A Study of Atezolizumab and Paclitaxel Versus Placebo and Paclitaxel in Participants With Previously Untreated Locally Advanced or Metastatic Triple Negative Breast Cancer (TNBC)

NCT ID: NCT03125902

Last Updated: 2024-03-26

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

653 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-08-25

Study Completion Date

2023-01-17

Brief Summary

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This Phase 3, multicenter, randomized, double-blind, placebo controlled study is designed to evaluate the efficacy and safety of atezolizumab (MPDL3280A, an anti-programmed death-ligand 1 \[PD-L1\] antibody) administered in combination with paclitaxel compared with placebo in combination with paclitaxel in participants with previously untreated, inoperable locally advanced or metastatic, centrally confirmed TNBC. Participants will be randomized in a 2:1 ratio to receive atezolizumab or placebo plus paclitaxel until disease progression or unacceptable toxicity or end of study, whichever occurs first (maximum up to approximately 40 months). In addition, the Sponsor may decide to terminate the study at any time.

Detailed Description

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Conditions

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Triple-Negative Breast Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators
The Sponsor and its agents; the study site personnel, including the investigator; and the participant will be blinded to treatment assignment.

Study Groups

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Placebo and Paclitaxel

Participants will receive placebo matching to atezolizumab via IV infusion on Days 1 and 15 (± 3 days) of every 28-day cycle along with paclitaxel administered at a dose of 90 mg/m\^2 via IV infusion on Days 1, 8, and 15 of every 28-day cycle until disease progression or unacceptable toxicity.

Group Type PLACEBO_COMPARATOR

Atezolizumab (MPDL3280A), an engineered anti-PDL1 antibody

Intervention Type DRUG

Atezolizumab will be administered at a dose of 840 mg via IV infusion on Days 1 and 15 (± 3 days) of every 28-day cycle.

Paclitaxel

Intervention Type DRUG

Paclitaxel will be administered at a dose of 90 mg/m\^2 via IV infusion on Days 1, 8, and 15 of every 28-day cycle.

Atezolizumab and Paclitaxel

Participants will receive atezolizumab at a dose of 840 milligrams (mg) via intravenous (IV) infusion on Days 1 and 15 (± 3 days) of every 28-day cycle along with paclitaxel administered at a dose of 90 mg per square meter (mg/m\^2) via IV infusion on Days 1, 8, and 15 of every 28-day cycle until disease progression or unacceptable toxicity.

Group Type EXPERIMENTAL

Atezolizumab Placebo

Intervention Type DRUG

Placebo matching to atezolizumab will be administered via IV infusion on Days 1 and 15 (± 3 days) of every 28-day cycle.

Paclitaxel

Intervention Type DRUG

Paclitaxel will be administered at a dose of 90 mg/m\^2 via IV infusion on Days 1, 8, and 15 of every 28-day cycle.

Interventions

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Atezolizumab (MPDL3280A), an engineered anti-PDL1 antibody

Atezolizumab will be administered at a dose of 840 mg via IV infusion on Days 1 and 15 (± 3 days) of every 28-day cycle.

Intervention Type DRUG

Atezolizumab Placebo

Placebo matching to atezolizumab will be administered via IV infusion on Days 1 and 15 (± 3 days) of every 28-day cycle.

Intervention Type DRUG

Paclitaxel

Paclitaxel will be administered at a dose of 90 mg/m\^2 via IV infusion on Days 1, 8, and 15 of every 28-day cycle.

