Study of Nivolumab Versus Placebo in Combination With Neoadjuvant Chemotherapy and Adjuvant Endocrine Therapy in Participants With High-risk, Estrogen Receptor-Positive (ER+), Human Epidermal Growth Factor Receptor 2-Negative (HER2-) Primary Breast Cancer
Clinicaltrials.gov identifier recruitment status First Posted Last update posted
NCT04109066 Recruiting September 30, 2019 December 2, 2021

study description
Brief Summary

A randomized multi-arm study evaluating the efficacy and safety of nivolumab versus placebo in combination with neoadjuvant (pre-surgery)chemotherapy and adjuvant (post-surgery) endocrine therapy in participants with high-risk, estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+, HER2-) early stage breast cancer.

Condition or Disease: Breast Cancer
Intervention/treatment: Biological: nivolumab
Drug: paclitaxel (PTX)
Other: nivolumab placebo
Drug: anthracycline
Drug: cyclophosphamide
Drug: Endocrine Therapy
Procedure: Surgery
Phase: Phase 3
Detailed Description

N/A


study design
Study Type: Interventional
Estimated Enrollment : 1200 participants
Intervention Model : Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Multicenter, Double-blind, Placebo-controlled Phase 3 Study of Nivolumab Versus Placebo in Combination With Neoadjuvant Chemotherapy and Adjuvant Endocrine Therapy in Patients With High-risk, Estrogen Receptor-Positive (ER+), Human Epidermal Growth Factor Receptor 2-Negative (HER2-) Primary Breast Cancer
Actual Study Start Date: November 2019
Estimated Primary Completion Date: June 2032
Estimated Study Completion Date: June 2032

Arms and interventions
Arm Intervention/treatment
Experimental: Arm A: Nivolumab combined with neoadjuvant CT and adjuvant ET
Nivolumab with paclitaxel followed by nivolumab with anthracycline + cyclophosphamide as neoadjuvant (pre-surgery) treatment, then nivolumab with adjuvant (post-surgery) endocrine therapy of investigator's choice
Biological: nivolumab
Specified Dose on Specified days

Drug: paclitaxel (PTX)
Specified dose on Specified days

Drug: anthracycline
Specified dose on Specified days

Drug: cyclophosphamide
Specified dose on Specified days

Drug: Endocrine Therapy
Variable endocrine therapy of investigators choice

Procedure: Surgery
Surgery for breast cancer
Placebo Comparator: Arm B: Placebo combined with neoadjuvant CT and adjuvant ET
Nivolumab placebo with paclitaxel followed by nivolumab placebo with anthracycline + cyclophosphamide as neoadjuvant (pre-surgery) treatment, then nivolumab placebo with adjuvant (post-surgery) endocrine therapy of investigator's choice
Drug: paclitaxel (PTX)
Specified dose on Specified days

Other: nivolumab placebo
Specified dose on Specified days

Drug: anthracycline
Specified dose on Specified days

Drug: cyclophosphamide
Specified dose on Specified days

Drug: Endocrine Therapy
Variable endocrine therapy of investigators choice

Procedure: Surgery
Surgery for breast cancer
outcome measures
Primary Outcome Measures: 1. Pathological Complete response (pCR) Using the definition of ypT0/is ypN0 [ Time Frame: approximately 7 months ]
2. Event-Free Survival (EFS) [ Time Frame: up to 10 years ]
Secondary Outcome Measures: 1. Overall Survival (OS) [ Time Frame: up to 10 years ]
2. Disease-free Survival (DFS) [ Time Frame: up to 10 years ]
3. Distant Metastasis-free survival (DMFS) [ Time Frame: up to 10 years ]
4. pCR using the definition of ypT0 ypN0 [ Time Frame: approximately 7 months ]
5. pCR rate using the definition of ypT0/is [ Time Frame: approximately 7 months ]
6. Objective response rate (ORR) using definition of tumor response rate per radiologic-based assessment [ Time Frame: approximately 7 months ]
7. ORR using definition of tumor response rate per clinic-based physical assessment [ Time Frame: approximately 7 months ]
8. Residual cancer burden (RCB) category status (0, I, II, III) [ Time Frame: approximately 7 months ]
9. Incidence of adverse events (AEs) [ Time Frame: approximately 17 months ]
10. Severity of AEs [ Time Frame: approximately 17 months ]
11. Change from baseline on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) global health status/quality of life (QOL) subscale (items 29 and 30) [ Time Frame: up to 52 weeks ]
12. Change from baseline on the EORTC QLQ-C30 physical functioning subscale (items 1 to 5) [ Time Frame: up to 52 weeks ]

Eligibility Criteria
Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
Sexes Eligible for Study: All
Accepts Healthy Volunteers: No
Criteria

For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

Localized invasive breast ductal carcinoma, confirmed by the local pathologist, that includes the following combined primary tumor and clinical node (cN) categories: T1c (tumor size = 2 cm)-T2 (tumor size > 2 cm), cN1-N2 OR T3-T4, cN0-cN2. Note: Axillary lymph node status must be assessed by fine needle biopsy or core biopsy. Estrogen receptor-positive (ER+) breast cancer (BC) and with or without progesterone receptor (PgR) expression (determined on the most recently analyzed tissue sample tested locally and confirmed by the central laboratory, as defined in the relevant American Society of Clinical Oncology (ASCO)- College of American Pathologists (CAP) Guidelines. Human epidermal growth factor receptor 2 (HER2-) BC tested in the local laboratory, defined as a negative in situ hybridization test or an immunohistochemistry (IHC) status of 0, 1+, or 2+. Tumor Grade 3 of ductal histology, Or Tumor Grade 2 of ductal histology having an ER expression level percentage between 1-10% Must agree to provide primary breast tumor tissue at baseline and at surgery Must be deemed eligible for surgery Males and females must agree to follow specific methods of contraception, if applicable, while participating in the trial Must have an Eastern Cooperative Oncology Group (ECOG) scale performance status of 0 or 1

Exclusion Criteria:

Breastfeeding, pregnant, or expecting to conceive or father children within the projected duration of the study, starting with the screening through 12 months for participants who receive cyclophosphamide, or 6 months for participants who do not receive cyclophosphamide, after the last dose of study treatment Prior treatment with chemotherapy, endocrine therapy (ET), targeted therapy, and/or radiation therapy for the currently diagnosed breast cancer prior to enrollment Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways Significant cardiovascular disease such as left ventricular ejection fraction (LVEF) 1 tumor in different quadrants of the breast) Bilateral invasive BC

Other protocol-defined inclusion/exclusion criteria apply


Contacts and Locations
Contacts

Contact: Recruiting sites have contact information.Please contact the sites directly. If there is no contact information, please email: Clinical.Trials@bms.com

Contact: First line of the email MUST contain NCT # and Site #.

