Trial Review

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04109066




Registration number
NCT04109066
Ethics application status
Date submitted
27/09/2019
Date registered
30/09/2019
Date last updated
12/03/2024

Titles & IDs
Public 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
Scientific 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
Secondary ID [1] 0 0
CA209-7FL
Universal Trial Number (UTN)
Trial acronym
CheckMate 7FL
Linked study record

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

Intervention/exposure
Study type
Interventional(has expanded access)
Description of intervention(s) / exposure
Treatment: Other - nivolumab
Treatment: Drugs - paclitaxel (PTX)
Other interventions - nivolumab placebo
Treatment: Drugs - anthracycline
Treatment: Drugs - cyclophosphamide
Treatment: Drugs - Endocrine Therapy
Treatment: Surgery - Surgery

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

Placebo comparator: Arm B: Placebo combined with neoadjuvant CT and then adjuvant ET - Nivolumab placebo with paclitaxel followed by nivolumab placebo with anthracycline + cyclophosphamide as neoadjuvant (pre-surgery) treatment, then adjuvant (post-surgery) endocrine therapy of investigator's choice


Treatment: Other: nivolumab
Specified Dose on Specified days

Treatment: Drugs: paclitaxel (PTX)
Specified dose on Specified days

Other interventions: nivolumab placebo
Specified dose on Specified days

Treatment: Drugs: anthracycline
Specified dose on Specified days

Treatment: Drugs: cyclophosphamide
Specified dose on Specified days

Treatment: Drugs: Endocrine Therapy
Variable endocrine therapy of investigators choice

Treatment: Surgery: Surgery
Surgery for breast cancer
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Drugs
Intervention code [3] 0 0
Other interventions
Intervention code [4] 0 0
Treatment: Surgery
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Pathological Complete Response (pCR) Rate
Timepoint [1] 0 0
Up to approximately 37 months
Secondary outcome [1] 0 0
Pathological Complete Response (pCR) Rate (PD-L1 >=1%)
Timepoint [1] 0 0
Up to approximately 37 months
Secondary outcome [2] 0 0
Number of Participants With Residual Cancer Burden (RCB)
Timepoint [2] 0 0
Up to approximately 37 months
Secondary outcome [3] 0 0
Number of Participants With Residual Cancer Burden (RCB) PD-L1 >=1%
Timepoint [3] 0 0
Up to approximately 37 months
Secondary outcome [4] 0 0
Number of Participants With Adverse Events (AEs)
Timepoint [4] 0 0
From first dose to 30 days post last dose of neoadjuvant or adjuvant study therapy (Up to approximately 25 months)
Secondary outcome [5] 0 0
Number of Participants With Serious Adverse Events (SAEs)
Timepoint [5] 0 0
From first dose to 30 days post last dose of neoadjuvant or adjuvant study therapy (Up to approximately 25 months)
Secondary outcome [6] 0 0
Number of Participants Who Died
Timepoint [6] 0 0
Up to approximately 37 months

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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) < 50% at baseline as assessed by echocardiography (ECHO) or multigated acquisition (MUGA) scan performed at screening, or Class III or IV myocardial disease as described by the New York Heart Association
* History of ipsilateral invasive BC, regardless of treatment, ipsilateral ductal carcinoma in situ treated with radiation, or contralateral invasive BC, at any time
* Definitive clinical or radiologic evidence of metastatic disease
* Multicentric BC (the presence of > 1 tumor in different quadrants of the breast)
* Bilateral invasive BC

Other protocol-defined inclusion/exclusion criteria apply

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
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
20/11/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
27/12/2023
Sample size
Target
Accrual to date
Final
521
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
Local Institution - 0071 - North Sydney
Recruitment hospital [2] 0 0
Local Institution - 0069 - Port Macquarie
Recruitment hospital [3] 0 0
Local Institution - 0072 - Herston
Recruitment hospital [4] 0 0
Local Institution - 0067 - Elizabeth Vale
Recruitment hospital [5] 0 0
Local Institution - 0066 - Clayton
Recruitment hospital [6] 0 0
Local Institution - 0142 - Clayton
Recruitment hospital [7] 0 0
Local Institution - 0070 - Melbourne
Recruitment hospital [8] 0 0
Local Institution - 0068 - North Ballarat
Recruitment postcode(s) [1] 0 0
2060 - North Sydney
Recruitment postcode(s) [2] 0 0
2444 - Port Macquarie
Recruitment postcode(s) [3] 0 0
4029 - Herston
Recruitment postcode(s) [4] 0 0
5112 - Elizabeth Vale
Recruitment postcode(s) [5] 0 0
3168 - Clayton
Recruitment postcode(s) [6] 0 0
3000 - Melbourne
Recruitment postcode(s) [7] 0 0
33500 - North Ballarat
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Indiana
Country [8] 0 0
United States of America
State/province [8] 0 0
Maine
Country [9] 0 0
United States of America
State/province [9] 0 0
Maryland
Country [10] 0 0
United States of America
State/province [10] 0 0
Missouri
Country [11] 0 0
United States of America
State/province [11] 0 0
New Jersey
Country [12] 0 0
United States of America
State/province [12] 0 0
New Mexico
Country [13] 0 0
United States of America
State/province [13] 0 0
New York
Country [14] 0 0
United States of America
State/province [14] 0 0
North Carolina
Country [15] 0 0
United States of America
State/province [15] 0 0
Ohio
Country [16] 0 0
United States of America
State/province [16] 0 0
Tennessee
Country [17] 0 0
United States of America
State/province [17] 0 0
Texas
Country [18] 0 0
United States of America
State/province [18] 0 0
Virginia
Country [19] 0 0
United States of America
State/province [19] 0 0
Washington
Country [20] 0 0
Argentina
State/province [20] 0 0
Buenos Aires
Country [21] 0 0
Argentina
State/province [21] 0 0
Ciudad Autónoma De Buenos Aires
Country [22] 0 0
Argentina
State/province [22] 0 0
Cordoba
Country [23] 0 0
Argentina
State/province [23] 0 0
Distrito Federal
Country [24] 0 0
Argentina
State/province [24] 0 0
Santa FE
Country [25] 0 0
Argentina
State/province [25] 0 0
La Rioja
Country [26] 0 0
Argentina
State/province [26] 0 0
Viedma
Country [27] 0 0
Austria
State/province [27] 0 0
Graz
Country [28] 0 0
Austria
State/province [28] 0 0
Innsbruck
Country [29] 0 0
Austria
State/province [29] 0 0
Salzburg
Country [30] 0 0
Austria
State/province [30] 0 0
Wien
Country [31] 0 0
Belgium
State/province [31] 0 0
Brussels
Country [32] 0 0
Belgium
State/province [32] 0 0
Charleroi
Country [33] 0 0
Belgium
State/province [33] 0 0
Edegem
Country [34] 0 0
Belgium
State/province [34] 0 0
Gent
Country [35] 0 0
Belgium
State/province [35] 0 0
Liege
Country [36] 0 0
Brazil
State/province [36] 0 0
Ceara
Country [37] 0 0
Brazil
State/province [37] 0 0
Distrito Federal
Country [38] 0 0
Brazil
State/province [38] 0 0
Goias
Country [39] 0 0
Brazil
State/province [39] 0 0
Minas Gerais
Country [40] 0 0
Brazil
State/province [40] 0 0
RIO Grande DO SUL
Country [41] 0 0
Brazil
State/province [41] 0 0
Rio Grande Do Sul
Country [42] 0 0
Brazil
State/province [42] 0 0
SAO Paulo
Country [43] 0 0
Brazil
State/province [43] 0 0
São Paulo
Country [44] 0 0
Brazil
State/province [44] 0 0
Rio de Janeiro
Country [45] 0 0
Canada
State/province [45] 0 0
Quebec
Country [46] 0 0
Chile
State/province [46] 0 0
Coquimbo
Country [47] 0 0
Chile
State/province [47] 0 0
Metropolitana
Country [48] 0 0
Chile
State/province [48] 0 0
Valparaiso
Country [49] 0 0
Chile
State/province [49] 0 0
Antofagasta
Country [50] 0 0
China
State/province [50] 0 0
Anhui
Country [51] 0 0
China
State/province [51] 0 0
Beijing
Country [52] 0 0
China
State/province [52] 0 0
Chongqing
Country [53] 0 0
China
State/province [53] 0 0
Guangdong
Country [54] 0 0
China
State/province [54] 0 0
Guizhou
Country [55] 0 0
China
State/province [55] 0 0
Hebei
Country [56] 0 0
China
State/province [56] 0 0
Heilongjiang
Country [57] 0 0
China
State/province [57] 0 0
Henan
Country [58] 0 0
China
State/province [58] 0 0
Jilin
Country [59] 0 0
China
State/province [59] 0 0
Liaoning
Country [60] 0 0
China
State/province [60] 0 0
Shan3xi
Country [61] 0 0
China
State/province [61] 0 0
Shandong
Country [62] 0 0
China
State/province [62] 0 0
Shanghai
Country [63] 0 0
China
State/province [63] 0 0
Sichuan
Country [64] 0 0
China
State/province [64] 0 0
Tianjin
Country [65] 0 0
China
State/province [65] 0 0
Xinjiang
Country [66] 0 0
China
State/province [66] 0 0
Zhejiang
Country [67] 0 0
Colombia
State/province [67] 0 0
Atlántico
Country [68] 0 0
Colombia
State/province [68] 0 0
Bogota
Country [69] 0 0
Colombia
State/province [69] 0 0
Córdoba
Country [70] 0 0
Colombia
State/province [70] 0 0
Distrito Capital De Bogotá
Country [71] 0 0
Colombia
State/province [71] 0 0
Santander
Country [72] 0 0
Colombia
State/province [72] 0 0
Cali
Country [73] 0 0
Colombia
State/province [73] 0 0
Pereira
Country [74] 0 0
Colombia
State/province [74] 0 0
Rionegro
Country [75] 0 0
Czechia
State/province [75] 0 0
Hradec Kralove
Country [76] 0 0
Czechia
State/province [76] 0 0
Novy Jicin
Country [77] 0 0
Czechia
State/province [77] 0 0
Olomouc
Country [78] 0 0
Czechia
State/province [78] 0 0
Praha 10
Country [79] 0 0
Denmark
State/province [79] 0 0
Aarhus N
Country [80] 0 0
Denmark
State/province [80] 0 0
Herlev
Country [81] 0 0
Denmark
State/province [81] 0 0
Kobenhavn O
Country [82] 0 0
Denmark
State/province [82] 0 0
Naestved
Country [83] 0 0
Finland
State/province [83] 0 0
Helsinki
Country [84] 0 0
Finland
State/province [84] 0 0
Tampere
Country [85] 0 0
France
State/province [85] 0 0
Sarthe
Country [86] 0 0
France
State/province [86] 0 0
Besancon
Country [87] 0 0
France
State/province [87] 0 0
Brest
Country [88] 0 0
France
State/province [88] 0 0
Clermont-Ferrand
Country [89] 0 0
France
State/province [89] 0 0
Lyon
Country [90] 0 0
France
State/province [90] 0 0
Montpellier
Country [91] 0 0
France
State/province [91] 0 0
Paris
Country [92] 0 0
France
State/province [92] 0 0
Plerin
Country [93] 0 0
France
State/province [93] 0 0
Saint Herblain
Country [94] 0 0
France
State/province [94] 0 0
Strasbourg
Country [95] 0 0
France
State/province [95] 0 0
Toulon Cedex
Country [96] 0 0
France
State/province [96] 0 0
Villejuif
Country [97] 0 0
Germany
State/province [97] 0 0
Bayern
Country [98] 0 0
Germany
State/province [98] 0 0
Saarland
Country [99] 0 0
Germany
State/province [99] 0 0
Berlin
Country [100] 0 0
Germany
State/province [100] 0 0
Dresden
Country [101] 0 0
Germany
State/province [101] 0 0
Essen
Country [102] 0 0
Germany
State/province [102] 0 0
Frankfurt
Country [103] 0 0
Germany
State/province [103] 0 0
Hamburg
Country [104] 0 0
Germany
State/province [104] 0 0
Heidelberg
Country [105] 0 0
Germany
State/province [105] 0 0
Homburg
Country [106] 0 0
Germany
State/province [106] 0 0
Köln
Country [107] 0 0
Germany
State/province [107] 0 0
Leipzig
Country [108] 0 0
Germany
State/province [108] 0 0
Moenchengladbach
Country [109] 0 0
Germany
State/province [109] 0 0
Rostock
Country [110] 0 0
Germany
State/province [110] 0 0
Velbert
Country [111] 0 0
Germany
State/province [111] 0 0
Würzburg
Country [112] 0 0
Hong Kong
State/province [112] 0 0
Hong Kong
Country [113] 0 0
Ireland
State/province [113] 0 0
Dublin
Country [114] 0 0
Ireland
State/province [114] 0 0
Beaumont
Country [115] 0 0
Ireland
State/province [115] 0 0
Cork
Country [116] 0 0
Italy
State/province [116] 0 0
Catanzaro
Country [117] 0 0
Italy
State/province [117] 0 0
Milano
Country [118] 0 0
Italy
State/province [118] 0 0
Napoli
Country [119] 0 0
Italy
State/province [119] 0 0
Padova
Country [120] 0 0
Italy
State/province [120] 0 0
Pavia
Country [121] 0 0
Italy
State/province [121] 0 0
Roma
Country [122] 0 0
Italy
State/province [122] 0 0
Rozzano (MI)
Country [123] 0 0
Korea, Republic of
State/province [123] 0 0
Seongnam
Country [124] 0 0
Korea, Republic of
State/province [124] 0 0
Seoul
Country [125] 0 0
Mexico
State/province [125] 0 0
BAJA California
Country [126] 0 0
Mexico
State/province [126] 0 0
Distrito Federal
Country [127] 0 0
Mexico
State/province [127] 0 0
Jalisco
Country [128] 0 0
Mexico
State/province [128] 0 0
Nuevo LEON
Country [129] 0 0
Mexico
State/province [129] 0 0
Yucatán
Country [130] 0 0
Mexico
State/province [130] 0 0
Campeche
Country [131] 0 0
Mexico
State/province [131] 0 0
Chihuahua
Country [132] 0 0
Mexico
State/province [132] 0 0
Colima
Country [133] 0 0
Mexico
State/province [133] 0 0
Oaxaca
Country [134] 0 0
Netherlands
State/province [134] 0 0
Amsterdam
Country [135] 0 0
Netherlands
State/province [135] 0 0
Breda
Country [136] 0 0
Netherlands
State/province [136] 0 0
Deventer
Country [137] 0 0
Netherlands
State/province [137] 0 0
Utrecht
Country [138] 0 0
Poland
State/province [138] 0 0
Bydgoszcz
Country [139] 0 0
Poland
State/province [139] 0 0
Koszalin
Country [140] 0 0
Poland
State/province [140] 0 0
Krakow
Country [141] 0 0
Poland
State/province [141] 0 0
Lodz
Country [142] 0 0
Poland
State/province [142] 0 0
Opole
Country [143] 0 0
Poland
State/province [143] 0 0
Warszawa
Country [144] 0 0
Poland
State/province [144] 0 0
Slaskie
Country [145] 0 0
Portugal
State/province [145] 0 0
Lisboa
Country [146] 0 0
Portugal
State/province [146] 0 0
Porto
Country [147] 0 0
Puerto Rico
State/province [147] 0 0
Ponce
Country [148] 0 0
Romania
State/province [148] 0 0
Bucharest
Country [149] 0 0
Romania
State/province [149] 0 0
Bucuresti
Country [150] 0 0
Romania
State/province [150] 0 0
Craiova
Country [151] 0 0
Romania
State/province [151] 0 0
Floresti
Country [152] 0 0
Romania
State/province [152] 0 0
Suceava
Country [153] 0 0
Russian Federation
State/province [153] 0 0
Krasnodar
Country [154] 0 0
Russian Federation
State/province [154] 0 0
Moscow
Country [155] 0 0
Russian Federation
State/province [155] 0 0
Moskva
Country [156] 0 0
Russian Federation
State/province [156] 0 0
Ryazan
Country [157] 0 0
Russian Federation
State/province [157] 0 0
Saint Petersburg
Country [158] 0 0
Russian Federation
State/province [158] 0 0
Sankt-Peterburg
Country [159] 0 0
Russian Federation
State/province [159] 0 0
Sochi
Country [160] 0 0
Singapore
State/province [160] 0 0
Singapore
Country [161] 0 0
Spain
State/province [161] 0 0
Alicante
Country [162] 0 0
Spain
State/province [162] 0 0
Barcelona
Country [163] 0 0
Spain
State/province [163] 0 0
Madrid
Country [164] 0 0
Spain
State/province [164] 0 0
Malaga
Country [165] 0 0
Spain
State/province [165] 0 0
Pamplona
Country [166] 0 0
Spain
State/province [166] 0 0
Santiago de Compostela
Country [167] 0 0
Spain
State/province [167] 0 0
Sevilla
Country [168] 0 0
Spain
State/province [168] 0 0
Valencia
Country [169] 0 0
Switzerland
State/province [169] 0 0
Basel
Country [170] 0 0
Switzerland
State/province [170] 0 0
Lausanne
Country [171] 0 0
Switzerland
State/province [171] 0 0
Thun
Country [172] 0 0
Taiwan
State/province [172] 0 0
Kaohsiung
Country [173] 0 0
Taiwan
State/province [173] 0 0
Tainan City
Country [174] 0 0
Taiwan
State/province [174] 0 0
Tainan
Country [175] 0 0
Taiwan
State/province [175] 0 0
Taipei
Country [176] 0 0
Turkey
State/province [176] 0 0
Adana
Country [177] 0 0
Turkey
State/province [177] 0 0
Ankara
Country [178] 0 0
Turkey
State/province [178] 0 0
Antalya
Country [179] 0 0
Turkey
State/province [179] 0 0
Istanbul
Country [180] 0 0
United Kingdom
State/province [180] 0 0
Manchester
Country [181] 0 0
United Kingdom
State/province [181] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Bristol-Myers Squibb
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT04109066
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Bristol-Myers Squibb
Address 0 0
Bristol-Myers Squibb
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



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT04109066