olaparib or placebo tablets taken orally twice daily until objective radiological disease progression as per RECIST as assessed by the investigator (or as long as in the investigator's opinion they are benefiting from treatment and they do not meet any other discontinuation criteria). Dose reduction to 250mg and subsequently 200mg is permitted following confirmation of toxicity.

Interventions

Olaparib 300mg tablets

300mg Olaparib or placebo tablets taken orally twice daily until objective radiological disease progression as per RECIST as assessed by the investigator (or as long as in the investigator's opinion they are benefiting from treatment and they do not meet any other discontinuation criteria). Dose reduction to 250mg and subsequently 200mg is permitted following confirmation of toxicity.

Intervention Type: DRUG

Placebo to match olaparib 300mg

300mg Olaparib or placebo tablets taken orally twice daily until objective radiological disease progression as per RECIST as assessed by the investigator (or as long as in the investigator's opinion they are benefiting from treatment and they do not meet any other discontinuation criteria). Dose reduction to 250mg and subsequently 200mg is permitted following confirmation of toxicity.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Patients must be ≥ 18 years of age.

• Female patients with histologically diagnosed relapsed high grade serous ovarian cancer (including primary peritoneal and / or fallopian tube cancer) or high grade endometrioid cancer.
• Documented mutation in BRCA1 or BRCA2 that is predicted to be deleterious or suspected deleterious (known or predicted to be detrimental/lead to loss of function).
• Patients who have received at least 2 previous lines of platinum containing therapy prior to randomisation

For the penultimate chemotherapy course prior to enrolment on the study:

• Patient defined as platinum sensitive after this treatment; defined as disease progression greater than 6 months after completion of their last dose of platinum chemotherapy

For the last chemotherapy course immediately prior to randomisation on the study:

• Patients must be, in the opinion of the investigator, in response (partial or complete radiological response), or may have no evidence of disease (if optimal cytoreductive surgery was conducted prior to chemotherapy), and no evidence of a rising CA-125, following completion of this chemotherapy course
• Patient must have received a platinum based chemotherapy regimen (e.g. carboplatin or cisplatin) and have received at least 4 cycles of treatment
• Patients must be randomized within 8 weeks of their last dose of chemotherapy
• Maintenance treatment is allowed at the end of the penultimate platinum regimen, including bevacizumab

Exclusion Criteria

• Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
• BRCA 1 and/or BRCA2 mutations that are considered to be non detrimental (e.g., "Variants of uncertain clinical significance" or "Variant of unknown significance" or "Variant, favor polymorphism" or "benign polymorphism" etc.)
• Patients who have had drainage of their ascites during the final 2 cycles of their last chemotherapy regimen prior to enrolment on the study.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 130 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

European Network of Gynaecological Oncological Trial Groups (ENGOT)

OTHER

Sponsor Role: collaborator

Myriad Genetic Laboratories, Inc.

INDUSTRY

Sponsor Role: collaborator

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

AstraZeneca

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Professor E Pujade-Lauraine, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Universite de Paris Descartes, France

