A Study to Investigate Atezolizumab and Chemotherapy Compared With Placebo and Chemotherapy in the Neoadjuvant Setting in Participants With Early Stage Triple Negative Breast Cancer
- Conditions
- Triple-negative Breast Cancer
- Interventions
- Registration Number
- NCT03197935
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
This is a global Phase III, double-blind, randomized, placebo-controlled study designed to evaluate the efficacy and safety of neoadjuvant treatment with atezolizumab (anti-programmed death-ligand 1 \[anti-PD-L1\] antibody) and nab-paclitaxel followed by doxorubicin and cyclophosphamide (nab-pac-AC), or placebo and nab-pac-AC in participants eligible for surgery with initial clinically assessed triple-negative breast cancer (TNBC).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 333
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Atezolizumab and Chemotherapy Pegfilgrastim Participants received atezolizumab (840 milligrams \[mg\]) via intravenous (IV) infusion every 2 weeks in combination with nab-paclitaxel (125 milligrams per square meter \[mg/m\^2\]) via IV infusion every week for 12 weeks, followed by atezolizumab (840 mg) every 2 weeks in combination with doxorubicin (60 mg/m\^2) and cyclophosphamide (600 mg/m\^2) every 2 weeks via IV infusions with filgrastim/pegfilgrastim support for 4 doses. Participants continued to receive unblinded atezolizumab post-surgery at a fixed dose of 1200 mg by IV infusion every 3 weeks for 11 doses, for a total of approximately 12 months of atezolizumab therapy. Placebo and Chemotherapy Pegfilgrastim Participants received placebo matched to atezolizumab via IV infusion every 2 weeks in combination with nab-paclitaxel (125 mg/m\^2) via IV infusion every week for 12 weeks, followed by placebo matched to atezolizumab every 2 weeks in combination with doxorubicin (60 mg/m\^2) and cyclophosphamide (600 mg/m\^2) every 2 weeks via IV infusions with filgrastim/pegfilgrastim support for 4 doses. Participants will be unblinded post-surgery and will continue to be followed. Atezolizumab and Chemotherapy Atezolizumab (MPDL3280A), an engineered anti-PDL1 antibody Participants received atezolizumab (840 milligrams \[mg\]) via intravenous (IV) infusion every 2 weeks in combination with nab-paclitaxel (125 milligrams per square meter \[mg/m\^2\]) via IV infusion every week for 12 weeks, followed by atezolizumab (840 mg) every 2 weeks in combination with doxorubicin (60 mg/m\^2) and cyclophosphamide (600 mg/m\^2) every 2 weeks via IV infusions with filgrastim/pegfilgrastim support for 4 doses. Participants continued to receive unblinded atezolizumab post-surgery at a fixed dose of 1200 mg by IV infusion every 3 weeks for 11 doses, for a total of approximately 12 months of atezolizumab therapy. Atezolizumab and Chemotherapy Nab-paclitaxel Participants received atezolizumab (840 milligrams \[mg\]) via intravenous (IV) infusion every 2 weeks in combination with nab-paclitaxel (125 milligrams per square meter \[mg/m\^2\]) via IV infusion every week for 12 weeks, followed by atezolizumab (840 mg) every 2 weeks in combination with doxorubicin (60 mg/m\^2) and cyclophosphamide (600 mg/m\^2) every 2 weeks via IV infusions with filgrastim/pegfilgrastim support for 4 doses. Participants continued to receive unblinded atezolizumab post-surgery at a fixed dose of 1200 mg by IV infusion every 3 weeks for 11 doses, for a total of approximately 12 months of atezolizumab therapy. Placebo and Chemotherapy Nab-paclitaxel Participants received placebo matched to atezolizumab via IV infusion every 2 weeks in combination with nab-paclitaxel (125 mg/m\^2) via IV infusion every week for 12 weeks, followed by placebo matched to atezolizumab every 2 weeks in combination with doxorubicin (60 mg/m\^2) and cyclophosphamide (600 mg/m\^2) every 2 weeks via IV infusions with filgrastim/pegfilgrastim support for 4 doses. Participants will be unblinded post-surgery and will continue to be followed. Placebo and Chemotherapy Placebo Participants