Intervention Type DRUG

Other Intervention Names

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MPDL3280A, TECENTRIQ

Eligibility Criteria

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Inclusion Criteria

* Participants with locally advanced or metastatic, histologically documented TNBC (absence of human epidermal growth factor receptor 2 \[HER2\], estrogen receptor \[ER\], and progesterone receptor \[PR\] expression), not amenable to surgical therapy
* Participants eligible for taxane monotherapy
* No prior chemotherapy or targeted systemic therapy (including endocrine therapy) for inoperable locally advanced or metastatic TNBC
* Availability of formalin-fixed paraffin-embedded (FFPE) tumor block (preferred) or at least 17 unstained slides, collected ≤3 months prior to randomization, with an associated pathology report, if available. If a tumour sample taken within 3 months before randomisation is not available and a tumour biopsy is not clinically feasible, the primary surgical resection sample or the most recent FFPE tumour biopsy sample may be used. Of these additional options, the most recent sample should be used.
* Eastern Cooperative Oncology Group performance status of 0 or 1
* Life expectancy at least 12 weeks
* Measurable disease, as defined by RECIST v1.1
* Adequate hematologic and end-organ function
* Negative human immunodeficiency virus (HIV) test at screening.
* 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 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. The HCV RNA test will be performed only for patients who have a positive HCV antibody test.
* Women of child bearing potential must have a negative serum pregnancy test result within 7 days prior to initiation of study drug
* For men and women of child bearing potential: agreement to remain abstinent or use protocol defined contraceptive measures during the treatment period and for at least 5 months after the last dose of atezolizumab/placebo, or for at least 6 months after the last dose of paclitaxel

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 at least 2 weeks prior to randomization
* Known central nervous system (CNS) disease, except for treated asymptomatic CNS metastases
* Leptomeningeal disease
* Uncontrolled pleural effusion, pericardial effusion, or ascites
* Uncontrolled tumor-related pain, or uncontrolled hypercalcemia or clinically significant (symptomatic) hypercalcemia
* Malignancies other than TNBC within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or Stage I uterine cancer)
* Pregnant or breast-feeding women, or intending to become pregnant during the study
* Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results, including significant liver disease, cardiovascular disease, and presence of an abnormal electrocardiogram (ECG)
* Serious infection requiring antibiotics within 2 weeks prior to randomization, including but not limited to infections requiring hospitalization or IV antibiotics, such as bacteremia, or severe pneumonia
* Major surgical procedure within 4 weeks prior to randomization or anticipation of the need for a major surgical procedure during the study other than for diagnosis
* Treatment with investigational therapy within 30 days prior to initiation of study treatment
* History of hypersensitivity reactions to study drug or any component of the study drug formulation
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hoffmann-La Roche

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

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Stanford Cancer Center

Stanford, California, United States

Site Status

Florida Cancer Specialists; Department of Oncology

Fort Myers, Florida, United States

Site Status

Florida Cancer Specialist, North Region

St. Petersburg, Florida, United States

Site Status

Northwest Georgia Oncology Centers PC - Marietta

Marietta, Georgia, United States

Site Status

HCA Midwest Health

Kansas City, Missouri, United States

Site Status

The Valley Hospital

Paramus, New Jersey, United States

Site Status

Magee-Woman's Hospital

Pittsburgh, Pennsylvania, United States

Site Status

Tennessee Oncology; Sarah Cannon Research Institute

Nashville, Tennessee, United States

Site Status

Centro Oncologico Riojano Integral (CORI)