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

Palo Alto Foundation Medical Group

San Francisco, California, United States

University of Colorado

Aurora, Colorado, United States

The Hospital of Central Connecticut

New Britain, Connecticut, United States

Gynecologic Cancer Center

Orlando, Florida, United States

North Shore University

Evanston, Illinois, United States

Greater Baltimore Medical Center

Baltimore, Maryland, United States

Johns Hopkins

Baltimore, Maryland, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

MD Anderson at Cooper Cancer Center

Voorhees Township, New Jersey, United States

Womens Cancer Care Associates

Albany, New York, United States

Winthrop Gynecologic Oncology Associates

Mineola, New York, United States

OSU JamesCare at Mill Run

Hilliard, Ohio, United States

Henry Joyce Cancer Clinic

Nashville, Tennessee, United States

Aurora St Lukes Medical Center

Milwaukee, Wisconsin, United States

Mercy Hospital for Women

Heidelberg, , Australia

The Royal Womens Hospital

Parkville, , Australia

Prince of Wales Hospital

Randwick, , Australia

U.Z. Gent

Ghent, , Belgium

UZ Leuven Gasthuisberg

Leuven, , Belgium

Centro Diagnóstico Barretos

Barretos, , Brazil

Centro Regional Integrado de Oncologia

Fortaleza, , Brazil

Hospital Araujo Jorge

Goiânia, , Brazil

Hospital de Caridade de Ijuí

Ijuí, , Brazil

Centro de Novos Tratamentos Itajai

Itajaí, , Brazil

Hospital de Clinicas de Porto Alegre

Porto Alegre, , Brazil

Irmandade da Santa Casa de Misericordia de Porto Alagre

Porto Alegre, , Brazil

Hospital de Base São José do Rio Preto

São José do Rio Preto, , Brazil

Centro de Referencia da Saude da Mulher

São Paulo, , Brazil

Instituto do Câncer de São Paulo

São Paulo, , Brazil

Juravinski Cancer Centre

Hamilton, Ontario, Canada

London Health Sciences Centre

London, Ontario, Canada

Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Sunnybrook Health Sciences Center

Toronto, Ontario, Canada

CHUM - Hopital Norte-Dame

Montreal, Quebec, Canada

Hotel-Dieu de Quebec

Québec, Quebec, Canada

CHUS Site Fleurimont

Sherbrooke, Quebec, Canada

Beijing Cancer Hospital

Beijing, , China

The Tumor Hospital affiliated to China Medical Science Insti

Beijing, , China

1st Hospital of Jilin university

Changchun, , China

Jilin Provincial Cancer Hospital

Changchun, , China

Hunan Cancer Hospital

Changsha, , China

West China Hospital Affiliated to Sichuan University

Chengdu, , China

ChongQing Cancer Hospital

Chongqing, , China

Research Site

Guangzhou, , China

Women's Hospital, Zhejaing University School of Medicine

Hangzhou, , China

The Tumour Hospital of Harbin Medical University

Harbin, , China

Zhejiang Cancer Hospital, Huangzhou

Huangzhou, , China

JINAN, Qi Lu Hosp. of SD Univ.

