Clinical trial NCT04915755: 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
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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Neoplasms, Breast
Keywords: Niraparib
Breast cancer susceptibility gene
Human epidermal growth factor-2 negative (HER2)
Breast cancer
Triple negative breast cancer (TNBC)
Circulating tumor Deoxyribonucleic acid (ctDNA)
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2021-06-07
Enrollment: 43
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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).

Primary outcomes:
measure: Number of participants with treatment emergent adverse event (TEAEs), serious adverse events (SAEs), and adverse events of special interest (AESIs)
timeFrame: Up to approximately 34 months
measure: Number of participants with clinically significant changes in Eastern Co-operative Oncology Group (ECOG) performance status
timeFrame: Up to approximately 34 months
measure: Number of participants with clinically significant changes in relevant laboratory parameters
timeFrame: Up to approximately 34 months
measure: Number of participants with clinically significant changes in vital signs
timeFrame: Up to approximately 34 months
measure: Number of participants with use of concomitant medications
timeFrame: Up to approximately 34 months
Secondary outcomes:
Other outcomes:
Locations:
city: Burbank
country: United States
facility: GSK Investigational Site
state: California
city: Duarte
country: United States
facility: GSK Investigational Site
state: California
city: Orange
country: United States
facility: GSK Investigational Site
state: California
city: Palo Alto
country: United States
facility: GSK Investigational Site
state: California
city: San Francisco
country: United States
facility: GSK Investigational Site
state: California
city: Aurora
country: United States
facility: GSK Investigational Site
state: Colorado
city: Chicago
country: United States
facility: GSK Investigational Site
state: Illinois
city: Skokie
country: United States
facility: GSK Investigational Site
state: Illinois
city: Ann Arbor
country: United States
facility: GSK Investigational Site
state: Michigan
city: Albuquerque
country: United States
facility: GSK Investigational Site
state: New Mexico
city: New York
country: United States
facility: GSK Investigational Site
state: New York
city: Fargo
country: United States
facility: GSK Investigational Site
state: North Dakota
city: Philadelphia
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Pittsburgh
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Sioux Falls
country: United States
facility: GSK Investigational Site
state: South Dakota
city: Austin
country: United States
facility: GSK Investigational Site
state: Texas
city: Dallas
country: United States
facility: GSK Investigational Site
state: Texas
city: Dallas
country: United States
facility: GSK Investigational Site
state: Texas
city: Fort Worth
country: United States
facility: GSK Investigational Site
state: Texas
city: Houston
country: United States
facility: GSK Investigational Site
state: Texas
city: San Antonio
country: United States
facility: GSK Investigational Site
state: Texas
city: Tyler
country: United States
facility: GSK Investigational Site
state: Texas
city: Norfolk
country: United States
facility: GSK Investigational Site
state: Virginia
city: Everett
country: United States
facility: GSK Investigational Site
state: Washington
city: Capital Federal
country: Argentina
facility: GSK Investigational Site
state: Buenos Aires
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: GSK Investigational Site
state: Buenos Aires
city: Ciudad Autónoma de Buenos Aires
country: Argentina
facility: GSK Investigational Site
state: Buenos Aires
city: Gualeguaychu
country: Argentina
facility: GSK Investigational Site
state: Entre Ríos
city: Cipoletti, Rio Negro
country: Argentina
facility: GSK Investigational Site
state: Río Negro
city: Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Capital Federal, Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Ciudad Autónoma de Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Camperdown
country: Australia
facility: GSK Investigational Site
state: New South Wales
city: Macquarie University
country: Australia
facility: GSK Investigational Site
state: New South Wales
city: North Sydney
country: Australia
facility: GSK Investigational Site
state: New South Wales
city: Innsbruck
country: Austria
facility: GSK Investigational Site
city: Rankweil
country: Austria
facility: GSK Investigational Site
city: Steyr
country: Austria
facility: GSK Investigational Site
city: Wien
country: Austria
facility: GSK Investigational Site
city: Brussels
country: Belgium
facility: GSK Investigational Site
city: Bruxelles
country: Belgium
facility: GSK Investigational Site
city: Charleroi
country: Belgium
facility: GSK Investigational Site
city: Gent
country: Belgium
facility: GSK Investigational Site
city: Leuven
country: Belgium
facility: GSK Investigational Site
city: Ondina
country: Brazil
facility: GSK Investigational Site
state: Bahia
city: Vitória
country: Brazil
facility: GSK Investigational Site
state: Espírito Santo
city: Belo Horizonte
country: Brazil
facility: GSK Investigational Site
state: Minas Gerais
city: Caxias do Sul
country: Brazil
facility: GSK Investigational Site
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: GSK Investigational Site
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: GSK Investigational Site
state: Rio Grande Do Sul
city: Florianopolis
country: Brazil
facility: GSK Investigational Site
state: Santa Catarina
city: Rio de Janeiro
country: Brazil
facility: GSK Investigational Site
city: São Paulo
country: Brazil
facility: GSK Investigational Site
city: São Paulo
country: Brazil
facility: GSK Investigational Site
city: Calgary
country: Canada
facility: GSK Investigational Site
state: Alberta
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Montreal
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Québec
country: Canada
facility: GSK Investigational Site
city: Temuco
country: Chile
facility: GSK Investigational Site
state: Región De La Araucania
city: Providencia
country: Chile
facility: GSK Investigational Site
state: Región Metro De Santiago
city: Santiago
country: Chile
facility: GSK Investigational Site
state: Región Metro De Santiago
city: Helsinki
country: Finland
facility: GSK Investigational Site
city: Helsinki
country: Finland
facility: GSK Investigational Site
city: Turku
country: Finland
facility: GSK Investigational Site
city: Avignon Cedex 9
country: France
facility: GSK Investigational Site
city: Bordeaux Cedex
country: France
facility: GSK Investigational Site
city: Caen
country: France
facility: GSK Investigational Site
city: Clermont-Ferrand cedex
country: France
facility: GSK Investigational Site
city: Dijon
country: France
facility: GSK Investigational Site
city: Marseille Cedex 20
country: France
facility: GSK Investigational Site
city: Montpellier
country: France
facility: GSK Investigational Site
city: Pierre-Bénite cedex
country: France
facility: GSK Investigational Site
city: Rouen
country: France
facility: GSK Investigational Site
city: Saint-Cloud
country: France
facility: GSK Investigational Site
city: Mannheim
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Ulm
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Erlangen
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Muenchen
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Essen
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Koeln
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Debrecen
country: Hungary
facility: GSK Investigational Site
city: Dublin
country: Ireland
facility: GSK Investigational Site
city: Dublin
country: Ireland
facility: GSK Investigational Site
city: Beer Sheva
country: Israel
facility: GSK Investigational Site
city: Haifa
country: Israel
facility: GSK Investigational Site
city: Jerusalem
country: Israel
facility: GSK Investigational Site
city: Jerusalem
country: Israel
facility: GSK Investigational Site
city: Petach Tikva
country: Israel
facility: GSK Investigational Site
city: Rehovot
country: Israel
facility: GSK Investigational Site
city: Tel Aviv
country: Israel
facility: GSK Investigational Site
city: Napoli
country: Italy
facility: GSK Investigational Site
state: Campania
city: Bologna
country: Italy
facility: GSK Investigational Site
state: Emilia-Romagna
city: Meldola (FC)
country: Italy
facility: GSK Investigational Site
state: Emilia-Romagna
city: Genova
country: Italy
facility: GSK Investigational Site
state: Liguria
city: Milano
country: Italy
facility: GSK Investigational Site
state: Lombardia
city: Milano
country: Italy
facility: GSK Investigational Site
state: Lombardia
city: Monza (MB)
country: Italy
facility: GSK Investigational Site
state: Lombardia
city: Macerata
country: Italy
facility: GSK Investigational Site
state: Marche
city: Torrette Di Ancona
country: Italy
facility: GSK Investigational Site
state: Marche
city: Candiolo
country: Italy
facility: GSK Investigational Site
state: Piemonte
city: Brindisi
country: Italy
facility: GSK Investigational Site
state: Puglia
city: Catania
country: Italy
facility: GSK Investigational Site
state: Sicilia
city: Negrar (Verona)
country: Italy
facility: GSK Investigational Site
state: Veneto
city: Padova
country: Italy
facility: GSK Investigational Site
state: Veneto
city: Aichi
country: Japan
facility: GSK Investigational Site
city: Chiba
country: Japan
facility: GSK Investigational Site
city: Ehime
country: Japan
facility: GSK Investigational Site
city: Fukuoka
country: Japan
facility: GSK Investigational Site
city: Hiroshima
country: Japan
facility: GSK Investigational Site
city: Hokkaido
country: Japan
facility: GSK Investigational Site
city: Kagoshima
country: Japan
facility: GSK Investigational Site
city: Kanagawa
country: Japan
facility: GSK Investigational Site
city: Kanagawa
country: Japan
facility: GSK Investigational Site
city: Kanagawa
country: Japan
facility: GSK Investigational Site
city: Okayama
country: Japan
facility: GSK Investigational Site
city: Osaka
country: Japan
facility: GSK Investigational Site
city: Osaka
country: Japan
facility: GSK Investigational Site
city: Saitama
country: Japan
facility: GSK Investigational Site
city: Saitama
country: Japan
facility: GSK Investigational Site
city: Saitama
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Guanajuato
country: Mexico
facility: GSK Investigational Site
state: Leon
city: Monterrey
country: Mexico
facility: GSK Investigational Site
state: Nuevo León
city: Monterrey
country: Mexico
facility: GSK Investigational Site
state: Nuevo León
city: Ciudad de Mexico
country: Mexico
facility: GSK Investigational Site
city: Alkmaar
country: Netherlands
facility: GSK Investigational Site
city: Den Haag
country: Netherlands
facility: GSK Investigational Site
city: Leeuwarden
country: Netherlands
facility: GSK Investigational Site
city: Maastricht
country: Netherlands
facility: GSK Investigational Site
city: Rotterdam
country: Netherlands
facility: GSK Investigational Site
city: Zwolle
country: Netherlands
facility: GSK Investigational Site
city: Drammen
country: Norway
facility: GSK Investigational Site
city: Stavanger
country: Norway
facility: GSK Investigational Site
city: Katowice
country: Poland
facility: GSK Investigational Site
city: Krakow
country: Poland
facility: GSK Investigational Site
city: Krakow
country: Poland
facility: GSK Investigational Site
city: Olsztyn
country: Poland
facility: GSK Investigational Site
city: Poznan
country: Poland
facility: GSK Investigational Site
city: Rzeszow
country: Poland
facility: GSK Investigational Site
city: Siedlce
country: Poland
facility: GSK Investigational Site
city: Szczecin
country: Poland
facility: GSK Investigational Site
city: Warszawa
country: Poland
facility: GSK Investigational Site
city: Wroclaw
country: Poland
facility: GSK Investigational Site
city: Lisboa
country: Portugal
facility: GSK Investigational Site
city: Loures
country: Portugal
facility: GSK Investigational Site
city: Bucharest
country: Romania
facility: GSK Investigational Site
city: Bucharest
country: Romania
facility: GSK Investigational Site
city: Bucharest
country: Romania
facility: GSK Investigational Site
city: Bucuresti
country: Romania
facility: GSK Investigational Site
city: Cluj-Napoca
country: Romania
facility: GSK Investigational Site
city: Craiova
country: Romania
facility: GSK Investigational Site
city: Otopeni
country: Romania
facility: GSK Investigational Site
city: Timisoara
country: Romania
facility: GSK Investigational Site
city: Chelyabinsk
country: Russian Federation
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Omsk
country: Russian Federation
facility: GSK Investigational Site
city: Pushkin
country: Russian Federation
facility: GSK Investigational Site
city: Saint Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: St. Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: St.Peterburg
country: Russian Federation
facility: GSK Investigational Site
city: Cape Town
country: South Africa
facility: GSK Investigational Site
city: Port Elizabeth
country: South Africa
facility: GSK Investigational Site
city: Pretoria
country: South Africa
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Cáceres
country: Spain
facility: GSK Investigational Site
city: Córdoba
country: Spain
facility: GSK Investigational Site
city: Granada
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Murcia
country: Spain
facility: GSK Investigational Site
city: Málaga
country: Spain
facility: GSK Investigational Site
city: Santiago de Compostela
country: Spain
facility: GSK Investigational Site
city: Valencia
country: Spain
facility: GSK Investigational Site
city: Zaragoza
country: Spain
facility: GSK Investigational Site
city: Basel
country: Switzerland
facility: GSK Investigational Site
city: Sutton
country: United Kingdom
facility: GSK Investigational Site
state: Surrey
city: Coventry
country: United Kingdom
facility: GSK Investigational Site
state: Warwickshire
city: Bath
country: United Kingdom
facility: GSK Investigational Site
city: Brighton
country: United Kingdom
facility: GSK Investigational Site
city: Cardiff
country: United Kingdom
facility: GSK Investigational Site
city: Edinburgh
country: United Kingdom
facility: GSK Investigational Site
city: Leeds
country: United Kingdom
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
city: Maidstone
country: United Kingdom
facility: GSK Investigational Site
city: Manchester
country: United Kingdom
facility: GSK Investigational Site
city: Wigan.
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: