A Study To Evaluate the Efficacy and Safety Of Atezolizumab or Placebo in Combination With Neoadjuvant Doxorubicin + Cyclophosphamide Followed By Paclitaxel + Trastuzumab + Pertuzumab In Early Her2-Positive Breast Cancer
NCT ID: NCT03726879
Last Updated: 2024-11-05
Study Results
Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
PHASE3
454 participants
INTERVENTIONAL
2019-01-11
2023-08-24
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Safety and Pharmacokinetics of Atezolizumab Combination Treatments in Participants With HER2-Positive and HER2-Negative Breast Cancer
NCT02605915
Combination Chemotherapy With or Without Trastuzumab in Treating Women With Breast Cancer
NCT00021255
Clinical Trial of Atezolizumab With Paclitaxel, Trastuzumab, and Pertuzumab in Patients With Metastatic HER-2 Positive Breast Cancer
NCT03125928
Neoadjuvant Treatment of HER2 Positive Early High-risk and Locally Advanced Breast Cancer
NCT03595592
A Study of Pertuzumab in Combination With Herceptin and Chemotherapy in Participants With HER2-Positive Breast Cancer
NCT00976989
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
TREATMENT
DOUBLE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Atezolizumab +ddAC-PacHP
Participants will receive atezolizumab (atezo) 840 mg IV Q2W for 4 cycles during neoadjuvant phase with ddAC (doxorubicin 60 mg/m2 \& cyclophosphamide 600 mg/m2 IV), followed by atezo 1200 mg IV Q3W for 4 cycles with paclitaxel 80 mg/m2 IV weekly for 12 continuous weeks, trastuzumab 6 mg/kg IV (with initial 8mg/kg IV loading dose) Q3W for 4 cycles, \& pertuzumab 420 mg IV (with initial 840-mg IV loading dose) Q3W for 4 cycles. During adjuvant phase, participants will continue to receive following study treatments Q3W to complete up to 1 year HER2-target therapy inclusive of therapy given both in neoadjuvant and adjuvant setting: atezo 1200 mg IV Q3W, trastuzumab 6 mg/kg IV (with initial 8-mg/kg IV loading dose) Q3W, \& pertuzumab 420 mg IV (with initial 840-mg IV loading dose) Q3W. Participants who do not achieve pCR have option of receiving blinded atezo+trastuzumab emtansine post surgery for 14 cycles. In response to USM DIL dated 3 Feb 2021 treatment with atezo must be discontinued.
Cyclophosphamide
Cyclophosphamide will be administered as per the schedule specified in the respective arm.
Paclitaxel
Paclitaxel will be administered as per the schedule specified in the respective arm.
Trastuzumab
Trastuzumab will be administered as per the schedule specified in the respective arm.
Pertuzumab
Pertuzumab will be administered as per the schedule specified in the respective arm.
Trastuzumab Emtansine
Participants without pCR have the option of receiving adjuvant atezolizumab/placebo combined with Trastuzumab Emtansine 3.6 mg/kg IV Q3W.
Atezolizumab
Atezolizumab will be administered as per the schedule specified in the respective arm.
Doxorubicin
Doxorubicin will be administered as per the schedule specified in the respective arm.
Placebo + ddAC-PacHP
Participants will receive placebo 840 mg IV Q2W for 4 cycles during neoadjuvant phase with ddAC (doxorubicin 60 mg/m2 \& cyclophosphamide 600 mg/m2 IV), followed by placebo 1200 mg IV Q3W for 4 cycles with paclitaxel 80 mg/m2 IV weekly for 12 continuous weeks, trastuzumab 6 mg/kg IV (with initial 8-mg/kg IV loading dose) Q3W for 4 cycles \& pertuzumab 420 mg IV (with initial 840-mg IV loading dose) Q3W for 4 cycles. During adjuvant phase, participants will continue to receive following study treatments Q3W to complete up to 1 year HER2-target therapy inclusive of therapy given both in neoadjuvant \& adjuvant setting: placebo 1200 mg IV Q3W, trastuzumab 6 mg/kg IV (with initial 8-mg/kg IV loading dose) Q3W, \& pertuzumab 420 mg IV (with initial 840-mg IV loading dose) Q3W. Participants who do not achieve pCR have option of receiving blinded atezolizumab + trastuzumab emtansine post surgery for 14 cycles. In response to USM DIL, dated 3 Feb 2021 treatment with placebo must be discontinued.
