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

Neoplasms, Breast Clinical Trial

— ZEST  

Official 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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04915755
• Other study ID #: 213831
• Secondary ID: 2020-003973-23
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: June 28, 2021
• Est. completion date: August 28, 2029

Study information

• Verified date: August 2023
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will assess the efficacy and safety of Niraparib in participants with either tumor mutation in the BRCA gene (tBRCAmut) HER2- breast cancer (Independent of hormone receptor [HR] status, including HR positive [+] and TNBC) or tumor BRCA wild type (tBRCAwt) TNBC with molecular disease based on the presence of circulating tumor Deoxyribonucleic acid (ctDNA) following surgery or completion of adjuvant therapy.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 40
• Est. completion date: August 28, 2029
• Est. primary completion date: March 12, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

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).

Related Conditions & MeSH terms

• Breast Neoplasms
• Neoplasms, Breast
• Triple Negative Breast Neoplasms

Intervention

Drug:
• Niraparib
Niraparib will be administered.
• Placebo
Matching placebo will be administered

Locations

Country	Name	City	State
Argentina	GSK Investigational Site	Capital Federal	Buenos Aires
Argentina	GSK Investigational Site	Capital Federal, Buenos Aires
Argentina	GSK Investigational Site	Cipoletti, Rio Negro	Río Negro
Argentina	GSK Investigational Site	Ciudad Autonoma Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autonoma Buenos Aires	Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autonoma de Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autonoma de Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autónoma de Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autónoma de Buenos Aires	Buenos Aires
Argentina	GSK Investigational Site	Cordoba	Córdova
Argentina	GSK Investigational Site	Gualeguaychu	Entre Ríos
Australia	GSK Investigational Site	Camperdown	New South Wales
Australia	GSK Investigational Site	Macquarie University	New South Wales
Australia	GSK Investigational Site	North Sydney	New South Wales
Austria	GSK Investigational Site	Innsbruck
Austria	GSK Investigational Site	Rankweil
Austria	GSK Investigational Site	Steyr
Austria	GSK Investigational Site	Wien
Belgium	GSK Investigational Site	Brussels
Belgium	GSK Investigational Site	Bruxelles
Belgium	GSK Investigational Site	Charleroi
Belgium	GSK Investigational Site	Gent
Belgium	GSK Investigational Site	Leuven
Brazil	GSK Investigational Site	Belo Horizonte	Minas Gerais
Brazil	GSK Investigational Site	Caxias do Sul	Rio Grande Do Sul
Brazil	GSK Investigational Site	Florianopolis	Santa Catarina
Brazil	GSK Investigational Site	Ondina	Bahia
Brazil	GSK Investigational Site	Porto Alegre	Rio Grande Do Sul
Brazil	GSK Investigational Site	Porto Alegre	Rio Grande Do Sul
Brazil	GSK Investigational Site	Rio de Janeiro
Brazil	GSK Investigational Site	São Paulo
Brazil	GSK Investigational Site	São Paulo
Brazil	GSK Investigational Site	Vitória	Espírito Santo
Canada	GSK Investigational Site	Calgary	Alberta
Canada	GSK Investigational Site	Halifax	Nova Scotia
Canada	GSK Investigational Site	Montreal	Quebec
Canada	GSK Investigational Site	Montreal	Quebec
Canada	GSK Investigational Site	Québec
Canada	GSK Investigational Site	Toronto	Ontario
Canada	GSK Investigational Site	Toronto	Ontario
Canada	GSK Investigational Site	Vancouver	British Columbia
Chile	GSK Investigational Site	Providencia	Región Metro De Santiago
Chile	GSK Investigational Site	Santiago	Región Metro De Santiago
Chile	GSK Investigational Site	Temuco	Región De La Araucania
Colombia	GSK Investigational Site	Barranquilla
Colombia	GSK Investigational Site	Bogotá
Colombia	GSK Investigational Site	Medellin
Colombia	GSK Investigational Site	Monteria
Colombia	GSK Investigational Site	Pereira
Finland	GSK Investigational Site	Helsinki
Finland	GSK Investigational Site	Helsinki
Finland	GSK Investigational Site	Tampere
Finland	GSK Investigational Site	Turku
France	GSK Investigational Site	Avignon Cedex 9
France	GSK Investigational Site	Bordeaux Cedex
France	GSK Investigational Site	Caen
France	GSK Investigational Site	Clermont-Ferrand cedex
France	GSK Investigational Site	Dijon
France	GSK Investigational Site	Marseille Cedex 20
France	GSK Investigational Site	Montpellier
France	GSK Investigational Site	Pierre-Bénite cedex
France	GSK Investigational Site	Rouen
France	GSK Investigational Site	Saint-Cloud
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Erlangen	Bayern
Germany	GSK Investigational Site	Essen	Nordrhein-Westfalen
Germany	GSK Investigational Site	Hannover	Niedersachsen
Germany	GSK Investigational Site	Koeln	Nordrhein-Westfalen
Germany	GSK Investigational Site	Mannheim	Baden-Wuerttemberg
Germany	GSK Investigational Site	Muenchen	Bayern
Germany	GSK Investigational Site	Offenbach	Hessen
Germany	GSK Investigational Site	Ulm	Baden-Wuerttemberg
Hungary	GSK Investigational Site	Budapest
Hungary	GSK Investigational Site	Debrecen
Hungary	GSK Investigational Site	Gyor
Hungary	GSK Investigational Site	Gyula
Hungary	GSK Investigational Site	Zalaegerszeg
Ireland	GSK Investigational Site	Dublin
Ireland	GSK Investigational Site	Dublin
Israel	GSK Investigational Site	Beer Sheva
Israel	GSK Investigational Site	Haifa
Israel	GSK Investigational Site	Jerusalem
Israel	GSK Investigational Site	Jerusalem
Israel	GSK Investigational Site	Petach Tikva
Israel	GSK Investigational Site	Rehovot
Israel	GSK Investigational Site	Tel Aviv
Italy	GSK Investigational Site	Aviano (PN)	Friuli-Venezia-Giulia
Italy	GSK Investigational Site	Bologna	Emilia-Romagna
Italy	GSK Investigational Site	Brindisi	Puglia
Italy	GSK Investigational Site	Candiolo	Piemonte
Italy	GSK Investigational Site	Catania	Sicilia
Italy	GSK Investigational Site	Cremona	Lombardia
Italy	GSK Investigational Site	Genova	Liguria
Italy	GSK Investigational Site	Macerata	Marche
Italy	GSK Investigational Site	Meldola (FC)	Emilia-Romagna
Italy	GSK Investigational Site	Milano	Lombardia
Italy	GSK Investigational Site	Milano	Lombardia
Italy	GSK Investigational Site	Monza (MB)	Lombardia
Italy	GSK Investigational Site	Napoli	Campania
Italy	GSK Investigational Site	Negrar (Verona)	Veneto
Italy	GSK Investigational Site	Padova	Veneto
Italy	GSK Investigational Site	Torrette Di Ancona	Marche
Japan	GSK Investigational Site	Aichi
Japan	GSK Investigational Site	Chiba
Japan	GSK Investigational Site	Ehime
Japan	GSK Investigational Site	Fukuoka
Japan	GSK Investigational Site	Hiroshima
Japan	GSK Investigational Site	Hokkaido
Japan	GSK Investigational Site	Kagoshima
Japan	GSK Investigational Site	Kanagawa
Japan	GSK Investigational Site	Kanagawa
Japan	GSK Investigational Site	Kanagawa
Japan	GSK Investigational Site	Okayama
Japan	GSK Investigational Site	Osaka
Japan	GSK Investigational Site	Osaka
Japan	GSK Investigational Site	Saitama
Japan	GSK Investigational Site	Saitama
Japan	GSK Investigational Site	Saitama
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Tokyo
Mexico	GSK Investigational Site	Ciudad de Mexico
Mexico	GSK Investigational Site	León, Guanajuato	Guanajuato
Mexico	GSK Investigational Site	Mexico City
Mexico	GSK Investigational Site	Monterrey	Nuevo León
Mexico	GSK Investigational Site	Monterrey	Nuevo León
Netherlands	GSK Investigational Site	Alkmaar
Netherlands	GSK Investigational Site	Den Haag
Netherlands	GSK Investigational Site	Leeuwarden
Netherlands	GSK Investigational Site	Maastricht
Netherlands	GSK Investigational Site	Rotterdam
Netherlands	GSK Investigational Site	Zwolle
Norway	GSK Investigational Site	Drammen
Norway	GSK Investigational Site	Stavanger
Poland	GSK Investigational Site	Katowice
Poland	GSK Investigational Site	Krakow
Poland	GSK Investigational Site	Krakow
Poland	GSK Investigational Site	Olsztyn
Poland	GSK Investigational Site	Poznan
Poland	GSK Investigational Site	Rzeszow
Poland	GSK Investigational Site	Siedlce
Poland	GSK Investigational Site	Szczecin
Poland	GSK Investigational Site	Warszawa
Poland	GSK Investigational Site	Wroclaw
Portugal	GSK Investigational Site	Lisboa
Portugal	GSK Investigational Site	Loures
Portugal	GSK Investigational Site	Vila Nova de Gaia
Romania	GSK Investigational Site	Bucharest
Romania	GSK Investigational Site	Bucharest
Romania	GSK Investigational Site	Bucharest
Romania	GSK Investigational Site	Bucuresti
Romania	GSK Investigational Site	Cluj-Napoca
Romania	GSK Investigational Site	Craiova
Romania	GSK Investigational Site	Craiova
Romania	GSK Investigational Site	Iasi
Romania	GSK Investigational Site	Otopeni
Romania	GSK Investigational Site	Timisoara
Russian Federation	GSK Investigational Site	Arkhangelsk
Russian Federation	GSK Investigational Site	Chelyabinsk
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Omsk
Russian Federation	GSK Investigational Site	Pushkin
Russian Federation	GSK Investigational Site	Saint Petersburg
Russian Federation	GSK Investigational Site	Saint-Petersburg
Russian Federation	GSK Investigational Site	St. Petersburg
Russian Federation	GSK Investigational Site	St.Peterburg
South Africa	GSK Investigational Site	Cape Town
South Africa	GSK Investigational Site	Kraaifontein	Western Province
South Africa	GSK Investigational Site	Port Elizabeth
South Africa	GSK Investigational Site	Pretoria
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Cáceres
Spain	GSK Investigational Site	Córdoba
Spain	GSK Investigational Site	Granada
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Málaga
Spain	GSK Investigational Site	Murcia
Spain	GSK Investigational Site	Santiago de Compostela
Spain	GSK Investigational Site	Valencia
Spain	GSK Investigational Site	Zaragoza
Switzerland	GSK Investigational Site	Basel
Switzerland	GSK Investigational Site	Zuerich
United Kingdom	GSK Investigational Site	Bath
United Kingdom	GSK Investigational Site	Brighton
United Kingdom	GSK Investigational Site	Cardiff
United Kingdom	GSK Investigational Site	Coventry	Warwickshire
United Kingdom	GSK Investigational Site	Edinburgh
United Kingdom	GSK Investigational Site	Leeds
United Kingdom	GSK Investigational Site	London
United Kingdom	GSK Investigational Site	London
United Kingdom	GSK Investigational Site	Maidstone
United Kingdom	GSK Investigational Site	Manchester
United Kingdom	GSK Investigational Site	Sutton	Surrey
United Kingdom	GSK Investigational Site	Wigan.
United States	GSK Investigational Site	Albuquerque	New Mexico
United States	GSK Investigational Site	Ann Arbor	Michigan
United States	GSK Investigational Site	Aurora	Colorado
United States	GSK Investigational Site	Austin	Texas
United States	GSK Investigational Site	Burbank	California
United States	GSK Investigational Site	Chicago	Illinois
United States	GSK Investigational Site	Dallas	Texas
United States	GSK Investigational Site	Dallas	Texas
United States	GSK Investigational Site	Duarte	California
United States	GSK Investigational Site	Everett	Washington
United States	GSK Investigational Site	Fargo	North Dakota
United States	GSK Investigational Site	Fort Worth	Texas
United States	GSK Investigational Site	Houston	Texas
United States	GSK Investigational Site	New Haven	Connecticut
United States	GSK Investigational Site	New York	New York
United States	GSK Investigational Site	Norfolk	Virginia
United States	GSK Investigational Site	Orange	California
United States	GSK Investigational Site	Palo Alto	California
United States	GSK Investigational Site	Philadelphia	Pennsylvania
United States	GSK Investigational Site	Pittsburgh	Pennsylvania
United States	GSK Investigational Site	San Antonio	Texas
United States	GSK Investigational Site	San Francisco	California
United States	GSK Investigational Site	Sioux Falls	South Dakota
United States	GSK Investigational Site	Skokie	Illinois
United States	GSK Investigational Site	Tyler	Texas

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Canada,  Chile,  Colombia,  Finland,  France,  Germany,  Hungary,  Ireland,  Israel,  Italy,  Japan,  Mexico,  Netherlands,  Norway,  Poland,  Portugal,  Romania,  Russian Federation,  South Africa,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with treatment emergent adverse event (TEAEs), serious adverse events (SAEs), and adverse events of special interest (AESIs)	Number of participants with TEAEs, SAEs, and AESIs will be assessed.	Up to approximately 34 months
Primary	Number of participants with clinically significant changes in Eastern Co-operative Oncology Group (ECOG) performance status	The performance status will be assessed using ECOG scale, where Grade 0 (fully active), Grade 1 (restricted in physically strenuous activity), Grade 2 (ambulatory and capable of all self-care), Grade 3 (capable of only limited self-care) and Grade 4 (completely disabled). Change in ECOG performance from baseline will be assessed.	Up to approximately 34 months
Primary	Number of participants with clinically significant changes in relevant laboratory parameters	Number of participants with clinically significant changes in hematology and clinical chemistry parameters will be assessed.	Up to approximately 34 months
Primary	Number of participants with clinically significant changes in vital signs	Number of participants with clinically significant changes in vital signs will be assessed.	Up to approximately 34 months
Primary	Number of participants with use of concomitant medications	Number of participants using concomitant medications will be assessed.	Up to approximately 34 months