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 Active, not recruiting September 30, 2019 July 22, 2022

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 : 506 participants
Allocation : Randomized
Intervention Model : Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: 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
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. Residual cancer burden (RCB) category status (0, I, II, III) [ Time Frame: approximately 7 months ]
2. Incidence of adverse events (AEs) [ Time Frame: approximately 17 months ]
3. Severity of AEs [ Time Frame: approximately 17 months ]
4. ORR using definition of tumor response rate per clinic-based physical assessment [ Time Frame: approximately 7 months ]
5. Overall Survival (OS) [ Time Frame: up to 10 years ]
6. Disease-free Survival (DFS) [ Time Frame: up to 10 years ]
7. Distant Metastasis-free survival (DMFS) [ Time Frame: up to 10 years ]
8. pCR using the definition of ypT0 ypN0 [ Time Frame: approximately 7 months ]
9. pCR rate using the definition of ypT0/is [ Time Frame: approximately 7 months ]
10. Objective response rate (ORR) using definition of tumor response rate per radiologic-based assessment [ Time Frame: approximately 7 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

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
Locations
Colombia, Bogota Local Institution Colombia
Colombia Local Institution Rionegro, Antioquia
Colombia, Distrito Capital De Bogotá Local Institution - 0094 Bogotá
Colombia, Santander Local Institution - 0098 Piedecuesta
Colombia Local Institution - 0261 Barranquilla
Colombia Local Institution - 0093 Cali
Colombia Local Institution - 0113 Monteria
Colombia Local Institution Pereira
United States, Alabama Local Institution - 0136 Mobile
United States, California Local Institution - 0052 Greenbrae
United States, California Local Institution - 0051 Whittier
United States, Connecticut Local Institution - 0182 Stamford
United States, Florida Local Institution - 0150 Jacksonville
United States, Florida Local Institution - 0097 Miami
United States, Florida Local Institution - 0149 Pensacola
United States, Florida Local Institution - 0120 Tallahassee
United States, Georgia Local Institution - 0054 Athens
United States, Georgia Local Institution - 0107 Atlanta
United States, Georgia Local Institution - 0056 Columbus
United States, Illinois Local Institution - 0221 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 Topsham
United States, Maryland American Oncology Partners of Maryland, PA Bethesda
United States, Missouri HCA Midwest Division Kansas City
United States, New Jersey Local Institution - 0109 Florham Park
United States, New Jersey Local Institution - 0050 Hackensack
United States, New Jersey Rutgers Cancer Institute of New Jersey New Brunswick
United States, New Mexico Local Institution - 0181 Albuquerque
United States, New York Local Institution - 0041 Bronx
United States, North Carolina Local Institution - 0283 Charlotte
United States, North Carolina Duke Cancer Institute Durham
United States, North Carolina Local Institution Winston-Salem
United States, Ohio Local Institution - 0053 Cleveland
United States, Tennessee Local Institution - 0218 Chattanooga
United States, Texas Local Institution - 0121 Fort Worth
United States, Virginia Local Institution - 0224 Fairfax
United States, Virginia Local Institution - 0122 Fredericksburg
United States, Virginia Virginia Cancer Institute Richmond
United States, Washington Local Institution - 0274 Seattle
Argentina, Buenos Aires Local Institution - 0020 Caba
Argentina, Buenos Aires Local Institution Ciudad Autonoma Beunos Aires
Argentina, Buenos Aires Local Institution - 0015 La Plata
Argentina, Cordoba Local Institution - 0303 Río Cuarto
Argentina, Distrito Federal Local Institution Buenos Aires
Argentina, Distrito Federal Local Institution - 0008 Capital Federal
Argentina, Distrito Federal Local Institution - 0013 Ciudad Autonoma de Buenos Aires
Argentina, Santa FE Local Institution Rosario
Argentina Clinica Adventista Belgrano Buenos Aires
Argentina Local Institution - 0021 Cordoba
Argentina Local Institution Cordoba
Argentina Local Institution La Rioja
Argentina Local Institution Viedma
Australia, New South Wales Local Institution Darlinghurst
Australia, New South Wales Local Institution - 0071 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 Local Institution Franskton
Australia, Victoria Austin Hospital Heidelberg
Australia, Victoria Local Institution - 0070 Melbourne
Australia, Victoria Local Institution - 0068 North Ballarat
Australia, Western Australia Local Institution Perth
Austria Local Institution - 0045 Graz
Austria Local Institution - 0042 Innsbruck
Austria Local Institution - 0048 Salzburg
Austria Local Institution - 0046 Wien
Austria Local Institution - 0047 Wien
Belgium Local Institution - 0187 Brussels
Belgium Local Institution - 0030 Charleroi
Belgium Local Institution - 0037 Edegem
Belgium Local Institution - 0032 Gent
Belgium Local Institution - 0031 Liege
Brazil, Ceara Local Institution - 0130 Fortaleza
Brazil, Distrito Federal Local Institution - 0225 Brasilia
Brazil, Goias Local Institution - 0287 Goiânia
Brazil, Minas Gerais Local Institution - 0133 Belo Horizonte
Brazil, RIO Grande DO SUL Local Institution - 0132 Ijui
Brazil, RIO Grande DO SUL Local Institution - 0288 Porto Alegre
Brazil, Rio Grande Do Sul Local Institution - 0131 Porto Alegre
Brazil, RIO Grande DO SUL Local Institution - 0135 Porto Alegre
Brazil, RIO Grande DO SUL Local Institution - 0273 Santa Cruz do Sul
Brazil, SAO Paulo Local Institution - 0134 Barretos
Brazil, SAO Paulo Local Institution - 0128 Santo Andre
Brazil, SAO Paulo Local Institution - 0272 São Paulo
Brazil Local Institution - 0129 Rio de Janeiro
Brazil Local Institution - 0144 São Paulo
Brazil Local Institution - 0104 São Paulo
Canada, Nova Scotia Local Institution Halifax
Canada, Ontario Local Institution Oshawa
Canada, Ontario Local Institution Ottawa
Canada, Ontario Local Institution Thunder Bay
Canada, Ontario Local Institution Toronto
Canada, Ontario Local Institution Toronto
Canada, Quebec Local Institution Montreal
Canada, Quebec Centre Hospitalier de l'Université de Montréal-Breast Cancer Montréal
Canada, Quebec Local Institution - 0058 Sherbrooke
Chile, Coquimbo Local Institution - 0197 La Serena
Chile, Metropolitana Local Institution - 0016 Santiago de Chile
Chile, Metropolitana Local Institution - 0019 Santiago Region Metropolitana
Chile, Metropolitana Local Institution - 0318 Santiago
Chile, Valparaiso Local Institution - 0018 Vina del Mar
Chile Local Institution - 0326 Antofagasta
China, Anhui Local Institution - 0235 Bengbu
China, Anhui Local Institution - 0239 Hefei
China, Beijing Local Institution Beijing
China, Beijing Local Institution - 0215 Beijing
China, Chongqing Local Institution - 0319 Chongqing
China, Chongqing Local Institution - 0232 Chongqing
China, Guangdong Local Institution - 0267 Guangzhou
China, Guangdong Local Institution - 0241 Guangzhou
China, Guangdong Local Institution Guangzhou
China, Guizhou Local Institution - 0312 Zunyi
China, Hebei Local Institution - 0240 Shjiazhuang
China, Hebei Local Institution - 0250 Wuhan
China, Heilongjiang Local Institution - 0248 Harbin
China, Henan Local Institution Zhengzhou
China, Jilin Local Institution - 0255 Changchun
China, Jilin Local Institution - 0247 Changchun
China, Liaoning Local Institution Shenyang
China, Liaoning Local Institution - 0252 Shenyang
China, Shan3xi Local Institution - 0263 Xian
China, Shandong Local Institution - 0245 Jinan
China, Shandong Local Institution - 0256 Qingdao
China, Shandong Local Institution - 0214 YanTai
China, Shanghai Local Institution - 0127 Shanghai
China, Sichuan Local Institution - 0244 Chengdu
China, Tianjin Local Institution - 0254 Tianjin
China, Xinjiang Local Institution - 0311 Urumqi
China, Zhejiang Local Institution - 0238 Hangzhou
China, Zhejiang Local Institution - 0231 Hangzhou
China, Zhejiang Local Institution - 0237 Hangzhou
China Local Institution Xiamen
Czechia Klinika onkologie a radioterapie Hradec Kralove
Czechia Komplexni onkologicke centrum Novy Jicin
Czechia Onkologicka klinika Olomouc
Czechia Local Institution - 0099 Praha 10
Denmark Local Institution - 0167 Aarhus N
Denmark Local Institution - 0165 Herlev
Denmark Local Institution - 0164 Kobenhavn O
Denmark Local Institution - 0166 Naestved
Finland Local Institution - 0001 Helsinki
Finland Local Institution - 0160 Tampere
France Local Institution - 0004 Besancon
France Local Institution - 0024 Brest
France Centre Jean Perrin Clermont-ferrand
France Clinique Victor Hugo Le Mans
France Hopital Prive Jean Mermoz Lyon
France Local Institution - 0152 Montpellier
France Hopital Europeen Georges Pompidou Paris
France Local Institution - 0195 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 Local Institution - 0003 Villejuif
Germany, Bayern Local Institution - 0084 München
Germany Local Institution - 0083 Berlin
Germany Local Institution - 0112 Dresden
Germany Local Institution - 0081 Essen
Germany Local Institution - 0158 Frankfurt
Germany Local Institution - 0223 Hamburg
Germany Local Institution - 0087 Heidelberg
Germany Local Institution - 0089 Homburg
Germany Local Institution - 0080 Köln
Germany Local Institution - 0196 Leipzig
Germany Local Institution - 0111 Moenchengladbach
Germany Local Institution - 0156 Rostock
Germany Local Institution - 0079 Saarbruecken
Germany Local Institution - 0157 Velbert
Germany Local Institution - 0105 Würzburg
Hong Kong Local Institution - 0115 Hong Kong
Ireland, Dublin Local Institution - 0034 Dublin 8
Ireland Cork University Hospital Cork
Ireland Local Institution Dublin
Italy Local Institution Catania
Italy Azienda Ospedaliero-Universitaria Mater Domini Catanzaro
Italy Local Institution - 0207 Milano
Italy Local Institution - 0124 Napoli
Italy Local Institution - 0183 Napoli
Italy Local Institution - 0155 Padova
Italy Local Institution - 0126 Pavia
Italy Local Institution Roma
Italy Local Institution - 0125 Rozzano (MI)
Korea, Republic of Local Institution - 0325 Seongnam
Korea, Republic of Local Institution - 0295 Seoul
Korea, Republic of Local Institution - 0320 Seoul
Korea, Republic of Local Institution - 0290 Seoul
Korea, Republic of Local Institution - 0291 Seoul
Mexico, BAJA California Local Institution - 0262 Tijuana
Mexico, Distrito Federal Local Institution - 0168 Mexico City
Mexico, Distrito Federal Local Institution - 0154 Mexico City
Mexico, Jalisco Local Institution Zapopan
Mexico, Nuevo LEON Local Institution - 0137 Monterrey
Mexico, Yucatán Local Institution - 0212 Merida
Mexico Local Institution Campeche
Mexico Local Institution - 0091 Chihuahua
Mexico Local Institution Colima
Mexico Local Institution - 0141 Oaxaca
Netherlands Antoni Van Leeuwenhoek Ziekenhuis Amsterdam
Netherlands Local Institution - 0177 Breda
Netherlands Local Institution - 0199 Deventer
Netherlands Local Institution Rotterdam
Netherlands Local Institution Utrecht
Poland Local Institution - 0335 Bydgoszcz
Poland Local Institution - 0334 Gliwice
Poland Oddzial Dzienny Chemioterapii Koszalin
Poland Local Institution Krakow
Poland Klinika Onkologii CZMP Lodz
Poland Local Institution Opole
Poland Local Institution - 0060 Warszawa
Portugal Local Institution - 0210 Lisboa
Portugal Local Institution - 0211 Lisboa
Portugal Local Institution - 0209 Porto
Puerto Rico Local Institution - 0110 Ponce
Romania Local Institution - 0029 Bucharest
Romania Local Institution Bucharest
Romania Local Institution - 0025 Bucuresti
Romania Local Institution Craiova
Romania Local Institution - 0027 Floresti
Romania Local Institution Suceava
Russian Federation Local Institution Krasnodar
Russian Federation Local Institution Moscow
Russian Federation Local Institution Moscow
Russian Federation Local Institution - 0285 Moskva
Russian Federation Local Institution Ryazan
Russian Federation Local Institution - 0284 Saint Petersburg
Russian Federation Local Institution - 0306 Sankt-Peterburg
Russian Federation Local Institution Sochi
Singapore Local Institution - 0078 Singapore
Singapore Local Institution - 0076 Singapore
Singapore Local Institution - 0077 Singapore
Spain Local Institution - 0171 Barcelona
Spain Local Institution - 0172 Barcelona
Spain Local Institution - 0205 Elche (Alicante)
Spain Local Institution - 0173 Madrid
Spain Local Institution - 0176 Madrid
Spain Local Institution - 0169 Malaga
Spain Local Institution - 0204 Pamplona
Spain Local Institution - 0174 Santiago de Compostela
Spain Local Institution - 0170 Sevilla
Switzerland Local Institution - 0184 Basel
Switzerland CHUV Lausanne
Switzerland Local Institution - 0185 Thun
Taiwan Local Institution - 0301 Kaohsiung
Taiwan Local Institution - 0300 Tainan City
Taiwan Local Institution - 0298 Tainan
Taiwan Local Institution - 0305 Taipei
Taiwan Local Institution - 0297 Taipei
Turkey Local Institution - 0073 Adana
Turkey Local Institution Ankara
Turkey Local Institution Antalya
Turkey Local Institution Istanbul
United Kingdom, Manchester Local Institution - 0006 Withington
United Kingdom Local Institution - 0005 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 : July 22, 2022
Last Verified : July 2022
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 :
Neoplasms
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases