Olaparib Treatment in BRCA Mutated Ovarian Cancer Patients After Complete or Partial Response to Platinum Chemotherapy
- Conditions
- Relapsed Ovarian CancerFollowing Complete or Partial Response to Platinum Based ChemotherapyPlatinum SensitiveBRCA Mutated
- Interventions
- Drug: Olaparib 300mg tabletsDrug: Placebo to match olaparib 300mg
- Registration Number
- NCT01874353
- Lead Sponsor
- AstraZeneca
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- Female
- Target Recruitment
- 327
-
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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Olaparib 300mg tablets Olaparib 300mg tablets Taken orally twice daily Placebo tablets Placebo to match olaparib 300mg Taken orally twice daily
- Primary Outcome Measures
Name Time Method Progression Free Survival (PFS) Using Investigator Assessment According to Modified Response Evaluation Criteria In Solid Tumours (RECIST 1.1) Radiologic scans performed at baseline then every ~12 weeks up to 72 weeks, then every ~ 24 weeks thereafter until objective radiological disease progression. Assessed until 19 Sep 2016 DCO (16 Jan 2017 DCO for China Cohort); up to a maximum of 36 months. To determine the efficacy by progression free survival (PFS) (using investigator assessment according to modified Response Evaluation Criteria In Solid Tumours (RECIST 1.1)) of olaparib maintenance monotherapy compared to placebo in BRCA mutated relapsed ovarian cancer patients who are in complete or partial response following platinum based chemotherapy.
- Secondary Outcome Measures
Name Time Method Efficacy of Olaparib by Time From Randomization to Study Treatment Discontinuation or Death (TDT) Time elapsed from randomization to study treatment discontinuation or death. Assessed until 03 Feb 2020 DCO; up to a maximum of 75 months. To determine the efficacy of olaparib maintenance monotherapy compared to placebo in BRCA mutated high risk advanced ovarian cancer patients who are in clinical complete response or partial response following first line platinum based chemotherapy by assessment of time from randomization to study treatment discontinuation or death (TDT).
Efficacy in Patients Following Platinum Based Chemotherapy by Assessment of Time to Earliest Progression by RECIST or Cancer Antigen (CA-125) or Death CA-125 at baseline then every 4 wks. Radiologic scans at baseline then every ~12 wks up to 72 wks, then every ~ 24 wks until objective radiological disease progression. Assessed until 19Sep2016 DCO (16Jan2017 DCO for China Cohort); up to a max of 36 mths. To determine the efficacy of olaparib maintenance monotherapy compared to placebo in BRCA mutated relapsed ovarian cancer patients who are in complete or partial response following platinum based chemotherapy by assessment of time to earliest progression by RECIST or CA-125 or death.
Change From Baseline in Health-Related Quality of Life (HRQoL) as Assessed by the the Trial Outcome Index (TOI) of the Functional Assessment of Cancer Therapy - Ovarian (FACT-O) Questionnaires completed by patient at baseline, Day 29 and then every 12 weeks for 12 months. Assessed until 19 Sep 2016 DCO. To compare the effects of olaparib maintenance monotherapy compared to placebo on Health-related Quality of Life (HRQoL) as assessed by the trial outcome index (TOI) of the Functional Assessment of Cancer Therapy - Ovarian (FACT-O) in BRCA mutated relapsed ovarian cancer patients who are in complete or partial response following platinum based chemotherapy. The TOI ranges from 0-100 and a higher score indicates a higher HRQoL.
To Determine the Exposure to Olaparib by Pharmacokinetic Analysis Pharmacokinetics sampling to be performed in a subset of patients. Sampling times: Day 1 pre-dose & 1 hour; Day 15 pre-dose & 1 hour; Day 29 pre-dose. Assessed until 19 Sep 2016 DCO. To determine the exposure to olaparib in patients receiving olaparib maintenance monotherapy
Efficacy in Patients Following Platinum Based Chemotherapy by Assessment of Overall Survival Survival assessed every 4 weeks until treatment discontinues, then every 12 weeks. Assessed until 03 Feb 2020 DCO; up to a maximum of 75 months. To determine the efficacy of olaparib maintenance monotherapy compared to placebo in BRCA mutated relapsed ovarian cancer patients who are in complete or partial response following platinum based chemotherapy by assessment of overall survival (OS).
Efficacy in Patients Following Platinum Based Chemotherapy by Assessment of Time From Randomization to Second Progression Scans at baseline then every 12 wks for 72 wks, then every 24 wks until first progression. Assessments then per local practice every 12 wks until second progression. Assessed until 19Sep2016 DCO (16Jan2017 DCO for China Cohort); up to a max of 36 mths To determine the efficacy of olaparib maintenance monotherapy compared to placebo in BRCA mutated relapsed ovarian cancer patients who are in complete response or partial response following first line platinum based chemotherapy by assessment of time from randomization up to second progression
Efficacy of Olaparib by Time to First Subsequent Therapy or Death (TFST) Time elapsed from randomization to first subsequent therapy or death. Assessed every 12 weeks following treatment discontinuation. Assessed until 03 Feb 2020 DCO; up to a maximum of 75 months. To determine the efficacy of olaparib maintenance monotherapy compared to placebo in BRCA mutated high risk advanced ovarian cancer patients who are in clinical complete response or partial response following first line platinum based chemotherapy by assessment of time from randomization to first subsequent therapy or death (TFST).
Efficacy of Olaparib by Time to Second Subsequent Therapy or Death (TSST) Time elapsed from randomization to second subsequent therapy or death. Assessed every 12 weeks following treatment discontinuation. Assessed until 03 Feb 2020 DCO; up to a maximum of 75 months. To determine the efficacy of olaparib maintenance monotherapy compared to placebo in BRCA mutated high risk advanced ovarian cancer patients who are in clinical complete response or partial response following first line platinum based chemotherapy by assessment of time from randomization to second subsequent therapy or death (TSST).
Efficacy in Patients With a Deleterious or Suspected Deleterious Variant in Either of the BRCA Genes by Assessment of PFS. Radiologic scans performed at baseline then every ~12 weeks for the first 72 weeks, then every ~24 weeks thereafter, assessed until disease progression. Assessed until 19 Sep 2016 DCO. To assess efficacy of olaparib in patients identified as having a deleterious or suspected deleterious variant in either of the BRCA genes using variants identified with current and future BRCA mutation assays (gene sequencing and large rearrangement analysis).
Trial Locations
- Locations (125)
North Shore University
🇺🇸Evanston, Illinois, United States
Sunnybrook Health Sciences Center
🇨🇦Toronto, Ontario, Canada
West China Hospital Affiliated to Sichuan University
🇨🇳Chengdu, 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
The First Affiliated Hospital of Soochow University
🇨🇳Suzhou, China
Helios-Kliniken Berlin - Buch
🇩🇪Berlin, Germany
Institut Claudius Regaud
🇫🇷Toulouse, France
Institut Curie Paris Et Saint Cloud
🇫🇷Paris Cedex 5, France
Johann-Wolfgang Goethe-Universität
🇩🇪Frankfurt, Germany
Universitätsklinikum Schleswig-Holstein
🇩🇪Lübeck, Germany
Medizinische Hochschule Hannover
🇩🇪Hannover, Germany
Universitätsklinikum Rostock