Locations
United States, Alabama University of South Alabama Mitchell Cancer Institute Mobile
United States, California Local Institution Concord
United States, California Local Institution Duarte
United States, California Marin Cancer Care, Inc Greenbrae
United States, California Local Institution Los Angeles
United States, California Local Institution Orange
United States, California Innovative Clinical Research Institute Whittier
United States, Connecticut Bennett Cancer Center Stamford
United States, Florida Cancer Specialists of North FL Jacksonville
United States, Florida University of Miami Miami
United States, Florida Local Institution Orlando
United States, Florida Sacred Heart Medical Group Pensacola
United States, Florida Tallahassee Memorial Cancer Center Tallahassee
United States, Georgia University Cancer Blood Ctr Athens
United States, Georgia Northside Hospital,Inc.- Central Research Department Atlanta
United States, Georgia John B. Amos Cancer Center Columbus
United States, Illinois Northwestern Memorial Hospital Chicago
United States, Indiana Fort Wayne Medical Oncology and Hematology, Inc. Fort Wayne
United States, Kentucky Local Institution Louisville
United States, Maine New England Cancer Specialists Scarborough
United States, Maryland American Oncology Partners of Maryland, PA Bethesda
United States, Missouri HCA Midwest Division Kansas City
United States, New Jersey Local Institution Flemington
United States, New Jersey Summit Medical Group Florham Park
United States, New Jersey The Cancer Center At Hackensack University Medical Center Hackensack
United States, New Jersey Rutgers Cancer Institute of New Jersey New Brunswick
United States, New Mexico University of New Mexico Comprehensive Cancer Center Albuquerque
United States, New York Montefiore Medical Center Bronx
United States, North Carolina Local Institution Charlotte
United States, North Carolina Local Institution Durham
United States, North Carolina Local Institution Winston-Salem
United States, Ohio Local Institution Canton
United States, Ohio Local Institution Cincinnati
United States, Ohio MetroHealth Medical Center Cleveland
United States, Ohio Local Institution Cleveland
United States, Oregon Local Institution Portland
United States, Tennessee Tennessee Oncology, PLLC - SCRI - PPDS Chattanooga
United States, Tennessee Local Institution Knoxville
United States, Texas Ft. Worth Center For Cancer Blood Disorders Fort Worth
United States, Utah Local Institution Salt Lake City
United States, Virginia Local Institution Fairfax
United States, Virginia Hematology-Oncology Associates Of Fredricksburg, Inc Fredericksburg
United States, Virginia Virginia Cancer Institute Richmond
United States, Washington Local Institution Seattle
Argentina, Buenos Aires Local Institution Caba
Argentina, Buenos Aires Local Institution Ciudad Autonoma Beunos Aires
Argentina, Buenos Aires Hospital Britanico De Buenos Aires Ciudad Autónoma de Buenos Aires
Argentina, Buenos Aires Local Institution La Plata
Argentina, Cordoba Local Institution Río Cuarto
Argentina, Santa FE Local Institution Rosario
Argentina Clinica Adventista Belgrano Buenos Aires
Argentina Instituto Medico Especialazado Alexander Fleming Caba
Argentina Local Institution Cordoba
Argentina Local Institution Cordoba
Argentina Local Institution La Rioja
Argentina Local Institution Viedma
Australia, New South Wales Mater Hospital North Sydney
Australia, New South Wales Port Macquarie Base Hospital Port Macquarie
Australia, New South Wales Local Institution Sydney
Australia, Queensland Royal Brisbane and Womens Hospital Herston
Australia, South Australia Calvary Central Districts Hospital Elizabeth Vale
Australia, Victoria Monash Medical Centre Clayton Clayton
Australia, Victoria Austin Hospital Heidelberg
Australia, Victoria Peter MacCallum Cancer Centre Melbourne
Australia, Victoria Ballarat Base Hospital North Ballarat
Austria Universitaetsklinik F. Frauenheilkunde / Geburtshilfe Graz
Austria Med. Universitaet Innsbruck Innsbruck
Austria Landeskrankenhaus-Universitaetsklinik fuer Innere Medizin III Salzburg
Austria Medizinische Universitaet Wien Wien
Austria Medizinische Universitaet Wien Wien
Belgium Local Institution Charleroi
Belgium Universitair Ziekenhuis Antwerpen Edegem
Belgium UZ Gent-Medical oncology Gent
Belgium Universitair Ziekenhuis Brussel - PIN Jette
Belgium CHU de Liège Liege
Brazil, Ceara Oncocentro Servico Medicos e Hospitalares Ltda Fortaleza
Brazil, Distrito Federal Hospital Sirio Libanes Brasilia
Brazil, Goias Local Institution Goiania
