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

Relapsed Ovarian Cancer Clinical Trial

Official title:

Phase III Randomised, Double Blind, Placebo Controlled Study of Olaparib Maintenance Monotherapy in Platinum Sensitive Relapsed BRCA Mutated Ovarian Cancer Patients With a Complete or Partial Response Following Platinum Based Chemotherapy

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01874353
• Other study ID #: D0816C00002
• Secondary ID: 2013-001211-75
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: September 3, 2013
• Est. completion date: December 31, 2024

Study information

• Verified date: March 2024
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 327
• Est. completion date: December 31, 2024
• Est. primary completion date: September 19, 2016
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 130 Years

Eligibility

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.

Related Conditions & MeSH terms

• BRCA Mutated
• Carcinoma, Ovarian Epithelial
• Following Complete or Partial Response to Platinum Based Chemotherapy
• Hypersensitivity
• Ovarian Neoplasms
• Platinum Sensitive
• Relapsed Ovarian Cancer

Intervention

Drug:
• 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.
• 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.

Locations

Country	Name	City	State
Australia	Mercy Hospital for Women	Heidelberg
Australia	The Royal Womens Hospital	Parkville
Australia	Prince of Wales Hospital	Randwick
Belgium	U.Z. Gent	Gent
Belgium	UZ Leuven Gasthuisberg	Leuven
Brazil	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	Itajai
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
Canada	Juravinski Cancer Centre	Hamilton	Ontario
Canada	London Health Sciences Centre	London	Ontario
Canada	CHUM - Hopital Norte-Dame	Montreal	Quebec
Canada	Hotel-Dieu de Quebec	Quebec
Canada	CHUS Site Fleurimont	Sherbrooke	Quebec
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
Canada	Sunnybrook Health Sciences Center	Toronto	Ontario
China	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.	Ji Nan
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	Xian
France	Institut Bergonie	Bordeaux
France	CAC François Baclesse	Caen Cedex
France	69LYON, C Bérard, Onco	Lyon Cedex 08
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 Cedex 5
France	69PIERREBE, CH Lyon Sud,	Pierre Benite Cedex
France	92STCLOUD, C Huguenin, Onco	Saint Cloud
France	Institut Claudius Regaud	Toulouse
France	Centre Alexis Vautrin	Vandoeuvre Les Nancy
France	Institut Gustave Roussy	Villejuif Cedex
Germany	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	Hannover
Germany	Universitätsklinikum Schleswig-Holstein	Lübeck
Germany	Klinikum rechts der Isar der Technischen Universität	München
Germany	Onkologie Ravensburg	Ravensburg
Germany	Universitätsklinikum Rostock	Rostock
Israel	Rambam Health Care Campus	Haifa
Israel	Sapir Medical Centre	Kfar Saba
Israel	Tel Hashomer	Ramat Gan
Italy	Istituto Europeo di Oncologia	Milano
Italy	Azienda Ospedaliera Policlinico Di Modena	Modena
Italy	Istituto Nazionale Tumori Fondazione Pascale	Napoli
Italy	Istituto Oncologico Veneto Irccs	Padova
Italy	Istituto Regina Elena-Polo Oncologico Ifo	Roma
Italy	Policlinico Universitario A. Gemelli	Roma
Japan	Hyogo Cancer Center	Akashi-shi
Japan	National Cancer Center Hospital	Chuo-ku
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-shi
Japan	Niigata University Medical and Dental Hospital	Niigata-shi
Japan	Kindai University Hospital	Osakasayama-shi
Japan	Hokkaido University Hospital	Sapporo-shi
Japan	Shizuoka Cancer Center	Sunto-gun
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Gangnam Severance Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Netherlands	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
Poland	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	Warszawa
Poland	Szpital Specjalistyczny im. Swietej Rodziny SPZOZ	Warszawa
Russian Federation	Chemotherapy Department, Russian Cancer Research Centre	Moscow
Russian Federation	St.Petersburg City Oncology Dispensary, Dept. Gynecology	Saint Petersburg
Russian Federation	Leningrad Regional Oncology Dispensary	St.Petersburg
Spain	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	Gerona
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
United Kingdom	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 States	Womens Cancer Care Associates	Albany	New York
United States	University of Colorado	Aurora	Colorado
United States	Greater Baltimore Medical Center	Baltimore	Maryland
United States	Johns Hopkins	Baltimore	Maryland
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	North Shore University	Evanston	Illinois
United States	OSU JamesCare at Mill Run	Hilliard	Ohio
United States	Aurora St Lukes Medical Center	Milwaukee	Wisconsin
United States	Winthrop Gynecologic Oncology Associates	Mineola	New York
United States	Henry Joyce Cancer Clinic	Nashville	Tennessee
United States	The Hospital of Central Connecticut	New Britain	Connecticut
United States	Gynecologic Cancer Center	Orlando	Florida
United States	Palo Alto Foundation Medical Group	San Francisco	California
United States	MD Anderson at Cooper Cancer Center	Voorhees	New Jersey

Sponsors (4)

Lead Sponsor	Collaborator
AstraZeneca	European Network of Gynaecological Oncological Trial Groups (ENGOT), Merck Sharp & Dohme LLC, Myriad Genetic Laboratories, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Brazil,  Canada,  China,  France,  Germany,  Israel,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Poland,  Russian Federation,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival (PFS) Using Investigator Assessment According to Modified Response Evaluation Criteria In Solid Tumours (RECIST 1.1)	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.	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.
Secondary	Efficacy in Patients Following Platinum Based Chemotherapy by Assessment of Overall Survival	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).	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.
Secondary	Efficacy in Patients Following Platinum Based Chemotherapy by Assessment of Time to Earliest Progression by RECIST or Cancer Antigen (CA-125) or Death	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.	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.
Secondary	Efficacy in Patients Following Platinum Based Chemotherapy by Assessment of Time From Randomization to Second Progression	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	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
Secondary	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)	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.	Questionnaires completed by patient at baseline, Day 29 and then every 12 weeks for 12 months. Assessed until 19 Sep 2016 DCO.
Secondary	Efficacy of Olaparib by Time to First Subsequent Therapy or Death (TFST)	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).	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.
Secondary	Efficacy of Olaparib by Time to Second Subsequent Therapy or Death (TSST)	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).	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.
Secondary	Efficacy of Olaparib by Time From Randomization to Study Treatment Discontinuation or Death (TDT)	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).	Time elapsed from randomization to study treatment discontinuation or death. Assessed until 03 Feb 2020 DCO; up to a maximum of 75 months.
Secondary	Efficacy in Patients With a Deleterious or Suspected Deleterious Variant in Either of the BRCA Genes by Assessment of PFS.	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).	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.
Secondary	To Determine the Exposure to Olaparib by Pharmacokinetic Analysis	To determine the exposure to olaparib in patients receiving olaparib maintenance monotherapy	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.

External Links

•   Redacted CSR synopsis