Jinan, , China

Research Site

Shanghai, , China

Shanghai Cancer Hospital of Fudan University

Shanghai, , China

The First Affiliated Hospital of Soochow University

Suzhou, , China

First affiliated hospital college of XianJiaotong University

Xi'an, , China

Institut Bergonie

Bordeaux, , France

CAC François Baclesse

Caen, , France

69LYON, C Bérard, Onco

Lyon, , France

Centre Catherine de Sienne

Nantes, , France

75PARIS, H Tenon, Onco

Paris, , France

Hopital Européen Georges Pompidou

Paris, , France

Institut Curie Paris Et Saint Cloud

Paris, , France

69PIERREBE, CH Lyon Sud,

Pierre-Bénite, , France

92STCLOUD, C Huguenin, Onco

Saint-Cloud, , France

Institut Claudius Regaud

Toulouse, , France

Centre Alexis Vautrin

Vandœuvre-lès-Nancy, , France

Institut Gustave Roussy

Villejuif, , France

Helios-Kliniken Berlin - Buch

Berlin, , Germany

Friedrich-Alexander-Universität Erlangen-Nürnberg

Erlangen, , Germany

Klinikum Essen-Mitte,Evang. Huyssens-Stiftung/Knapps gGmbH

Essen, , Germany

Johann-Wolfgang Goethe-Universität

Frankfurt, , Germany

Medizinische Hochschule Hannover

Hanover, , Germany

Universitätsklinikum Schleswig-Holstein

Lübeck, , Germany

Klinikum rechts der Isar der Technischen Universität

München, , Germany

Onkologie Ravensburg

Ravensburg, , Germany

Universitätsklinikum Rostock

Rostock, , Germany

Rambam Health Care Campus

Haifa, , Israel

Sapir Medical Centre

Kfar Saba, , Israel

Tel Hashomer

Ramat Gan, , Israel

Istituto Europeo di Oncologia

Milan, , Italy

Azienda Ospedaliera Policlinico Di Modena

Modena, , Italy

Istituto Nazionale Tumori Fondazione Pascale

Napoli, , Italy

Istituto Oncologico Veneto Irccs

Padua, , Italy

Istituto Regina Elena-Polo Oncologico Ifo

Roma, , Italy

Policlinico Universitario A. Gemelli

Roma, , Italy

Hyogo Cancer Center

Akashi-shi, , Japan

National Cancer Center Hospital

Chūōku, , Japan

National Hospital Organization Kyushu Cancer Center

Fukuoka, , Japan

Saitama Medical University International Medical Center

Hidaka-shi, , Japan

National Hospital Organization Shikoku Cancer Center

Matsuyama, , Japan

Niigata University Medical and Dental Hospital

Niigata, , Japan

Kindai University Hospital

Osakasayama-shi, , Japan

Hokkaido University Hospital

Sapporo, , Japan

Shizuoka Cancer Center

Sunto-gun, , Japan

Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital

Amsterdam, , Netherlands

Maastricht Universitair Medisch Centrum

Maastricht, , Netherlands

Universitair Medisch Centrum St. Radboud

Nijmegen, , Netherlands

Erasmus Medisch Centrum

Rotterdam, , Netherlands

Niepubliczny Zaklad Opieki Zdrowotnej Innowacyjna Medycyna

Grzepnica, , Poland

SPZOZ MSWiA z Warminsko-Mazurskim Centrum Onkologii

Olsztyn, , Poland

Wojewódzki Szpital Specjalistyczny w Olsztynie

Olsztyn, , Poland

Centrum Onkologii Instytut im Marii Sklodowskiej-Curie

Warsaw, , Poland

Szpital Specjalistyczny im. Swietej Rodziny SPZOZ

Warsaw, , Poland

Chemotherapy Department, Russian Cancer Research Centre

Moscow, , Russia

Leningrad Regional Oncology Dispensary

Saint Petersburg, , Russia

St.Petersburg City Oncology Dispensary, Dept. Gynecology

Saint Petersburg, , Russia

Asan Medical Center

Seoul, , South Korea

Gangnam Severance Hospital

Seoul, , South Korea

Samsung Medical Center

Seoul, , South Korea

Seoul National University Hospital

Seoul, , South Korea

Barcelona,H.Clinic i Provincial,Oncología

Barcelona, , Spain

Barcelona,H.de la Sta.Creu i S.Pau,Oncología

Barcelona, , Spain

Córdoba,H.Reina Sofía,Oncología

Córdoba, , Spain

Gerona,H.Josep Trueta,Oncología

Girona, , Spain

Madrid, H.C.S.Carlos,Oncología

Madrid, , Spain

Madrid,H.12 de Octubre,Oncología

Madrid, , Spain

Hospital Provincial de Navarra

Pamplona, , Spain

Valencia, IVO, Oncología

Valencia, , Spain

Valencia,H.C.U.Valencia,Oncología

Valencia, , Spain

City Hospital Birmingham Cancer Trials Team

Birmingham, , United Kingdom

Addenbrooke's Hospital

Cambridge, , United Kingdom

Arden Cancer Centre

Coventry, , United Kingdom

Edinburgh Cancer Research UK Centre

Edinburgh, , United Kingdom

Cancer Research UK and UCL Cancer Trials Centre

London, , United Kingdom

Royal Marsden Hospital

London, , United Kingdom

The Christie NHS Foundation Trust

Manchester, , United Kingdom

Royal Marsden Hospital and Institute of Cancer Research

Sutton, , United Kingdom

Countries

United States; Australia; Belgium; Brazil; Canada; China; France; Germany; Israel; Italy; Japan; Netherlands; Poland; Russia; South Korea; Spain; United Kingdom

References

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Related Links

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Redacted CSR synopsis

Other Identifiers

2013-001211-75

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

D0816C00002

Identifier Type: -

Identifier Source: org_study_id