La Rioja, , Argentina

Site Status

Centro de Pesquisas Clinicas em Oncologia - CPCO

Cachoeiro de Itapemirim, Espírito Santo, Brazil

Site Status

Santa Casa de Misericordia de Salvador

Salvador, Estado de Bahia, Brazil

Site Status

Hospital Araujo Jorge; Departamento de Ginecologia E Mama

Goiânia, Goiás, Brazil

Site Status

Hospital Nossa Senhora da Conceicao

Porto Alegre, Rio Grande do Sul, Brazil

Site Status

Hospital Sao Lucas - PUCRS

Porto Alegre, Rio Grande do Sul, Brazil

Site Status

Hospital Perola Byington

São Paulo, São Paulo, Brazil

Site Status

Tom Baker Cancer Centre-Calgary

Calgary, Alberta, Canada

Site Status

Cross Cancer Institute

Edmonton, Alberta, Canada

Site Status

Kingston General Hospital

Kingston, Ontario, Canada

Site Status

Grand River Hospital

Kitchener, Ontario, Canada

Site Status

London Regional Cancer Centre

London, Ontario, Canada

Site Status

Sunnybrook Odette Cancer Centre

Toronto, Ontario, Canada

Site Status

McGill University; Glen Site; Oncology

Montreal, Quebec, Canada

Site Status

Hopital du Saint Sacrement

Québec, Quebec, Canada

Site Status

Centre Hospitalier Universitaire de Sherbrooke - Hopital Fleurimont

Sherbrooke, Quebec, Canada

Site Status

Cancer Hospital Chinese Academy of Medical Sciences.

Beijing, , China

Site Status

Beijing Union Hospital

Beijing, , China

Site Status

West China Hospital, Sichuan University; Department of Breast

Chengdu, , China

Site Status

Sun Yat-sen Memorial Hospital

Guangzhou, , China

Site Status

Harbin Medical University Cancer Hospital

Harbin, , China

Site Status

Shandong Cancer Hospital

Jinan, , China

Site Status

Jiangsu Province Hospital (the First Affiliated Hospital With Nanjing Medical University)

Nanjing, , China

Site Status

Jiangsu Cancer Hospital

Nanjing, , China

Site Status

Shanghai Jiao Tong University School of Medicine (SJTUSM) - Ruijin Hospital (GuangCi Hospital)

Shanghai, , China

Site Status

Fudan University Shanghai Cancer Center

Shanghai, , China

Site Status

Liaoning cancer Hospital & Institute

Shenyang, , China

Site Status

Hebei Medical University Fourth Hospital;(Tumor Hospital of Hebei Province)

Shijiazhuang, , China

Site Status

Tianjin Medical University Cancer Institute & Hospital

Tianjin, , China

Site Status

The Second Affiliated Hospital of Xi'an Jiao Tong University

Xi'an, , China

Site Status

First Affiliated Hospital of Medical College of Xi'an Jiaotong University

Xi'an, , China

Site Status

Zhejiang Cancer Hospital

Zhejiang, , China

Site Status

Henan Cancer Hospital

Zhengzhou, , China

Site Status

Clinical Hospital Centre Zagreb

Zagreb, , Croatia

Site Status

Fakultni Nemocnice Hradec Kralove; Dept of Radiotherapy & Oncology

Hradec Králové, , Czechia

Site Status

Fakultni nemocnice Olomouc; Onkologicka klinika

Olomouc, , Czechia

Site Status

Fakultni nemocnice Ostrava; Klinika onkologicka FNO a LF OU

Ostrava-Poruba, , Czechia

Site Status

Fakultni Poliklinika Vseobecne Fakultni Niemocnice; Onkologicka Klinika

Prague, , Czechia

Site Status

Clinique Sainte Catherine; Hopital De Semaine

Avignon, , France

Site Status

HOPITAL JEAN MINJOZ; Oncologie

Besançon, , France

Site Status

Polyclinique Bordeaux Nord Aquitaine

Bordeaux, , France

Site Status

Hopital Morvan

Brest, , France

Site Status

CHD Les Oudairies

La Roche-sur-Yon, , France

Site Status

Centre Oscar Lambret; Senologie

Lille, , France

Site Status

Centre Leon Berard; Departement Oncologie Medicale

Lyon, , France

Site Status

Centre D'Oncologie de Gentilly; Oncology

Nancy, , France

Site Status

Hopital Caremeau; Hematologie Oncologie

Nîmes, , France

Site Status

Hopital Tenon

Paris, , France

Site Status

Institut Curie; Oncologie Medicale

Paris, , France

Site Status

Hopital Saint Louis, Service D Oncologie Medicale

Paris, , France

Site Status

Ch Pitie Salpetriere; Oncologie Medicale

Paris, , France

Site Status

Centre Eugene Marquis; Service d'oncologie

Rennes, , France

Site Status

Centre Paul Strauss; Oncologie Medicale

Strasbourg, , France

Site Status

Institut Claudius Regaud; Departement Oncologie Medicale

Toulouse, , France

Site Status

Institut Gustave Roussy; Sitep

Villejuif, , France

Site Status

Ambulantes Tumorzentrum Spandau; Dres. Benno Mohr und Uwe Peters

Berlin, , Germany

Site Status

Onkologische Schwerpunktpraxis Bielefeld

Bielefeld, , Germany

Site Status

St. Elisabeth Krankenhaus Köln GmbH; Gynäkologie und Geburtshilfe

Cologne, , Germany

Site Status

Klinikum Essen-Mitte Ev. Huyssens-Stiftung / Knappschafts GmbH; Klinik für Senologie / Brustzentrum

Essen, , Germany

Site Status

HOPA im Struensee-Haus, Dres. Erik Engel, Wiebke Hollburg

Hamburg, , Germany

Site Status

Nationales Centrum für Tumorerkrankungen (NCT) ; Gyn. Onk. Frauenklinik; Uniklinikum Heidelberg

Heidelberg, , Germany

Site Status

Universitätsmedizin Mainz; Klinik u. Poliklinik f. Geburtshilfe u. Frauenheilkunde

Mainz, , Germany

Site Status

OnkoNet Marburg GmbH

Marburg, , Germany

Site Status

Klinik & Poliklinik für Frauenheilkunde und Geburtshilfe, Campus Innenstadt

München, , Germany

Site Status

Gemeinschaftspraxis für Hämatologie und Onkologie

Münster, , Germany

Site Status

Klinikum Ernst von Bergmann; Frauenklinik

Potsdam, , Germany

Site Status

Dres. Helmut Forstbauer, Carsten Ziske und Kollegen; Onkologische Schwerpunktpraxis

Troisdorf, , Germany

Site Status

Universitätsklinik Tübingen; Frauenklinik

Tübingen, , Germany

Site Status

Anticancer Hospital Ag. Savas ; 2Nd Dept. of Oncology - Internal Medicine

Athens, , Greece

Site Status

ARETAIEION UNIVERSITY HOSPITAL; oncology unit

Athens, , Greece

Site Status

Agioi Anargyroi Cancer Hospital; 2Nd Oncology Dept.

Kifissia, , Greece

Site Status

Papageorgiou General Hospital; Medical Oncology

Thessaloniki, , Greece

Site Status

Yashoda Hospital

Hyderabad, Andhra Pradesh, India

Site Status

Manipal Hospital; Department of Oncology

Bangalore, Karnataka, India

Site Status

Tata Memorial Hospital; Dept of Medical Oncology

Mumbai, Maharashtra, India

Site Status

Jehangir Hospital

Pune, Maharashtra, India

Site Status

Dr. B L Kapur Memorial Hospital; BLK Cancer Centre

New Delhi, National Capital Territory of Delhi, India

Site Status

Indraprastha Apollo Hospitals

New Delhi, National Capital Territory of Delhi, India

Site Status

Rajiv Gandhi Cancer Inst.&Research Center; Medical Oncology

New Delhi, National Capital Territory of Delhi, India

Site Status

Max Super Speciality Hospital; Medical Oncology

North WEST Delhi, National Capital Territory of Delhi, India

Site Status

Apollo Speciality Hospital

Chennai, Tamil Nadu, India

Site Status

Apollo Gleneagles Hospitals

Kolkata, West Bengal, India

Site Status

TATA Medical Centre; Medical Oncology

Kolkata, West Bengal, India

Site Status

MAX Balaji Hospital

Delhi, , India

Site Status

Hadassah Ein Karem Hospital; Oncology Dept

Jerusalem, , Israel

Site Status

Rabin MC; Davidof Center - Oncology Institute

Petah Tikva, , Israel

Site Status

Sheba Medical Center

Ramat Gan, , Israel

Site Status

Rambam Health Corporation; Oncology Institute

Rambam, , Israel

Site Status

Kaplan Medical Center

Rehovot, , Israel

Site Status

Tel Aviv Sourasky Medical Ctr; Oncology

Tel Aviv, , Israel

Site Status

Assaf Harofeh; Oncology

Ẕerifin, , Israel

Site Status

Fondazione Università G. D'Annunzio; Clinical Research Center (CRC); Centro Studi (CESI)

Chieti, Abruzzo, Italy

Site Status

Presidio Ospedaliero S. Giovanni Di Dio; U.O. Di Oncologia

Frattamaggiore, Campania, Italy

Site Status

Azienda Ospedaliera Universitaria Federico II

Napoli, Campania, Italy

Site Status

Istituto Nazionale Tumori Fondazione G. Pascale

Napoli, Campania, Italy

Site Status

Azienda Ospedaliero - Universitaria di Modena Policlinico

Modena, Emilia-Romagna, Italy

Site Status

Universita Campus Bio-Medico di Roma (UCBM)

Rome, Lazio, Italy

Site Status

IRCCS Istituto Regina Elena (IFO); Oncologia Medica B

Rome, Lazio, Italy

Site Status

Azienda Policlinico Umberto I

Rome, Lazio, Italy

Site Status

A.O. Universitaria S. Martino Di Genova

Genoa, Liguria, Italy

Site Status

Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII (Presidio Papa Giovanni XXIII)

Bergamo, Lombardy, Italy

Site Status

Asst Degli Spedali Civili Di Brescia

Brescia, Lombardy, Italy

Site Status

Hospital San Raffaele

Milan, Lombardy, Italy

Site Status

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, Lombardy, Italy

Site Status

IEO Istituto Europeo di Oncologia;Divisione Oncologia Medica

Milan, Lombardy, Italy

Site Status

IRCCS Istituto Clinico Humanitas; Oncologia

Rozzano (MI), Lombardy, Italy

Site Status

Fondazione Del Piemonte Per L'oncologia IRCC Di Candiolo

Candiolo, Piedmont, Italy

Site Status

Ospedale S. Vincenzo; Oncologia Medica

Taormina, Sicily, Italy

Site Status

Azienda Ospedaliero-Universitaria Careggi; SOD Radioterapia

Florence, Tuscany, Italy

Site Status

Ospedale Civile; Unita Operativa Di Oncologia Medica

Livorno, Tuscany, Italy

Site Status

IOV - Istituto Oncologico Veneto - IRCCS; Oncologia Medica II

Padua, Veneto, Italy

Site Status

Gunma Prefectural Cancer Center

Gunma, , Japan

Site Status

Hiroshima City Hiroshima Citizens Hospital

Hiroshima, , Japan

Site Status

Sagara Hospital

Kagoshima, , Japan

Site Status

Kanagawa Cancer Center

Kanagawa, , Japan

Site Status

Tokai University Hospital

Kanagawa, , Japan

Site Status

Niigata Cancer Center Hospital

Niigata, , Japan

Site Status

Naha-nishi Clinic

Okinawa, , Japan

Site Status

Osaka International Cancer Institute

Osaka, , Japan

Site Status

Saitama Cancer Center

Saitama, , Japan

Site Status

The Cancer Institute Hospital of JFCR

Tokyo, , Japan

Site Status

Centre Hospitalier Universitaire Mohamed VI; Oncologie-Hématologie

Marrakesh, , Morocco

Site Status

Institut National D'oncologie Sidi Mohammed Ben Abdellah; Anatomopathologie

Rabat, , Morocco

Site Status

Prof. Dr. I. Chiricuta Institute of Oncology

Cluj-Napoca, , Romania

Site Status

Centrul de Oncologie Sfantul Nectarie

Craiova, , Romania

Site Status

Russian Oncology Research Center n.a. N.N. Blokhin

Moscow, Moscow Oblast, Russia

Site Status

Petrov Research Inst. of Oncology

Saint Petersburg, , Russia

Site Status

King Fahad Specialist Hospital; Oncology

Dammam, , Saudi Arabia

Site Status

International Medical Center (IMC)

