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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
9/10/2024

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
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United States of America
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Alabama
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California
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Colorado
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Connecticut
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Illinois
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Maryland
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Massachusetts
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New Jersey
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New York
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Ohio
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Tennessee
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Wisconsin
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Belgium
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Gent
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Belgium
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Leuven
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Brazil
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Barretos
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Brazil
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Fortaleza
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Goiânia
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Ijuí
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Itajai
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Porto Alegre
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São José do Rio Preto
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Ontario
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China
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China
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Chongqing
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China
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Guangzhou
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China
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Hangzhou
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China
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Harbin
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China
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Huangzhou
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China
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Ji Nan
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China
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Shanghai
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China
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Suzhou
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China
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Xian
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France
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Bordeaux
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France
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Caen Cedex
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France
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Lyon Cedex 08
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France
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Nantes,
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France
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Paris Cedex 5
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France
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Paris
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France
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Pierre Benite Cedex
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France
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Saint Cloud
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France
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Toulouse
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France
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Vandoeuvre Les Nancy
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France
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Villejuif Cedex
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Germany
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Berlin
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Germany
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Erlangen
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Germany
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Essen
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Frankfurt
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Hannover
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Lübeck
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Germany
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München
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Germany
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Ravensburg
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Rostock
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Israel
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Haifa
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Israel
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Kfar Saba
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Israel
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Ramat Gan
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Italy
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Milano
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Italy
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Modena
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Napoli
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Italy
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Padova
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Roma
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Chuo-ku
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Fukuoka
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Japan
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Hidaka-shi
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Matsuyama-shi
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Niigata-shi
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Sapporo-shi
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Japan
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Sunto-gun
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Korea, Republic of
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Seoul
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Netherlands
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Amsterdam
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Maastricht
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Nijmegen
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Rotterdam
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Poland
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Grzepnica
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Poland
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Olsztyn
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Poland
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Warszawa
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Russian Federation
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Moscow
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Russian Federation
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Saint Petersburg
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Russian Federation
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St.Petersburg
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Spain
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Barcelona
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Spain
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Córdoba
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Spain
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Gerona
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Spain
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Madrid
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Spain
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Pamplona
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Spain
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Valencia
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United Kingdom
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Birmingham
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United Kingdom
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Cambridge
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United Kingdom
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Coventry
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United Kingdom
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Edinburgh
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United Kingdom
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London
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United Kingdom
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Manchester
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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
Frenel JS, Kim JW, Aryal N, Asher R, Berton D, Vidal L, Pautier P, Ledermann JA, Penson RT, Oza AM, Korach J, Huzarski T, Pignata S, Colombo N, Park-Simon TW, Tamura K, Sonke GS, Freimund AE, Lee CK, Pujade-Lauraine E. Efficacy of subsequent chemotherapy for patients with BRCA1/2-mutated recurrent epithelial ovarian cancer progressing on olaparib versus placebo maintenance: post-hoc analyses of the SOLO2/ENGOT Ov-21 trial. Ann Oncol. 2022 Oct;33(10):1021-1028. doi: 10.1016/j.annonc.2022.06.011. Epub 2022 Jun 27.
Tattersall A, Ryan N, Wiggans AJ, Rogozinska E, Morrison J. Poly(ADP-ribose) polymerase (PARP) inhibitors for the treatment of ovarian cancer. Cochrane Database Syst Rev. 2022 Feb 16;2(2):CD007929. doi: 10.1002/14651858.CD007929.pub4.
Poveda A, Floquet A, Ledermann JA, Asher R, Penson RT, Oza AM, Korach J, Huzarski T, Pignata S, Friedlander M, Baldoni A, Park-Simon TW, Tamura K, Sonke GS, Lisyanskaya A, Kim JH, Filho EA, Milenkova T, Lowe ES, Rowe P, Vergote I, Pujade-Lauraine E; SOLO2/ENGOT-Ov21 investigators. Olaparib tablets as maintenance therapy in patients with platinum-sensitive relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a final analysis of a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2021 May;22(5):620-631. doi: 10.1016/S1470-2045(21)00073-5. Epub 2021 Mar 18. Erratum In: Lancet Oncol. 2024 Jul;25(7):e284. doi: 10.1016/S1470-2045(24)00317-6.
Tjokrowidjaja A, Lee CK, Friedlander M, Gebski V, Gladieff L, Ledermann J, Penson R, Oza A, Korach J, Huzarski T, Manso L, Pisano C, Asher R, Lord SJ, Kim SI, Lee JY, Colombo N, Park-Simon TW, Fujiwara K, Sonke G, Vergote I, Kim JW, Pujade-Lauraine E. Concordance between CA-125 and RECIST progression in patients with germline BRCA-mutated platinum-sensitive relapsed ovarian cancer treated in the SOLO2 trial with olaparib as maintenance therapy after response to chemotherapy. Eur J Cancer. 2020 Nov;139:59-67. doi: 10.1016/j.ejca.2020.08.021. Epub 2020 Sep 23.
Friedlander M, Gebski V, Gibbs E, Davies L, Bloomfield R, Hilpert F, Wenzel LB, Eek D, Rodrigues M, Clamp A, Penson RT, Provencher D, Korach J, Huzarski T, Vidal L, Salutari V, Scott C, Nicoletto MO, Tamura K, Espinoza D, Joly F, Pujade-Lauraine E. Health-related quality of life and patient-centred outcomes with olaparib maintenance after chemotherapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT Ov-21): a placebo-controlled, phase 3 randomised trial. Lancet Oncol. 2018 Aug;19(8):1126-1134. doi: 10.1016/S1470-2045(18)30343-7. Epub 2018 Jul 17.
Pujade-Lauraine E, Ledermann JA, Selle F, Gebski V, Penson RT, Oza AM, Korach J, Huzarski T, Poveda A, Pignata S, Friedlander M, Colombo N, Harter P, Fujiwara K, Ray-Coquard I, Banerjee S, Liu J, Lowe ES, Bloomfield R, Pautier P; SOLO2/ENGOT-Ov21 investigators. Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2017 Sep;18(9):1274-1284. doi: 10.1016/S1470-2045(17)30469-2. Epub 2017 Jul 25. Erratum In: Lancet Oncol. 2017 Sep;18(9):e510. doi: 10.1016/S1470-2045(17)30639-3.
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