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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04915755




Registration number
NCT04915755
Ethics application status
Date submitted
1/06/2021
Date registered
7/06/2021

Titles & IDs
Public title
Efficacy and Safety Comparison of Niraparib to Placebo in Participants With Human Epidermal Growth Factor 2 Negative (HER2-) Breast Cancer Susceptibility Gene Mutation (BRCAmut) or Triple-Negative Breast Cancer (TNBC) With Molecular Disease
Scientific title
A Randomized Phase 3 Double-Blinded Study Comparing the Efficacy and Safety of Niraparib to Placebo in Participants With Either HER2-Negative BRCA-Mutated or Triple-Negative Breast Cancer With Molecular Disease Based on Presence of Circulating Tumor DNA After Definitive Therapy (ZEST)
Secondary ID [1] 0 0
2020-003973-23
Secondary ID [2] 0 0
213831
Universal Trial Number (UTN)
Trial acronym
ZEST
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Neoplasms, Breast 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Niraparib
Treatment: Drugs - Placebo

Experimental: Cohort1:Participants with tBRCAmut HER2-breast cancer(Independent of HR status,including HR+andTNBC) - Eligible participants will receive either Niraparib or Placebo.

Experimental: Cohort 2: Participants with tBRCAwt TNBC - Eligible participants will receive either Niraparib or Placebo.


Treatment: Drugs: Niraparib
Niraparib will be administered.

Treatment: Drugs: Placebo
Matching placebo will be administered
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of participants with treatment emergent adverse event (TEAEs), serious adverse events (SAEs), and adverse events of special interest (AESIs)
Timepoint [1] 0 0
Up to approximately 34 months
Primary outcome [2] 0 0
Number of participants with clinically significant changes in Eastern Co-operative Oncology Group (ECOG) performance status
Timepoint [2] 0 0
Up to approximately 34 months
Primary outcome [3] 0 0
Number of participants with clinically significant changes in relevant laboratory parameters
Timepoint [3] 0 0
Up to approximately 34 months
Primary outcome [4] 0 0
Number of participants with clinically significant changes in vital signs
Timepoint [4] 0 0
Up to approximately 34 months
Primary outcome [5] 0 0
Number of participants with use of concomitant medications
Timepoint [5] 0 0
Up to approximately 34 months

Eligibility
Key inclusion criteria
* Stage I to III breast cancer with surgical resection of the primary tumor that is confirmed to be either: TNBC, irrespective of BRCA status or HR+/HER2- breast cancer with a known and documented deleterious or suspected deleterious tBRCA mutation.
* Estrogen receptor (ER) and/or progesterone receptor (PgR) negativity is defined as immunohistochemistry (IHC) nuclear staining less than (<) 1 percentage (%), or by Allred scoring system where TNBC is defined to be 0 out of 8 or 2 out of 8, or staining in <1 % of cancer cells.
* Completed prior standard therapy for curative intent.
* Participants with HR+ breast cancer must be on a stable regimen of endocrine therapy.
* Detectable ctDNA as measured by central testing.
* An archival tumor tissue specimen of the primary tumor sufficient in quality and quantity for ctDNA assay design and tBRCA and Homologous recombination deficiency (HRD) testing is required.
* An Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Prior treatment with a Poly Adenosine-diphosphate Ribose Polymerase (PARP) inhibitor.
* Current treatment with a Cyclin-dependent kinase (CDK)4/6 inhibitor or endocrine therapy other than anastrozole, letrozole, exemestane, and tamoxifen with or without ovarian suppression.
* Participants have any sign of metastasis or local recurrence after comprehensive assessment conducted per protocol.
* Participants have shown no definitive response to preoperative chemotherapy by pathologic, radiographic or clinical evaluation, in cases where preoperative chemotherapy was administered.
* Participants have inadequately treated or controlled hypertension.
* Participants have received live vaccine within 30 days of planned start of study randomization.
* Participants have a second primary malignancy.
* Exceptions are the following: (a) Adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, Ductal carcinoma in situ (DCIS) of the breast, Stage I Grade 1 endometrial carcinoma. (b) Other solid tumors and lymphomas (without bone marrow involvement) diagnosed >=5 years prior to randomization and treated with no evidence of disease recurrence and for whom no more than 1 line of chemotherapy was applied.
* Participant is pregnant, breastfeeding, or expecting to conceive children while receiving study treatment and/or for up to 180 days after the last dose of study treatment (except France).
* Participant is immunocompromised. Participants with splenectomy are allowed. Participants with known human immunodeficiency virus (HIV) are allowed if they meet protocol-defined criteria.
* Participants have a known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).

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 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
28/06/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/12/2025
Actual
Sample size
Target
Accrual to date
Final
43
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
GSK Investigational Site - Camperdown
Recruitment hospital [2] 0 0
GSK Investigational Site - Macquarie University
Recruitment hospital [3] 0 0
GSK Investigational Site - North Sydney
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2109 - Macquarie University
Recruitment postcode(s) [3] 0 0
2060 - North Sydney
Recruitment outside Australia
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United States of America
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California
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Colorado
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Illinois
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Michigan
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New York
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North Dakota
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Pennsylvania
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Texas
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Virginia
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Washington
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Buenos Aires
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Río Negro
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Capital Federal, Buenos Aires
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Rankweil
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Jerusalem
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Israel
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Petach Tikva
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Rehovot
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Tel Aviv
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Campania
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Leon
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Loures
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Romania
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Cluj-Napoca
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Russian Federation
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Russian Federation
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Moscow
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Russian Federation
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Omsk
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Pushkin
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Russian Federation
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St.Peterburg
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Cape Town
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Port Elizabeth
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South Africa
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Pretoria
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Spain
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Barcelona
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Spain
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Cáceres
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Spain
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Córdoba
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Spain
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Granada
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Spain
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Madrid
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Spain
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Murcia
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Spain
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Málaga
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Spain
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Santiago de Compostela
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Spain
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Valencia
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Spain
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Zaragoza
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Switzerland
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Basel
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United Kingdom
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Surrey
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United Kingdom
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Warwickshire
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United Kingdom
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Bath
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United Kingdom
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Brighton
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Cardiff
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Edinburgh
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United Kingdom
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Leeds
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United Kingdom
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London
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United Kingdom
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Maidstone
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United Kingdom
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Manchester
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United Kingdom
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Wigan.

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Qualified researchers may request access to anonymized individual patient-level data (IPD) and related study documents of the eligible studies via the Data Sharing Portal. Details on GSK's data sharing criteria can be found at: https://www.gsk.com/en-gb/innovation/trials/data-transparency/

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR)
When will data be available (start and end dates)?
Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.
Available to whom?
Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension may be granted, when justified, for up to 6 months.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://www.gsk.com/en-gb/innovation/trials/data-transparency/


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04915755