Brazil, Minas Gerais Universidade Federal De Minas Gerais Belo Horizonte - Mg
Brazil, Minas Gerais Local Institution Juiz de Fora
Brazil, RIO Grande DO SUL ONCOSITE - Centro de Pesquisa Clinica em Oncologia Ijui
Brazil, RIO Grande DO SUL Irmandade da Santa Casa de Misericordia de Porto Alegre - Hospital Santa Rita Port Alegre
Brazil, RIO Grande DO SUL Local Institution Porto Alegre
Brazil, Rio Grande Do Sul Hospital Sao Lucas Da Pucrs Porto Alegre
Brazil, RIO Grande DO SUL Local Institution Santa Cruz do Sul
Brazil, Sao Paulo Fundacao Pio Xii Hosp Cancer De Barretos Barretos
Brazil, SAO Paulo Faculdade de Medicina do ABC Santo Andre
Brazil, SAO Paulo Local Institution São Paulo
Brazil COI Clinicas Oncologicas Integradas SA Rio de Janeiro
Brazil Centro de Pesquisa e Centro de Estudos em Oncologia Ginecologica e Mamaria Sao Paulo
Brazil Hospital Municipal Vila Santa Catarina Sao Paulo
Canada, Nova Scotia Local Institution Halifax
Canada, Ontario Local Institution Thunder Bay
Canada, Ontario Local Institution Toronto
Canada, Ontario Local Institution Toronto
Canada, Quebec Local Institution Montreal
Canada, Quebec Local Institution Montreal
Canada, Quebec Centre Hospitalier de l'Université de Montréal-Breast Cancer Montréal
Canada, Quebec Centre integre universitaire de sante et de service sociaux de l'estrie - CHUS Sherbrooke
Chile, Coquimbo Local Institution La Serena
Chile, Metropolitana Centro de Investigacion Clinica Bradford Hill Santiago de Chile
Chile, Metropolitana Hospital Clinico Pontificia Universidad Catolica De Chile Santiago Region Metropolitana
Chile, Valparaiso Oncocentro Apys Vina del Mar
China, Anhui Local Institution Bengbu
China, Anhui Local Institution Hefei
China, Beijing Local Institution Beijing
China, Beijing Local Institution Beijing
China, Chongqing Local Institution Chongqing
China, Guangdong Local Institution Guangzhou
China, Guangdong Local Institution Guangzhou
China, Guangdong Local Institution Guangzhou
China, Hebei Local Institution Shjiazhuang
China, Heilongjiang Local Institution Harbin
China, Henan Local Institution Zhengzhou
China, Hubei Local Institution Wuhan
China, Jilin Local Institution Changchun
China, Jilin Local Institution Changchun
China, Liaoning Local Institution Shenyang
China, Shan1xi Local Institution XiAn
China, Shandong Local Institution Jinan
China, Shandong Local Institution Qingdao
China, Shandong Local Institution YanTai
China, Shanghai Local Institution Shanghai
China, Sichuan Local Institution Chengdu
China, Tianjin Local Institution Tianjin
China, Xinjiang Local Institution Urumqi
China, Zhejiang Local Institution Hangzhou
China, Zhejiang Local Institution Hangzhou
China, Zhejiang Local Institution Hangzhou
China Local Institution Chengdu
China Local Institution Xiamen
Colombia, Bogota Local Institution Colombia
Colombia Local Institution Barranquilla
Colombia Local Institution Bogotá
Colombia Local Institution Cali
Colombia Local Institution Floridablanca
Colombia Local Institution Monteria
Colombia Local Institution Pereira
Colombia Local Institution Rionegro, Antioquia
Czechia Local Institution Chomutov
Czechia Klinika onkologie a radioterapie Hradec Kralove
Czechia Komplexni onkologicke centrum Novy Jicin
Czechia Onkologicka klinika Olomouc
Czechia Radioterapeuticka a onkologicka klinika FNKV Praha 10
Denmark Local Institution Aarhus N
Denmark Local Institution Herlev
Denmark Local Institution Kobenhavn O
Denmark Local Institution Naestved
Finland Local Institution Helsinki
Finland Local Institution Tampere
France Local Institution Bayonne
France Chu Jean Minjoz Besancon
France Hopital Morvan Brest
France Centre Jean Perrin Clermont-ferrand
France Clinique Victor Hugo Le Mans
France Hopital Prive Jean Mermoz Lyon
France Institut du Cancer de Montpellier Montpellier Cedex 5
France Hopital Europeen Georges Pompidou Paris
France Hôpital Privé Des Côtes d'Armor Plerin
France Institut De Cancerologie De L Ouest Saint Herblain Cedex
France Clinique Sainte Anne Strasbourg
France Centre Hospitalier intercommunal de Toulon La Seyne sur Mer Toulon
France Institut Gustave Roussy Villejuif
Germany Helios Klinikum Berlin-Buch Berlin
Germany Local Institution Berlin
Germany Universitaetsklinikum Carl Gustav Carus Dresden
Germany Local Institution Erlangen
Germany Universitaetsklinikum Essen Essen
Germany Universitatsklinikum Frankfurt Frankfurt
Germany Agaplesion Diakonieklinikum Hamburg
Germany Universitaetsklinik Heidelberg Heidelberg
Germany Universitaetsklinikum d. Saarlandes Homburg
Germany Universitaetsklinikum Koeln Koeln
Germany Universitatsklinikum Leipzig Leipzig
Germany Evang. Krankenhaus Bethesda Moenchengladbach
Germany LMU Klinikum der Universität München Muenchen
Germany Uni Frauenklinikum Suedstadt Rostock
Germany CaritasKlinikum Saarbruecken. Saarbruecken
Germany MVZ-Onkologie Velbert GbR Velbert
Germany Universitaetsklinikum Wuerzburg Würzburg
Hong Kong Local Institution Hong Kong
Ireland, Dublin St. James'S Hospital Dublin 8
Ireland Cork University Hospital Cork
Ireland Beaumont Hospital Dublin
Italy Local Institution Bergamo
Italy Local Institution Brindisi
Italy Local Institution Catania
Italy Azienda Ospedaliero-Universitaria Mater Domini Catanzaro
Italy Local Institution Milano
Italy Azienda Ospedaliero Universitaria Federico II di Napoli Napoli
Italy Istituto Nazionale Tumori Fondazione Pascale Napoli
Italy Istituto Oncologico Veneto IOV Padova
Italy Fondazione Irccs - Policlinico San Matteo Pavia
Italy Local Institution Prato
Italy Local Institution Roma
Italy Istituto Clinico Humanitas Rozzano (MI)
Korea, Republic of Local Institution Seoul
Korea, Republic of Local Institution Seoul
Korea, Republic of Local Institution Seoul
Korea, Republic of Local Institution Seoul
Mexico, BAJA California Local Institution Tijuana
Mexico, Distrito Federal Local Institution Mexico City
Mexico, Distrito Federal Local Institution Tlalpan
Mexico, Nuevo LEON Local Institution Monterrey
Mexico, Yucatan Local Institution Merida
Mexico Local Institution Campeche
Mexico Local Institution Chihuahua
Mexico Local Institution Colima
Mexico Local Institution Oaxaca
Netherlands Antoni Van Leeuwenhoek Ziekenhuis Amsterdam
Netherlands Amphia Ziekenhuis Breda
Netherlands Deventer Ziekenhuis Deventer
Netherlands Local Institution Rotterdam
Netherlands Universitair Medisch Centrum Utrecht Utrecht
Poland Oddzial Dzienny Chemioterapii Koszalin
Poland Local Institution Krakow
Poland Klinika Onkologii CZMP Lodz
Poland Local Institution Opole
Poland Klinika Nowotworow Piersi i Chirurgii Rekonstrukcyjnej Warszawa
Portugal Local Institution Lisboa
Portugal Local Institution Lisboa
Portugal Local Institution Porto
Puerto Rico Ponce Medical School Foundation Ponce
Puerto Rico Local Institution San Juan
Romania Local Institution Bucharest
Romania Local Institution Bucharest
Romania Local Institution Bucuresti
Romania Local Institution Craiova
Romania Local Institution Floresti
Romania Local Institution Suceava
Russian Federation Local Institution Krasnodar
Russian Federation Local Institution Moscow
Russian Federation Local Institution Moscow
Russian Federation Local Institution Moskva
Russian Federation Local Institution Ryazan
Russian Federation Local Institution Saint Petersburg
Russian Federation Local Institution Sankt-Peterburg
Russian Federation Local Institution Sochi
Singapore Local Institution Singapore
Singapore Local Institution Singapore
Singapore Local Institution Singapore
Spain Local Institution Barcelona
Spain Local Institution Barcelona
Spain Local Institution Elche (alicante)
Spain Local Institution Madrid
Spain Local Institution Madrid
Spain Local Institution Madrid
Spain Local Institution Malaga
Spain Local Institution Santiago Compostela
Spain Local Institution Sevilla
Switzerland University Hospital Basel Basel
Switzerland CHUV Lausanne
Switzerland Onkologiezentrum Thun-Berner Oberland Spital Sts Ag Thun
Taiwan Local Institution Kaohsiung
Taiwan Local Institution Tainan
Taiwan Local Institution Tainan
Taiwan Local Institution Taipei
Taiwan Local Institution Taipei
Turkey Local Institution Adana
Turkey Local Institution Ankara
Turkey Local Institution Antalya
Turkey Local Institution Istanbul
United Kingdom, Glamorgan Local Institution Swansea
United Kingdom, Manchester The Christie NHS Foundation Trust Withington
United Kingdom Local Institution Coventry
United Kingdom Local Institution Headington
United Kingdom Local Institution London
Sponsors and Collaborators
Bristol-Myers Squibb
Investigator
Study Director : Bristol-Myers Squibb Bristol-Myers Squibb
More Information
Responsible Party : Bristol-Myers Squibb
ClinicalTrials.gov Identifier : NCT04109066     
Other Study ID Numbers : CA209-7FL
First Posted : September 30, 2019
Last Update Posted : December 2, 2021
Last Verified : December 2021
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Bristol-Myers Squibb: Nivolumab
Breast Cancer
Cancer
Estrogen Receptor-Positive (ER+)
Human Epidermal Growth Factor 2 Negative (HER2-)
Neoadjuvant
Adjuvant
Primary Breast Cancer
Additional relevant MeSH terms :
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases