A Study of the Efficacy and Safety of Atezolizumab Plus Chemotherapy for Patients With Early Relapsing Recurrent Triple-Negative Breast Cancer

NCT ID: NCT03371017

Last Updated: 2025-11-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 595 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-01-11
• Study Completion Date: 2024-10-23

Brief Summary

This study will evaluate the efficacy and safety of atezolizumab plus chemotherapy compared with placebo plus chemotherapy in patients with inoperable recurrent triple-negative breast cancer (TNBC).

Conditions

Triple Negative Breast Neoplasms

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Atezolizumab

Participants will receive Atezolizumab on day 1 of each 3-week treatment cycle

Group Type: EXPERIMENTAL

Atezolizumab

Intervention Type: DRUG

Atezolizumab will be administered, 1200 mg by IV infusion with :

gemcitabine 1000 mg/m2, followed by carboplatin target area under the curve (AUC) 2 mg/ml/min, both administered by IV infusion on Days 1 and 8 of each 3-week treatment cycle or with capecitabine 1000 mg/m2, twice daily orally on Days 1 to 14, followed by a 7-day rest period in each 3-week treatment cycle

Gemcitabine

Intervention Type: DRUG

Gemcitabine 1000 mg/m2, followed by carboplatin target area under the curve (AUC) 2 mg/ml/min, both administered by IV infusion on Days 1 and 8 of each 3-week treatment cycle

Capecitabine

Intervention Type: DRUG

Capecitabine 1000 mg/m2, twice daily orally on Days 1 to 14, followed by a 7-day rest period in each 3-week treatment cycle

Carboplatin

Intervention Type: DRUG

Carboplatin target area under the curve (AUC) 2 mg/ml/min, both administered by IV infusion on Days 1 and 8 of each 3-week treatment cycle

Placebo

Participants will receive Placebo on day 1 of each 3-week treatment cycle

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo will be administered, 1200 mg by IV infusion with :

gemcitabine 1000 mg/m2, followed by carboplatin target area under the curve (AUC) 2 mg/ml/min, both administered by IV infusion on Days 1 and 8 of each 3-week treatment cycle or with capecitabine 1000 mg/m2, twice daily orally on Days 1 to 14, followed by a 7-day rest period in each 3-week treatment cycle

Gemcitabine

Intervention Type: DRUG

Gemcitabine 1000 mg/m2, followed by carboplatin target area under the curve (AUC) 2 mg/ml/min, both administered by IV infusion on Days 1 and 8 of each 3-week treatment cycle

Capecitabine

Intervention Type: DRUG

Capecitabine 1000 mg/m2, twice daily orally on Days 1 to 14, followed by a 7-day rest period in each 3-week treatment cycle

Carboplatin

Intervention Type: DRUG

Carboplatin target area under the curve (AUC) 2 mg/ml/min, both administered by IV infusion on Days 1 and 8 of each 3-week treatment cycle

Interventions

Atezolizumab

Atezolizumab will be administered, 1200 mg by IV infusion with :

gemcitabine 1000 mg/m2, followed by carboplatin target area under the curve (AUC) 2 mg/ml/min, both administered by IV infusion on Days 1 and 8 of each 3-week treatment cycle or with capecitabine 1000 mg/m2, twice daily orally on Days 1 to 14, followed by a 7-day rest period in each 3-week treatment cycle

Intervention Type: DRUG

Placebo

Placebo will be administered, 1200 mg by IV infusion with :

gemcitabine 1000 mg/m2, followed by carboplatin target area under the curve (AUC) 2 mg/ml/min, both administered by IV infusion on Days 1 and 8 of each 3-week treatment cycle or with capecitabine 1000 mg/m2, twice daily orally on Days 1 to 14, followed by a 7-day rest period in each 3-week treatment cycle

Intervention Type: DRUG

Gemcitabine

Gemcitabine 1000 mg/m2, followed by carboplatin target area under the curve (AUC) 2 mg/ml/min, both administered by IV infusion on Days 1 and 8 of each 3-week treatment cycle

Intervention Type: DRUG

Capecitabine

Capecitabine 1000 mg/m2, twice daily orally on Days 1 to 14, followed by a 7-day rest period in each 3-week treatment cycle

Intervention Type: DRUG

Carboplatin

Carboplatin target area under the curve (AUC) 2 mg/ml/min, both administered by IV infusion on Days 1 and 8 of each 3-week treatment cycle

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Histologically confirmed triple negative breast cancer (TNBC) that is either locally recurrent, inoperable and cannot be treated with curative intent or is metastatic
• Documented disease progression occurring within 12 months from the last treatment with curative intent
• Prior treatment (of early breast cancer) with an anthracycline and taxane
• Have not received prior chemotherapy or targeted systemic therapy for their locally advanced inoperable or metastatic recurrence. Prior radiation therapy for recurrent disease is permitted
• Measurable or non-measurable disease, as defined by RECIST 1.1
• Availability of a representative formalin-fixed, paraffin-embedded (FFPE) tumour block (preferred) or at least 17 unstained slides obtained from relapsed metastatic or locally advanced diseases may be submitted, if clinically feasible, with an associated pathology report, if available. If a fresh tumour sample is not clinically feasible, either the diagnosis sample, the primary surgical resection sample, or the most recent FFPE tumour biopsy sample should be used.
• Eastern Cooperative Oncology Group performance status 0-1
• Life expectancy ≥ 12 weeks
• Adequate haematologic and end-organ function
• Negative human immunodeficiency virus (HIV) test ---Negative hepatitis B surface antigen (HBsAg) test at screening
• Negative total hepatitis B core antibody (HBcAb) test at screening, or positive HBcAb test followed by a negative hepatitis B virus (HBV) DNA test at screening
• The HBV DNA test will be performed only for patients who have a negative HBsAg and a positive HBcAb test.
• Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening.
• Women of childbearing potential must agree to remain abstinent (refrain from heterosexual intercourse) or use a contraceptive method with a failure rate of ≤1% per year during the treatment period and for at least 5 months after the last dose of atezolizumab or 6 months after the last dose of capecitabine, whichever is later. In addition, women must refrain from donating eggs during the same time period.
• Men must agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agree to refrain from donating sperm

-PD-L1-positive tumour status (assessed centrally prior to randomisation), defined as PD-L1 expression on tumour-infiltrating immune cells (IC) of 1% or greater.

Exclusion Criteria

• Spinal cord compression not definitively treated with surgery and/or radiation, or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for > 2 weeks prior to randomisation
• Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases.
• Symptomatic or rapid visceral progression
• No prior treatment with an anthracycline and taxane
• History of leptomeningeal disease
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently) (patients with indwelling catheters such as PleurX® are allowed)
• Uncontrolled tumour-related pain
• Uncontrolled or symptomatic hypercalcemia
• Malignancies other than TNBC within 5 years prior to randomisation)
• Significant cardiovascular disease, within 3 months prior to randomisation, unstable arrhythmias, or unstable angina
• Presence of an abnormal ECG
• Severe infection requiring oral or IV antibiotics within 4 weeks prior to randomisation, including but not limited to hospitalization for complications of infection, bacteraemia, or severe pneumonia.
• Current treatment with anti-viral therapy for HBV.
• Major surgical procedure within 4 weeks prior to randomisation or anticipation of the need for a major surgical procedure during the course of the study other than for diagnosis
• Treatment with investigational therapy within 28 days prior to randomisation
• Pregnant or lactating, or intending to become pregnant during or within 5 months after the last dose of atezolizumab, or within 6 months after the last dose of capecitabine, whichever is later.

• History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanised antibodies or fusion proteins
• Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or to any component of the atezolizumab formulation
• History of autoimmune disease
• Prior allogeneic stem cell or solid organ transplantation
• History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e. bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest computerised tomography (CT) scan History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
• Active tuberculosis
• Receipt of a live, attenuated vaccine within 4 weeks prior to randomisation or anticipation that a live, attenuated vaccine will be required during atezolizumab/placebo treatment or within 5 months after the last dose of atezolizumab/placebo
• Prior treatment with CD137 agonists, anti-PD-1, or anti-PD-L1 therapeutic antibody or pathway targeting agents
• Treatment with systemic immunostimulatory agents (including but not limited to interferons or interleukin [IL]-2) within 4 weeks or five half-lives of the drug (whichever is longer) prior to randomisation
• Treatment with systemic corticosteroids or other systemic immunosuppressive medications within 2 weeks prior to start of study treatment, or anticipated requirement for systemic immunosuppressive medications during the trial

• Inability to swallow pills
• Malabsorption syndrome, disease significantly affecting gastrointestinal function, resection of the stomach or small bowel, or ulcerative colitis
• Known dihydropyrimidine dehydrogenase (DPD) deficiency or history of severe and unexpected reactions to fluoropyrimidine therapy in patients selected to receive capecitabine

-Hypersensitivity to platinum containing compounds or any component of carboplatin or gemcitabine drug formulations in patients selected to receive carboplatin and Gemcitabine

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

Florida Cancer Specialists - Fort Myers (Broadway)

Fort Myers, Florida, United States

Florida Cancer Specialists & Research Institute

St. Petersburg, Florida, United States

The Valley Hospital

Paramus, New Jersey, United States

Magee-Woman's Hospital

Pittsburgh, Pennsylvania, United States

SCRI Oncology Partners

Nashville, Tennessee, United States

Inova Schar Cancer Institute

Fairfax, Virginia, United States

Hospital Provincial del Centenario

Rosario, , Argentina

Instituto de Oncología de Rosario

Rosario, , Argentina

Clinical center University of Sarajevo

Sarajevo, , Bosnia and Herzegovina

Oncocentro Serviços Medicos E Hospitalares Ltda

Fortaleza, Ceará, Brazil

Hospital Araujo Jorge

Goiânia, Goiás, Brazil

Hospital do Cancer de Pernambuco - HCP

Recife, Pernambuco, Brazil

Hospital Sao Vicente de Paulo

Passo Fundo, Rio Grande do Sul, Brazil

Hospital Nossa Senhora da Conceicao

Porto Alegre, Rio Grande do Sul, Brazil

Centro de Oncologia de Santa Catarina LTDA

Chapecó, Santa Catarina, Brazil

Instituto de Pesquisa Grupo NotreDame Intermedica

São Paulo, São Paulo, Brazil

Hospital Perola Byington

São Paulo, São Paulo, Brazil

Núcleo de Pesquisa São Camilo

São Paulo, São Paulo, Brazil

Bradford Hill Centro de Investigaciones Clinicas

Recoleta, , Chile

Clinica Vespucio

Santiago, , Chile

the First Affiliated Hospital of Bengbu Medical College

Anhui, , China

Cancer Hospital , Chinese Academy of Medical

Beijing, , China

Peking University People's Hospital

Beijing, , China

Beijing Cancer Hospital

Beijing, , China

Jilin Cancer Hospital

Changchun, , China

The First Affiliated Hospital, Chongqing Medical University

Chongqing, , China

Fujian Medical University Union Hospital

Fujian, , China

Sun Yat-sen Memorial Hospital

Guangzhou, , China

Sir Run Run Shaw Hospital Zhejiang University

Hangzhou, , China

Zhejiang Cancer Hospital

Hangzhou, , China

Harbin Medical University Cancer Hospital

Harbin, , China

The First Affiliated Hospital Of Jinzhou Medical University

Jinzhou, , China

Jiangsu Province Hospital

Nanjing, , China

The Affiliated Hospital of Medical College Qingdao University

Qingdao, , China

Fudan University Shanghai Cancer Center

Shanghai, , China

Shanxi Province Cancer Hospital

Taiyuan, , China

Tianjin Cancer Hospital

Tianjin, , China

The First Affiliated Hospital of The Fourth Military Medical University (Xijing Hospital)

Xi'an, , China

Hospital Hermanos Ameijeiras

La Habana, , Cuba

Instituto Nacional de Oncología y Radiología (INOR)

La Habana, , Cuba

Helsinki University Central Hospital

Helsinki, , Finland

Tampere University Hospital

Tampere, , Finland

Centre Georges-François Lecler

Dijon, , France

Centre Leon Berard

Lyon, , France

Institut Paoli-Calmettes

Marseille, , France

Centre Régional de Lutte Contre Le Cancer Val D'aurelle Paul Lamarque

Montpellier, , France

Centre Eugene Marquis

Rennes, , France

Centre Alexis Vautrin

Vandœuvre-lès-Nancy, , France

IGR

Villejuif, , France

Universitätsklinikum "Carl Gustav Carus"

Dresden, , Germany

Klinikum Essen-Mitte Ev. Huyssens-Stiftung / Knappschafts GmbH

Essen, , Germany

Varisano Klinikum Frankfurt Höchst GmbH

Frankfurt, , Germany

Universitätsklinikum Halle (Saale)

Halle, , Germany

Medizinische Hochschule Hannover, Klinik für Frauenheilkunde und Geburtshilfe

Hanover, , Germany

Nationales Centrum für Tumorerkrankungen (NCT)

Heidelberg, , Germany

Medizinisches Zentrum für Hämatologie und Onkologie

München, , Germany

Szent Margit Hospital

Budapest, , Hungary

Orszagos Onkologiai Intezet

Budapest, , Hungary

Budapesti Uzsoki Utcai Kórház

Budapest, , Hungary

Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi Oktato Korhaz

Miskolc, , Hungary

Pécsi Tudományegyetem

Pécs, , Hungary

Ospedale Antonio Perrino

Brindisi, Apulia, Italy

Istituto Nazionale per lo Studio e la Cura dei Tumori Fondazione G. Pascale

Napoli, Campania, Italy

Azienda Ospedaliero Universitaria San Martino

Genoa, Liguria, Italy

Ospedale San Raffaele S.r.l.