🇩🇪Rostock, Germany
Sapir Medical Centre
🇮🇱Kfar Saba, Israel
Azienda Ospedaliera Policlinico Di Modena
🇮🇹Modena, Italy
Onkologie Ravensburg
🇩🇪Ravensburg, Germany
Istituto Europeo di Oncologia
🇮🇹Milano, Italy
Istituto Oncologico Veneto Irccs
🇮🇹Padova, Italy
Hyogo Cancer Center
🇯🇵Akashi-shi, Japan
National Cancer Center Hospital
🇯🇵Chuo-ku, Japan
Niigata University Medical and Dental Hospital
🇯🇵Niigata-shi, Japan
Gangnam Severance Hospital
🇰🇷Seoul, Korea, Republic of
Shizuoka Cancer Center
🇯🇵Sunto-gun, Japan
The Christie NHS Foundation Trust
🇬🇧Manchester, United Kingdom
Winthrop Gynecologic Oncology Associates
🇺🇸Mineola, New York, United States
Womens Cancer Care Associates
🇺🇸Albany, New York, United States
Mercy Hospital for Women
🇦🇺Heidelberg, Australia
Niepubliczny Zaklad Opieki Zdrowotnej Innowacyjna Medycyna
🇵🇱Grzepnica, Poland
Women's Hospital, Zhejaing University School of Medicine
🇨🇳Hangzhou, China
CAC François Baclesse
🇫🇷Caen Cedex, France
Hunan Cancer Hospital
🇨🇳Changsha, China
Centro Regional Integrado de Oncologia
🇧🇷Fortaleza, Brazil
Instituto do Câncer de São Paulo
🇧🇷São Paulo, Brazil
OSU JamesCare at Mill Run
🇺🇸Hilliard, Ohio, United States
CHUM - Hopital Norte-Dame
🇨🇦Montreal, Quebec, Canada
Princess Margaret Cancer Centre
🇨🇦Toronto, Ontario, Canada
National Hospital Organization Kyushu Cancer Center
🇯🇵Fukuoka, Japan
Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital
🇳🇱Amsterdam, Netherlands
Research Site
🇨🇳Shanghai, China
The Royal Womens Hospital
🇦🇺Parkville, Australia
75PARIS, H Tenon, Onco
🇫🇷Paris, France
Hopital Européen Georges Pompidou
🇫🇷Paris, France
Universitair Medisch Centrum St. Radboud
🇳🇱Nijmegen, Netherlands
Erasmus Medisch Centrum
🇳🇱Rotterdam, Netherlands
Istituto Nazionale Tumori Fondazione Pascale
🇮🇹Napoli, Italy
CHUS Site Fleurimont
🇨🇦Sherbrooke, Quebec, Canada
The Tumour Hospital of Harbin Medical University
🇨🇳Harbin, China
Centre Alexis Vautrin
🇫🇷Vandoeuvre Les Nancy, France
Edinburgh Cancer Research UK Centre
🇬🇧Edinburgh, United Kingdom
Barcelona,H.de la Sta.Creu i S.Pau,Oncología
🇪🇸Barcelona, Spain
Madrid,H.12 de Octubre,Oncología
🇪🇸Madrid, Spain
Arden Cancer Centre
🇬🇧Coventry, United Kingdom
Royal Marsden Hospital and Institute of Cancer Research
🇬🇧Sutton, United Kingdom
Hospital Provincial de Navarra
🇪🇸Pamplona, Spain
SPZOZ MSWiA z Warminsko-Mazurskim Centrum Onkologii
🇵🇱Olsztyn, Poland
City Hospital Birmingham Cancer Trials Team
🇬🇧Birmingham, United Kingdom
Royal Marsden Hospital
🇬🇧London, United Kingdom
Centrum Onkologii Instytut im Marii Sklodowskiej-Curie
🇵🇱Warszawa, Poland
Szpital Specjalistyczny im. Swietej Rodziny SPZOZ
🇵🇱Warszawa, Poland
Valencia, IVO, Oncología
🇪🇸Valencia, Spain
Madrid, H.C.S.Carlos,Oncología
🇪🇸Madrid, Spain
Addenbrooke's Hospital
🇬🇧Cambridge, United Kingdom
Gerona,H.Josep Trueta,Oncología
🇪🇸Gerona, Spain
Valencia,H.C.U.Valencia,Oncología
🇪🇸Valencia, Spain
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Prince of Wales Hospital
🇦🇺Randwick, Australia
Hospital de Base São José do Rio Preto
🇧🇷São José do Rio Preto, Brazil
London Health Sciences Centre
🇨🇦London, Ontario, Canada
JINAN, Qi Lu Hosp. of SD Univ.
🇨🇳Ji Nan, China
Zhejiang Cancer Hospital, Huangzhou
🇨🇳Huangzhou, China
Shanghai Cancer Hospital of Fudan University
🇨🇳Shanghai, China
69LYON, C Bérard, Onco
🇫🇷Lyon Cedex 08, France
69PIERREBE, CH Lyon Sud,
🇫🇷Pierre Benite Cedex, France
Klinikum rechts der Isar der Technischen Universität
🇩🇪München, Germany
National Hospital Organization Shikoku Cancer Center
🇯🇵Matsuyama-shi, Japan
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Córdoba,H.Reina Sofía,Oncología
🇪🇸Córdoba, Spain
Barcelona,H.Clinic i Provincial,Oncología
🇪🇸Barcelona, Spain
St.Petersburg City Oncology Dispensary, Dept. Gynecology
🇷🇺Saint Petersburg, Russian Federation
Cancer Research UK and UCL Cancer Trials Centre
🇬🇧London, United Kingdom
Hotel-Dieu de Quebec
🇨🇦Quebec, Canada
Hospital Araujo Jorge
🇧🇷Goiânia, Brazil
Irmandade da Santa Casa de Misericordia de Porto Alagre
🇧🇷Porto Alegre, Brazil
ChongQing Cancer Hospital
🇨🇳Chongqing, China
Institut Bergonie
🇫🇷Bordeaux, France
Centre Catherine de Sienne
🇫🇷Nantes,, France
92STCLOUD, C Huguenin, Onco
🇫🇷Saint Cloud, France
Institut Gustave Roussy
🇫🇷Villejuif Cedex, France
Friedrich-Alexander-Universität Erlangen-Nürnberg
🇩🇪Erlangen, Germany
Klinikum Essen-Mitte,Evang. Huyssens-Stiftung/Knapps gGmbH
🇩🇪Essen, Germany
Rambam Health Care Campus
🇮🇱Haifa, Israel
Tel Hashomer
🇮🇱Ramat Gan, Israel
Maastricht Universitair Medisch Centrum
🇳🇱Maastricht, Netherlands
MD Anderson at Cooper Cancer Center
🇺🇸Voorhees, New Jersey, United States
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Beijing Cancer Hospital
🇨🇳Beijing, China
Istituto Regina Elena-Polo Oncologico Ifo
🇮🇹Roma, Italy
The Hospital of Central Connecticut
🇺🇸New Britain, Connecticut, United States
Greater Baltimore Medical Center
🇺🇸Baltimore, Maryland, United States
Johns Hopkins
🇺🇸Baltimore, Maryland, United States
U.Z. Gent
🇧🇪Gent, Belgium
UZ Leuven Gasthuisberg
🇧🇪Leuven, Belgium
Centro Diagnóstico Barretos
🇧🇷Barretos, Brazil
Centro de Referencia da Saude da Mulher
🇧🇷São Paulo, Brazil
Centro de Novos Tratamentos Itajai
🇧🇷Itajai, Brazil
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Hospital de Caridade de Ijuí
🇧🇷Ijuí, Brazil
Hospital de Clinicas de Porto Alegre
🇧🇷Porto Alegre, Brazil
Juravinski Cancer Centre
🇨🇦Hamilton, Ontario, Canada
First affiliated hospital college of XianJiaotong University
🇨🇳Xian, China
Policlinico Universitario A. Gemelli
🇮🇹Roma, Italy
Kindai University Hospital
🇯🇵Osakasayama-shi, Japan
Leningrad Regional Oncology Dispensary
🇷🇺St.Petersburg, Russian Federation
Saitama Medical University International Medical Center
🇯🇵Hidaka-shi, Japan
Hokkaido University Hospital
🇯🇵Sapporo-shi, Japan
Wojewódzki Szpital Specjalistyczny w Olsztynie
🇵🇱Olsztyn, Poland
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
Gynecologic Cancer Center
🇺🇸Orlando, Florida, United States
Henry Joyce Cancer Clinic
🇺🇸Nashville, Tennessee, United States
Aurora St Lukes Medical Center
🇺🇸Milwaukee, Wisconsin, United States
Chemotherapy Department, Russian Cancer Research Centre
🇷🇺Moscow, Russian Federation