Cyclophosphamide
Cyclophosphamide will be administered as per the schedule specified in the respective arm.
Paclitaxel
Paclitaxel will be administered as per the schedule specified in the respective arm.
Trastuzumab
Trastuzumab will be administered as per the schedule specified in the respective arm.
Pertuzumab
Pertuzumab will be administered as per the schedule specified in the respective arm.
Trastuzumab Emtansine
Participants without pCR have the option of receiving adjuvant atezolizumab/placebo combined with Trastuzumab Emtansine 3.6 mg/kg IV Q3W.
Placebo
Placebo matched to atezolizumab will be administered as per the schedule specified in the respective arm.
Doxorubicin
Doxorubicin will be administered as per the schedule specified in the respective arm.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Cyclophosphamide
Cyclophosphamide will be administered as per the schedule specified in the respective arm.
Paclitaxel
Paclitaxel will be administered as per the schedule specified in the respective arm.
Trastuzumab
Trastuzumab will be administered as per the schedule specified in the respective arm.
Pertuzumab
Pertuzumab will be administered as per the schedule specified in the respective arm.
Trastuzumab Emtansine
Participants without pCR have the option of receiving adjuvant atezolizumab/placebo combined with Trastuzumab Emtansine 3.6 mg/kg IV Q3W.
Atezolizumab
Atezolizumab will be administered as per the schedule specified in the respective arm.
Placebo
Placebo matched to atezolizumab will be administered as per the schedule specified in the respective arm.
Doxorubicin
Doxorubicin will be administered as per the schedule specified in the respective arm.
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* Primary breast tumor size of \> 2 cm by any radiographic measurement
* Stage at presentation: T2-T4, N1-N3, M0 as determined by AJCC staging system, 8th edition
* Pathologic confirmation of nodal involvement with malignancy must be determined by fine needle aspiration or core-needle biopsy. Surgical excision of lymph nodes is not permitted.
* Patients with multifocal tumors are eligible provided at least one focus is sampled and centrally confirmed as HER2-positive.
* Patients with multicentric tumors are eligible provided all discrete lesions are sampled and centrally confirmed as HER2-positive.
* Eastern Cooperative Oncology Group Performance Status of 0 or 1
* Baseline LVEF \>= 55% measured by echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scans
* Adequate hematologic and end-organ function obtained within 14 days prior to initiation of study treatment
* For women of childbearing potential: agreement to remain abstinent or use contraceptive methods, and agreement to refrain from donating eggs
* For men: agreement to remain abstinent or use contraceptive measures, and agreement to refrain from donating sperm
Exclusion Criteria
* Stage IV (metastatic) breast cancer
* Patients with synchronous bilateral invasive breast cancer
* Prior systemic therapy for treatment of breast cancer
* Previous therapy with anthracyclines or taxanes for any malignancy
* Ulcerating or inflammatory breast cancer
* Undergone incisional and/or excisional biopsy of primary tumor and/or axillary lymph nodes
* Sentinel lymph node procedure or axillary lymph node dissection prior to initiation of neoadjuvant therapy
* History of other malignancy within 5 years prior to screening, with the exception of those patients who have a negligible risk of metastasis or death
* Cardiopulmonary dysfunction
* Dyspnea at rest
* Active or history of autoimmune disease or immune deficiency
* Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within 5 months after the final dose of atezolizumab/placebo, 6 months after the final dose of doxorubicin, 12 months after the final dose of cyclophosphamide, 6 months after the final dose of paclitaxel, or 7 months after the final dose of trastuzumab, pertuzumab, or trastuzumab emtansine whichever occurs last
* Patients who achieved pCR
* Evidence of clinically evident gross residual or recurrent disease following neoadjuvant therapy and surgery
* Unable to complete surgery with curative intent after conclusion of neoadjuvant systemic therapy
* Patient discontinued treatment with trastuzumab because of toxicity during the neoadjuvant phase of the study
* Clinically significant history of liver disease, including cirrhosis, current alcohol abuse, autoimmune hepatic disorders, or sclerosis cholangitis
* Patients with Grade \>=2 peripheral neuropathy
* Prior treatment with trastuzumab emtansine
18 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Chugai Pharmaceutical
INDUSTRY
Hoffmann-La Roche
INDUSTRY
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Clinical Trials
Role: STUDY_DIRECTOR
Hoffmann-La Roche
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
HCA Midwest Division
Kansas City, Missouri, United States
New York University Medical Center PRIME; NYU Langone Medical Center
New York, New York, United States
Tennessee Oncology - Nashville
Nashville, Tennessee, United States
Hospital Sao Rafael - HSR
Salvador, Estado de Bahia, Brazil
Hospital Araujo Jorge; Departamento de Ginecologia E Mama
Goiânia, Goiás, Brazil
Hospital Nossa Senhora da Conceicao
Porto Alegre, Rio Grande do Sul, Brazil
Hospital Sao Lucas - PUCRS
Porto Alegre, Rio Grande do Sul, Brazil
Hospital Perola Byington
São Paulo, São Paulo, Brazil
Tom Baker Cancer Centre-Calgary
Calgary, Alberta, Canada
BCCA-Vancouver Cancer Centre
Vancouver, British Columbia, Canada
Jewish General Hospital
Montreal, Quebec, Canada
Hopital du Saint Sacrement
Québec, Quebec, Canada
Masarykuv onkologicky ustav
Brno, , Czechia
Fakultni nemocnice Olomouc; Onkologicka klinika
Olomouc, , Czechia
Klinikum Essen-Mitte Ev. Huyssens-Stiftung / Knappschafts GmbH; Klinik für Senologie / Brustzentrum
Essen, , Germany
Praxis für Interdisziplinäre Onkologie und Hämatologie GbR
Freiburg im Breisgau, , Germany
Kooperatives Mammazentrum Hamburg Krankenhaus Jerusalem
Hamburg, , Germany
Sankt Elisabeth Krankenhaus; Gynaekology
Leipzig, , Germany
Rotkreuzklinikum München; Frauenklinik
München, , Germany
Universitätsklinikum Münster; Klinik für Frauenheilkunde und Geburtshilfe
Münster, , Germany
St. Vincenz-Krankenhaus Paderborn; Haus 3 Frauenklinik
Paderborn, , Germany
Universitätsfrauenklinik Ulm; Abteilung Gynäkologie
Ulm, , Germany
Istituto Nazionale Tumori Irccs Fondazione g. PASCALE;U.O.C. Oncologia Medica Senologica
Napoli, Campania, Italy
Università degli Studi Federico II; Clinica di Oncologia Medica
Napoli, Campania, Italy
Irccs Centro Di Riferimento Oncologico (CRO); Dipartimento Di Oncologia Medica
Aviano, Friuli Venezia Giulia, Italy
Policlinico Universitario Agostino Gemelli
Rome, Lazio, Italy
ASST DEGLI SPEDALI CIVILI DI BRESCIA; Oncologia Medica
Brescia, Lombardy, Italy
ASST DI MONZA; Oncologia Medica
Monza, Lombardy, Italy
Istituto Clinico Humanitas;U.O. Oncologia Medica Ed Ematologia
Rozzano, Lombardy, Italy
Fondazione Del Piemonte Per L'oncologia Ircc Di Candiolo; Dipartimento Oncologico
Candiolo, Piedmont, Italy
IOV - Istituto Oncologico Veneto - IRCCS; Oncologia Medica II
Padua, Veneto, Italy
National Hospital Organization Shikoku Cancer Center
Ehime, , Japan
Hiroshima City Hiroshima Citizens Hospital
Hiroshima, , Japan
Hiroshima University Hospital
Hiroshima, , Japan
National Hospital Organization Hokkaido Cancer Center
Hokkaido, , Japan
Hyogo Cancer Center
Hyōgo, , Japan
Kanagawa Cancer Center
Kanagawa, , Japan
Tokai University Hospital
Kanagawa, , Japan
Kumamoto Shinto General Hospital
Kumamoto, , Japan
Fukushima Medical University Hospital
Miyagi, , Japan
Niigata Cancer Center Hospital
Niigata, , Japan
Saitama Medical University International Medical Center
Saitama, , Japan
Toranomon Hospital
Tokyo, , Japan
Showa University Hospital
Tokyo, , Japan
Instytut "Centrum Zdrowia Matki Polki"; Klinika Onkologii
?ód?, , Poland
Narodowy Inst.Onkol.im.Sklodowskiej-Curie Panstw.Inst.Bad Gliwice; Centr.Diagn.i Lecz.Chor.Piersi
Gliwice, , Poland
Regionalny Szpital Specjalistyczny im. W. Bieganskiego; Oddzial Onkologii Klinicznej
Grudzi?dz, , Poland
Szpital Uniwersytecki w Krakowie, Oddzia? Kliniczny Kliniki Onkologii
Krakow, , Poland
Narodowy Inst.Onkologii im.Sklodowskiej-Curie Panstw.Inst.Bad; Klinika Nowtw.Piersi i Chir.Rekonstr
Warsaw, , Poland
FSBI National Medical Research Radiological Center; A. TSYB MEDICAL RADIOLOGICAL RESEARCH CENTER
Obninsk, Kaluga Oblast, Russia
City Clinical Oncology Hospital
Moscow, Moscow Oblast, Russia
SBIH "Moscow Clinical Scientific and Practical Center named after A.S. Loginov of DHM"
Moskva, Moscow Oblast, Russia
Blokhin Cancer Research Center; Combined Treatment
Moskva, Moscow Oblast, Russia
Republican Clinical Oncology Dispensary of Ministry of Healthcare of Tatarstan Republic
Kazan', Tatarstan Republic, Russia
Petrov Research Inst. of Oncology
Saint Petersburg, , Russia
Gachon University Gil Medical Center
Incheon, , South Korea
Korea University Anam Hospital
Seoul, , South Korea
Seoul National University Hospital
Seoul, , South Korea
Samsung Medical Centre; Oncology
Seoul, , South Korea
Hospital Universitari Germans Trias i Pujol; Servicio de Oncologia
Badalona, Barcelona, Spain
Hospital Univ Vall d'Hebron; Servicio de Oncologia
Sant Andreu de la Barca, Barcelona, Spain
Hospital Universitario Virgen de La Arrixaca; Servicio De Oncologia
El Palmar, Murcia, Spain
Clinica Universitaria de Navarra; Servicio de Oncologia
Pamplona, Navarre, Spain
Hospital Clínic i Provincial; Servicio de Hematología y Oncología
Barcelona, , Spain
Complejo Asistencial Universitario De Burgos; Servicio de Oncologia
Burgos, , Spain
Hospital Clinico de Granada; Servicio de Oncologia
Granada, , Spain
Complejo Hospitalario de Jaen-Hospital Universitario Medico Quirurgico; Servicio de Oncologia
Jaén, , Spain
Hospital Universitari Arnau de Vilanova de Lleida; Servicio de Oncologia
Lleida, , Spain
Clinica Universidad de Navarra Madrid; Servicio de Oncología
Madrid, , Spain
Centro Integral Oncologico Clara Campal; Servicio de Oncología
Madrid, , Spain
Hospital Universitario Virgen Macarena; Servicio de Oncologia
Seville, , Spain
Hospital Universitario Virgen del Rocio; Servicio de Oncologia
Seville, , Spain
China Medical University Hospital; Surgery
Taichung, , Taiwan
Mackay Memorial Hospital; Dept of Surgery
Taipei, , Taiwan
Koo Foundation Sun Yat-Sen Cancer Center; Hemato-Oncology
Taipei, , Taiwan
Chang Gung Medical Foundation - Linkou; Dept of Surgery
Taoyuan District, , Taiwan
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
Huober J, Barrios CH, Niikura N, Jarzab M, Chang YC, Huggins-Puhalla SL, Pedrini J, Zhukova L, Graupner V, Eiger D, Henschel V, Gochitashvili N, Lambertini C, Restuccia E, Zhang H; IMpassion050 Trial Investigators. Atezolizumab With Neoadjuvant Anti-Human Epidermal Growth Factor Receptor 2 Therapy and Chemotherapy in Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer: Primary Results of the Randomized Phase III IMpassion050 Trial. J Clin Oncol. 2022 Sep 1;40(25):2946-2956. doi: 10.1200/JCO.21.02772. Epub 2022 Jun 28.
Provided Documents
Download supplemental materials such as informed consent forms, study protocols, or participant manuals.
Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
BO40747
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.