Jeddah, , Saudi Arabia

Site Status

King Fahad Medical City; Gastroentrology

Riyadh, , Saudi Arabia

Site Status

Narodny Onkologicky Ustav; Oddelenie klinickej onkologie A

Bratislava, , Slovakia

Site Status

POKO Poprad; Department of Oncology

Poprad, , Slovakia

Site Status

Wilgers Oncology Centre

Pretoria, , South Africa

Site Status

Private Oncology Centre

Pretoria, , South Africa

Site Status

Sandton Oncology Medical Group

Sandton, , South Africa

Site Status

Complejo Hospitalario Universitario A Coruña (CHUAC); Servicio de Oncologia

A Coruña, LA Coruña, Spain

Site Status

Hospital Clínic i Provincial; Servicio de Hematología y Oncología

Barcelona, , Spain

Site Status

Hospital Universitario de Fuenlabrada; Servicio de Oncologia

Madrid, , Spain

Site Status

Hospital Universitario Virgen Macarena; Servicio de Oncologia

Seville, , Spain

Site Status

Hospital Universitario Virgen del Rocio; Servicio de Oncologia

Seville, , Spain

Site Status

Adana Baskent University Medical Faculty; Oncology

Adana, , Turkey (Türkiye)

Site Status

Ankara Bilkent City Hospital

Ankara, , Turkey (Türkiye)

Site Status

Uludag University Medical Faculty; Internal Medicine

Bursa, , Turkey (Türkiye)

Site Status

Dicle Uni Medical Faculty; Internal Medicine

Diyarbakır, , Turkey (Türkiye)

Site Status

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

Edirne, , Turkey (Türkiye)

Site Status

Izmir Ataturk Training and Research Hospital

Izmir, , Turkey (Türkiye)

Site Status

Kocaeli University Faculty of Medicine; Medical oncology

İzmit, , Turkey (Türkiye)

Site Status

Goztepe Prof.Dr. Suleyman Yalcin City Hospital; Clinical Oncology

Kadiköy, , Turkey (Türkiye)

Site Status

Guys and St Thomas NHS Foundation Trust, Guys Hospital

London, , United Kingdom

Site Status

Christie Hospital

Manchester, , United Kingdom

Site Status

Mount Vernon Cancer Centre

Northwood, , United Kingdom

Site Status

K hospital

Hanoi, , Vietnam

Site Status

Hochiminh city oncology hospital

Hochiminh City, , Vietnam

Site Status

Countries

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United States Argentina Brazil Canada China Croatia Czechia France Germany Greece India Israel Italy Japan Morocco Romania Russia Saudi Arabia Slovakia South Africa Spain Turkey (Türkiye) United Kingdom Vietnam

References

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Miles D, Gligorov J, Andre F, Cameron D, Schneeweiss A, Barrios C, Xu B, Wardley A, Kaen D, Andrade L, Semiglazov V, Reinisch M, Patel S, Patre M, Morales L, Patel SL, Kaul M, Barata T, O'Shaughnessy J; IMpassion131 investigators. Primary results from IMpassion131, a double-blind, placebo-controlled, randomised phase III trial of first-line paclitaxel with or without atezolizumab for unresectable locally advanced/metastatic triple-negative breast cancer. Ann Oncol. 2021 Aug;32(8):994-1004. doi: 10.1016/j.annonc.2021.05.801. Epub 2021 Jul 1.

Reference Type DERIVED
PMID: 34219000 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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Other Identifiers

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2016-004024-29

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MO39196

Identifier Type: -

Identifier Source: org_study_id

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