Trial Review

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 endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01874353




Registration number
NCT01874353
Ethics application status
Date submitted
7/06/2013
Date registered
11/06/2013
Date last updated
25/06/2024

Titles & IDs
Public title
Olaparib Treatment in BRCA Mutated Ovarian Cancer Patients After Complete or Partial Response to Platinum Chemotherapy
Scientific 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
Secondary ID [1] 0 0
2013-001211-75
Secondary ID [2] 0 0
D0816C00002
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Platinum Sensitive 0 0
BRCA Mutated 0 0
Relapsed Ovarian Cancer 0 0
Following Complete or Partial Response to Platinum Based Chemotherapy 0 0
Condition category
Condition code
Cancer 0 0 0 0
Ovarian and primary peritoneal
Inflammatory and Immune System 0 0 0 0
Allergies

Intervention/exposure
Study type
Interventional(has expanded access)
Description of intervention(s) / exposure
Treatment: Drugs - Olaparib 300mg tablets
Treatment: Drugs - Placebo to match olaparib 300mg

Experimental: Olaparib 300mg tablets - Taken orally twice daily

Placebo comparator: Placebo tablets - Taken orally twice daily


Treatment: Drugs: 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.

Treatment: Drugs: 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 code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression Free Survival (PFS) Using Investigator Assessment According to Modified Response Evaluation Criteria In Solid Tumours (RECIST 1.1)
Timepoint [1] 0 0
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 outcome [1] 0 0
Efficacy in Patients Following Platinum Based Chemotherapy by Assessment of Overall Survival
Timepoint [1] 0 0
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 outcome [2] 0 0
Efficacy in Patients Following Platinum Based Chemotherapy by Assessment of Time to Earliest Progression by RECIST or Cancer Antigen (CA-125) or Death
Timepoint [2] 0 0
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 outcome [3] 0 0
Efficacy in Patients Following Platinum Based Chemotherapy by Assessment of Time From Randomization to Second Progression
Timepoint [3] 0 0
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 outcome [4] 0 0
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)
Timepoint [4] 0 0
Questionnaires completed by patient at baseline, Day 29 and then every 12 weeks for 12 months. Assessed until 19 Sep 2016 DCO.
Secondary outcome [5] 0 0
Efficacy of Olaparib by Time to First Subsequent Therapy or Death (TFST)
Timepoint [5] 0 0
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 outcome [6] 0 0
Efficacy of Olaparib by Time to Second Subsequent Therapy or Death (TSST)
Timepoint [6] 0 0
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 outcome [7] 0 0
Efficacy of Olaparib by Time From Randomization to Study Treatment Discontinuation or Death (TDT)
Timepoint [7] 0 0
Time elapsed from randomization to study treatment discontinuation or death. Assessed until 03 Feb 2020 DCO; up to a maximum of 75 months.
Secondary outcome [8] 0 0
Efficacy in Patients With a Deleterious or Suspected Deleterious Variant in Either of the BRCA Genes by Assessment of PFS.
Timepoint [8] 0 0
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 outcome [9] 0 0
To Determine the Exposure to Olaparib by Pharmacokinetic Analysis
Timepoint [9] 0 0
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.

Eligibility
Key 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
Minimum age
18 Years
Maximum age
130 Years
Sex
Females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
3/09/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/12/2024
Actual
Sample size
Target
Accrual to date
Final
327
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Mercy Hospital for Women - Heidelberg
Recruitment hospital [2] 0 0
The Royal Womens Hospital - Parkville
Recruitment hospital [3] 0 0
Prince of Wales Hospital - Randwick
Recruitment postcode(s) [1] 0 0
- Heidelberg
Recruitment postcode(s) [2] 0 0
- Parkville
Recruitment postcode(s) [3] 0 0
- Randwick
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Connecticut
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Maryland
Country [8] 0 0
United States of America
State/province [8] 0 0
Massachusetts
Country [9] 0 0
United States of America
State/province [9] 0 0
New Jersey
Country [10] 0 0
United States of America
State/province [10] 0 0
New York
Country [11] 0 0
United States of America
State/province [11] 0 0
Ohio
Country [12] 0 0
United States of America
State/province [12] 0 0
Tennessee
Country [13] 0 0
United States of America
State/province [13] 0 0
Wisconsin
Country [14] 0 0
Belgium
State/province [14] 0 0
Gent
Country [15] 0 0
Belgium
State/province [15] 0 0
Leuven
Country [16] 0 0
Brazil
State/province [16] 0 0
Barretos
Country [17] 0 0
Brazil
State/province [17] 0 0
Fortaleza
Country [18] 0 0
Brazil
State/province [18] 0 0
Goiânia
Country [19] 0 0
Brazil
State/province [19] 0 0
Ijuí
Country [20] 0 0
Brazil
State/province [20] 0 0
Itajai
Country [21] 0 0
Brazil
State/province [21] 0 0
Porto Alegre
Country [22] 0 0
Brazil
State/province [22] 0 0
São José do Rio Preto
Country [23] 0 0
Brazil
State/province [23] 0 0
São Paulo
Country [24] 0 0
Canada
State/province [24] 0 0
Ontario
Country [25] 0 0
Canada
State/province [25] 0 0
Quebec
Country [26] 0 0
China
State/province [26] 0 0
Beijing
Country [27] 0 0
China
State/province [27] 0 0
Changchun
Country [28] 0 0
China
State/province [28] 0 0
Changsha
Country [29] 0 0
China
State/province [29] 0 0
Chengdu
Country [30] 0 0
China
State/province [30] 0 0
Chongqing
Country [31] 0 0
China
State/province [31] 0 0
Guangzhou
Country [32] 0 0
China
State/province [32] 0 0
Hangzhou
Country [33] 0 0
China
State/province [33] 0 0
Harbin
Country [34] 0 0
China
State/province [34] 0 0
Huangzhou
Country [35] 0 0
China
State/province [35] 0 0
Ji Nan
Country [36] 0 0
China
State/province [36] 0 0
Shanghai
Country [37] 0 0
China
State/province [37] 0 0
Suzhou
Country [38] 0 0
China
State/province [38] 0 0
Xian
Country [39] 0 0
France
State/province [39] 0 0
Bordeaux
Country [40] 0 0
France
State/province [40] 0 0
Caen Cedex
Country [41] 0 0
France
State/province [41] 0 0
Lyon Cedex 08
Country [42] 0 0
France
State/province [42] 0 0
Nantes,
Country [43] 0 0
France
State/province [43] 0 0
Paris Cedex 5
Country [44] 0 0
France
State/province [44] 0 0
Paris
Country [45] 0 0
France
State/province [45] 0 0
Pierre Benite Cedex
Country [46] 0 0
France
State/province [46] 0 0
Saint Cloud
Country [47] 0 0
France
State/province [47] 0 0
Toulouse
Country [48] 0 0
France
State/province [48] 0 0
Vandoeuvre Les Nancy
Country [49] 0 0
France
State/province [49] 0 0
Villejuif Cedex
Country [50] 0 0
Germany
State/province [50] 0 0
Berlin
Country [51] 0 0
Germany
State/province [51] 0 0
Erlangen
Country [52] 0 0
Germany
State/province [52] 0 0
Essen
Country [53] 0 0
Germany
State/province [53] 0 0
Frankfurt
Country [54] 0 0
Germany
State/province [54] 0 0
Hannover
Country [55] 0 0
Germany
State/province [55] 0 0
Lübeck
Country [56] 0 0
Germany
State/province [56] 0 0
München
Country [57] 0 0
Germany
State/province [57] 0 0
Ravensburg
Country [58] 0 0
Germany
State/province [58] 0 0
Rostock
Country [59] 0 0
Israel
State/province [59] 0 0
Haifa
Country [60] 0 0
Israel
State/province [60] 0 0
Kfar Saba
Country [61] 0 0
Israel
State/province [61] 0 0
Ramat Gan
Country [62] 0 0
Italy
State/province [62] 0 0
Milano
Country [63] 0 0
Italy
State/province [63] 0 0
Modena
Country [64] 0 0
Italy
State/province [64] 0 0
Napoli
Country [65] 0 0
Italy
State/province [65] 0 0
Padova
Country [66] 0 0
Italy
State/province [66] 0 0
Roma
Country [67] 0 0
Japan
State/province [67] 0 0
Akashi-shi
Country [68] 0 0
Japan
State/province [68] 0 0
Chuo-ku
Country [69] 0 0
Japan
State/province [69] 0 0
Fukuoka
Country [70] 0 0
Japan
State/province [70] 0 0
Hidaka-shi
Country [71] 0 0
Japan
State/province [71] 0 0
Matsuyama-shi
Country [72] 0 0
Japan
State/province [72] 0 0
Niigata-shi
Country [73] 0 0
Japan
State/province [73] 0 0
Osakasayama-shi
Country [74] 0 0
Japan
State/province [74] 0 0
Sapporo-shi
Country [75] 0 0
Japan
State/province [75] 0 0
Sunto-gun
Country [76] 0 0
Korea, Republic of
State/province [76] 0 0
Seoul
Country [77] 0 0
Netherlands
State/province [77] 0 0
Amsterdam
Country [78] 0 0
Netherlands
State/province [78] 0 0
Maastricht
Country [79] 0 0
Netherlands
State/province [79] 0 0
Nijmegen
Country [80] 0 0
Netherlands
State/province [80] 0 0
Rotterdam
Country [81] 0 0
Poland
State/province [81] 0 0
Grzepnica
Country [82] 0 0
Poland
State/province [82] 0 0
Olsztyn
Country [83] 0 0
Poland
State/province [83] 0 0
Warszawa
Country [84] 0 0
Russian Federation
State/province [84] 0 0
Moscow
Country [85] 0 0
Russian Federation
State/province [85] 0 0
Saint Petersburg
Country [86] 0 0
Russian Federation
State/province [86] 0 0
St.Petersburg
Country [87] 0 0
Spain
State/province [87] 0 0
Barcelona
Country [88] 0 0
Spain
State/province [88] 0 0
Córdoba
Country [89] 0 0
Spain
State/province [89] 0 0
Gerona
Country [90] 0 0
Spain
State/province [90] 0 0
Madrid
Country [91] 0 0
Spain
State/province [91] 0 0
Pamplona
Country [92] 0 0
Spain
State/province [92] 0 0
Valencia
Country [93] 0 0
United Kingdom
State/province [93] 0 0
Birmingham
Country [94] 0 0
United Kingdom
State/province [94] 0 0
Cambridge
Country [95] 0 0
United Kingdom
State/province [95] 0 0
Coventry
Country [96] 0 0
United Kingdom
State/province [96] 0 0
Edinburgh
Country [97] 0 0
United Kingdom
State/province [97] 0 0
London
Country [98] 0 0
United Kingdom
State/province [98] 0 0
Manchester
Country [99] 0 0
United Kingdom
State/province [99] 0 0
Sutton

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
AstraZeneca
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
European Network of Gynaecological Oncological Trial Groups (ENGOT)
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/industry
Name [2] 0 0
Myriad Genetic Laboratories, Inc.
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Commercial sector/industry
Name [3] 0 0
Merck Sharp & Dohme LLC
Address [3] 0 0
Country [3] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT01874353
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Professor E Pujade-Lauraine, MD, PhD
Address 0 0
Universite de Paris Descartes, France
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01874353