Milan, Lombardy, Italy

Irccs Istituto Europeo Di Oncologia (IEO)

Milan, Lombardy, Italy

Ospedale San Gerardo

Monza, Lombardy, Italy

Fondazione Del Piemonte Per L'oncologia Ircc Di Candiolo

Candiolo, Piedmont, Italy

Azienda Ospedaliero-Universitaria Careggi

Florence, Tuscany, Italy

IRCCS Istituto Oncologico Veneto (IOV)

Padua, Veneto, Italy

Kazakh Scientific Research Institution Of Oncology and Radiology

Almaty, , Kazakhstan

Centro Medico Dalinde

Mexico City, Mexico CITY (federal District), Mexico

Instituto Nacional de Cancerologia

Distrito Federal, , Mexico

CENEIT Oncologicos

Mexico City, , Mexico

Clinical Center of Montenegro

Podgorica, , Montenegro

Centre Hospitalier Universitaire Hassan II

Fes, , Morocco

Centre Hospitalier Universitaire Mohamed VI

Marrakesh, , Morocco

Clinique specialise Menara

Marrakesh, , Morocco

The Panama Clinic

Panama City, , Panama

Instituto Nacional de Enfermedades Neoplasicas

Lima, , Peru

?wi?tokrzyskie Centrum Onkologii

Kielce, , Poland

Narodowy Inst.Onkologii im.Sklodowskiej-Curie Panstw.Inst.Bad

Warsaw, , Poland

Hospital de Santa Maria

Lisbon, , Portugal

Centro Hospitalar do Porto ? Hospital de Santo António

Porto, , Portugal

Moscow City Oncology Hospital #62

Moscovskaya Oblast, Moscow Oblast, Russia

Moscow Clinical Scientific Center

Moscow, Moscow Oblast, Russia

FSBI "National Medical Research Center of Oncology N.N. Blokhin?

Moscow, Moscow Oblast, Russia

Private Healthcare Institution Clinical Hospital RZhD Medicine

Saint Petersburg, Sankt-Peterburg, Russia

City Clinical Oncology Dispensary, SPb SBIH CCOD

Saint Petersburg, Sankt-Peterburg, Russia

FBI "Scientific Research Institute of Oncology n. a. N. N. Petrov"

Saint Petersburg, Sankt-Peterburg, Russia

Institute of Oncology and Radiology of Serbia

Belgrade, , Serbia

University Hospital Medical Center Bezanijska kosa

Belgrade, , Serbia

Oncology Institute of Vojvodina

Kamenitz, , Serbia

Clinical Centre Nis, Clinic for Oncology

Niš, , Serbia

National Cancer Centre

Singapore, , Singapore

Wits Clinical Research

Johannesburg, , South Africa

Medical Oncology Centre of Rosebank

Johannesburg, , South Africa

Private Oncology Centre

Pretoria, , South Africa

Seoul National University Bundang Hospital

Gyeonggi-do, , South Korea

Seoul National University Hospital

Seoul, , South Korea

Severance Hospital, Yonsei University Health System

Seoul, , South Korea

Asan Medical Center

Seoul, , South Korea

Samsung Medical Center

Seoul, , South Korea

Hospital de Cruces

Bilbao, Vizcaya, Spain

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Hospital General Universitario Gregorio Marañon

Madrid, , Spain

Hospital Ramon y Cajal

Madrid, , Spain

Hospital Clinico Universitario Virgen de la Victoria

Málaga, , Spain

Hospital Clínico Universitario de Valencia

Valencia, , Spain

Ankara Oncology Hospital

Ankara, , Turkey (Türkiye)

Ege University Medical Faculty

Bornova, ?zm?r, , Turkey (Türkiye)

Trakya Universitesi Tip Fakultesi, Medikal Onkoloji Bilim Dali, Balkan Yerleskesi

Edirne, , Turkey (Türkiye)

Medipol University Medical Faculty

Istanbul, , Turkey (Türkiye)

Marmara University Pendik Training and Research Hospital

Istanbul, , Turkey (Türkiye)

Necmettin Erbakan University Meram Medical Faculty

Konya, , Turkey (Türkiye)

Velindre Cancer Centre

Cardiff, , United Kingdom

University Hospital Coventry

Coventry, , United Kingdom

Western General Hospital

Edinburgh, , United Kingdom

Royal Lancaster Infirmary, Morecambe Bay Hospitals Nhs Trust

Lancaster, , United Kingdom

Barts

London, , United Kingdom

Guys and St Thomas NHS Foundation Trust, Guys Hospital

London, , United Kingdom

Christie Hospital NHS Trust

Manchester, , United Kingdom

Mount Vernon Cancer Centre

Northwood, , United Kingdom

Royal Stoke University Hospital

Stoke-on-Trent, , United Kingdom

Countries

Algeria; Egypt; United States; Argentina; Bosnia and Herzegovina; Brazil; Chile; China; Cuba; Finland; France; Germany; Hungary; Italy; Kazakhstan; Mexico; Montenegro; Morocco; Panama; Peru; Poland; Portugal; Russia; Serbia; Singapore; South Africa; South Korea; Spain; Turkey (Türkiye); United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2016-005119-42

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MO39193

Identifier Type: -

Identifier Source: org_study_id