received placebo matched to atezolizumab via IV infusion every 2 weeks in combination with nab-paclitaxel (125 mg/m\^2) via IV infusion every week for 12 weeks, followed by placebo matched to atezolizumab every 2 weeks in combination with doxorubicin (60 mg/m\^2) and cyclophosphamide (600 mg/m\^2) every 2 weeks via IV infusions with filgrastim/pegfilgrastim support for 4 doses. Participants will be unblinded post-surgery and will continue to be followed. Atezolizumab and Chemotherapy Doxorubicin Participants received atezolizumab (840 milligrams \[mg\]) via intravenous (IV) infusion every 2 weeks in combination with nab-paclitaxel (125 milligrams per square meter \[mg/m\^2\]) via IV infusion every week for 12 weeks, followed by atezolizumab (840 mg) every 2 weeks in combination with doxorubicin (60 mg/m\^2) and cyclophosphamide (600 mg/m\^2) every 2 weeks via IV infusions with filgrastim/pegfilgrastim support for 4 doses. Participants continued to receive unblinded atezolizumab post-surgery at a fixed dose of 1200 mg by IV infusion every 3 weeks for 11 doses, for a total of approximately 12 months of atezolizumab therapy. Atezolizumab and Chemotherapy Cyclophosphamide Participants received atezolizumab (840 milligrams \[mg\]) via intravenous (IV) infusion every 2 weeks in combination with nab-paclitaxel (125 milligrams per square meter \[mg/m\^2\]) via IV infusion every week for 12 weeks, followed by atezolizumab (840 mg) every 2 weeks in combination with doxorubicin (60 mg/m\^2) and cyclophosphamide (600 mg/m\^2) every 2 weeks via IV infusions with filgrastim/pegfilgrastim support for 4 doses. Participants continued to receive unblinded atezolizumab post-surgery at a fixed dose of 1200 mg by IV infusion every 3 weeks for 11 doses, for a total of approximately 12 months of atezolizumab therapy. Atezolizumab and Chemotherapy Filgrastim Participants received atezolizumab (840 milligrams \[mg\]) via intravenous (IV) infusion every 2 weeks in combination with nab-paclitaxel (125 milligrams per square meter \[mg/m\^2\]) via IV infusion every week for 12 weeks, followed by atezolizumab (840 mg) every 2 weeks in combination with doxorubicin (60 mg/m\^2) and cyclophosphamide (600 mg/m\^2) every 2 weeks via IV infusions with filgrastim/pegfilgrastim support for 4 doses. Participants continued to receive unblinded atezolizumab post-surgery at a fixed dose of 1200 mg by IV infusion every 3 weeks for 11 doses, for a total of approximately 12 months of atezolizumab therapy. Placebo and Chemotherapy Doxorubicin Participants received placebo matched to atezolizumab via IV infusion every 2 weeks in combination with nab-paclitaxel (125 mg/m\^2) via IV infusion every week for 12 weeks, followed by placebo matched to atezolizumab every 2 weeks in combination with doxorubicin (60 mg/m\^2) and cyclophosphamide (600 mg/m\^2) every 2 weeks via IV infusions with filgrastim/pegfilgrastim support for 4 doses. Participants will be unblinded post-surgery and will continue to be followed. Placebo and Chemotherapy Cyclophosphamide Participants received placebo matched to atezolizumab via IV infusion every 2 weeks in combination with nab-paclitaxel (125 mg/m\^2) via IV infusion every week for 12 weeks, followed by placebo matched to atezolizumab every 2 weeks in combination with doxorubicin (60 mg/m\^2) and cyclophosphamide (600 mg/m\^2) every 2 weeks via IV infusions with filgrastim/pegfilgrastim support for 4 doses. Participants will be unblinded post-surgery and will continue to be followed. Placebo and Chemotherapy Filgrastim Participants received placebo matched to atezolizumab via IV infusion every 2 weeks in combination with nab-paclitaxel (125 mg/m\^2) via IV infusion every week for 12 weeks, followed by placebo matched to atezolizumab every 2 weeks in combination with doxorubicin (60 mg/m\^2) and cyclophosphamide (600 mg/m\^2) every 2 weeks via IV infusions with filgrastim/pegfilgrastim support for 4 doses. Participants will be unblinded post-surgery and will continue to be followed.
- Primary Outcome Measures
Name Time Method Number of Participants With Pathologic Complete Response (pCR) Using American Joint Committee on Cancer (AJCC) Staging System in ITT Population After neoadjuvant study treatment and surgery, up to primary analysis data cut off on 03 ApriI 2020 Number of participants with Pathologic Complete Response (pCR) Using American Joint Committee on Cancer (AJCC) Staging System in ITT Population. pCR is defined as eradication of invasive tumor from both breast and lymph nodes (ypT0/is ypN0). pCR was evaluated for each participant after neoadjuvant study treatment and surgery. Participants whose pCR assessment was missing will be counted as not achieving a pCR.
Number of Participants With pCR in Subpopulation With PD-L1-Positive Tumor Status (Tumor-infiltrating Immune Cell [IC] 1/2/3) Using AJCC Staging System After neoadjuvant study treatment and surgery, up to primary analysis data cut off on 03 ApriI 2020 Number of participants with Pathologic Complete Response (pCR) Using American Joint Committee on Cancer (AJCC) Staging System in the subpopulation with programmed death-ligand1 (PD-L1)-positive tumor status(tumor-infiltrating immune cell \[IC\] IC1/2/3) . pCR is defined as eradication of invasive tumor from both breast and lymph nodes (ypT0/is ypN0). pCR was evaluated for each participant after neoadjuvant study treatment and surgery. Participants whose pCR assessment was missing will be counted as not achieving a pCR.
- Secondary Outcome Measures
Name Time Method Mean Change From Baseline Scores for Function (Role, Physical) and GHS/HRQoL by Cycle and Between Treatment Arms as Assessed by the EORTC QLQ-C30 From randomization and up to study final analysis data cut off on 28 September 2022. Mean change from baseline score in function (role, physical) and global health status(GHS)/ health-related quality of life (HRQoL) by cycle and between treatment arms as assessed by the functional and HRQoL scales of the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core30(QLQ C30).
Event-Free Survival (EFS) in All Participants From randomization and up to study final analysis data cut off on 28 September 2022. Event-free survival (EFS) defined as the time from randomization to the first documented occurrence of disease recurrence, disease progression, or death from any cause in all participants. Recurrent disease includes local, regional, or distant recurrence and contralateral breast cancer. Ipsilateral or contralateral in situ disease and second primary non-breast cancers (including in situ carcinomas and non-melanoma skin cancers) will not be counted as progressive disease or recurrent disease.
Event-Free Survival (EFS) in Subpopulation With PD-L1-Postive Tumor Status From randomization and up to study final analysis data cut off on 28 September 2022. Event-free survival (EFS) defined as the time from randomization to the first documented occurrence of disease recurrence, disease progression, or death from any cause in the subpopulation with PD-L1-positive tumor status. Recurrent disease includes local, regional, or distant recurrence and contralateral breast cancer. Ipsilateral or contralateral in situ disease and second primary non-breast cancers (including in situ carcinomas and non-melanoma skin cancers) will not be counted as progressive disease or recurrent disease.
Disease-Free Survival (DFS) in All Participants Who Undergo Surgery From surgery and up to study final analysis data cut off on 28 September 2022. Disease-free survival (DFS) defined as the time from surgery to the first documented disease recurrence or death from any cause, whichever occurs first. DFS is analyzed with the use of the same methodology as specified for EFS for all participants.
Disease-Free Survival (DFS) in Subpopulation of Participants With PD-L1-Positive Tumor Status Who Undergo Surgery From surgery and up to study final analysis data cut off on 28 September 2022. Disease-free survival (DFS) defined as the time from surgery to the first documented disease recurrence or death from any cause, whichever occurs first. DFS is analyzed with the use of the same methodology as specified for EFS for the subpopulation of participants with PD-L1-positive tumor status.
Overall Survival (OS) in All Participants From randomization and up to study final analysis data cut off on 28 September 2022. Overall survival (OS) defined as the time from randomization to the date of death from any cause in all participants.
Overall Survival (OS) in Subpopulation With PD-L1-Positive Tumor Status From randomization and up to study final analysis data cut off on 28 September 2022. Overall survival (OS) defined as the time from randomization to the date of death from any cause in the subpopulation with PD-L1-positive tumor status.
Minimum Observed Serum Atezolizumab Concentration (Cmin) Pre-dose on Day 1 of Cycles 2, 3, 4, 6, 8, 12, and 16 (cycle length = 28 days from Cycles 1 to 5, and 21 days from Cycles 6 to 16) Minimum observed serum atezolizumab concentration.
Maximum Observed Serum Atezolizumab Concentration (Cmax) Day 1 of Cycle 1 post dose (cycle length = 28 days) Maximum observed atezolizumab concentration (Cmax).
Mean Scores for Function (Role/Physical) and GHS/HRQoL by Cycle and Between Treatment Arms as Assessed by the EORTC QLQ-C30 From randomization and up to study final analysis data cut off on 28 September 2022. Mean score in function (role, physical) and global health status(GHS)/ health-related quality of life (HRQoL) by cycle and between treatment arms as assessed by the functional and HRQoL scales of the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core30(QLQ C30). The score range for each scale and single-item measure is 0 to 100, where higher scores indicate a higher response level (i.e., better functioning, better QoL, worse symptoms).
Percentage of Participants With at Least One Adverse Events (AEs) From randomization and up to study final analysis data cut off on 28 September 2022. Percentage of participants with at least one adverse event.
Percentage of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab Baseline up to approximately 20 months Percentage of participants with anti-drug antibodies (ADAs) to atezolizumab.
Trial Locations
- Locations (68)
Ambulantes Tumorzentrum Spandau; Dres. Benno Mohr und Uwe Peters
🇩🇪Berlin, Germany
Leicester Royal Infirmary
🇬🇧Leicester, United Kingdom
Fiona Stanley Hospital; FSH Cancer Centre Clinical Trials Unit
🇦🇺Bull Creek, Western Australia, Australia
Norwalk Hospital
🇺🇸Norwalk, Connecticut, United States
Clinique Ste-Elisabeth
🇧🇪Namur, Belgium
Vanderbilt Breast Center at One Hundred Oaks
🇺🇸Nashville, Tennessee, United States
Northwest Georgia Oncology Centers, a Service of Wellstar Cobb Hospital
🇺🇸Carrollton, Georgia, United States
Hospital Sao Lucas - PUCRS
🇧🇷Porto Alegre, RS, Brazil
Praxisklinik Krebsheilkunde für Frauen / Brustzentrum (Dres. Kittel/Klare)
🇩🇪Berlin, Germany
Evangelische Kliniken Gelsenkirchen GmbH; Brustzentrum
🇩🇪Gelsenkirchen, Germany
Aichi Cancer Center Hospital
🇯🇵Aichi, Japan
Tokai University Hospital
🇯🇵Kanagawa, Japan
HCA Midwest Division
🇺🇸Kansas City, Missouri, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Tennessee Oncology - Chattanooga; Tennessee Oncology - East Third Street
🇺🇸Chattanooga, Tennessee, United States
Stanford University Medical Center
🇺🇸Palo Alto, California, United States
The Valley Hospital; Valley Medical Group
🇺🇸Paramus, New Jersey, United States
The Center for Cancer and Blood Disorders - Fort Worth
🇺🇸Fort Worth, Texas, United States
Clinicas Oncologicas Integradas - COI
🇧🇷Rio De Janeiro, RJ, Brazil
Monash Medical Centre
🇦🇺Clayton, Victoria, Australia
Cancer Care Northwest
🇺🇸Spokane, Washington, United States
Santa Casa de Misericordia de Salvador
🇧🇷Salvador, BA, Brazil
Hospital Araujo Jorge; Departamento de Ginecologia E Mama
🇧🇷Goiania, GO, Brazil
Sint Augustinus Wilrijk
🇧🇪Wilrijk, Belgium
CETUS Hospital Dia Oncologia
🇧🇷Uberaba, MG, Brazil
UZ Leuven Gasthuisberg
🇧🇪Leuven, Belgium
Hochwaldkrankenhaus
🇩🇪Bad Nauheim, Germany
Hopital du Saint Sacrement
🇨🇦Quebec City, Quebec, Canada
Iop Instituto de Oncologia Do Parana
🇧🇷Curitiba, PR, Brazil
Hospital Nossa Senhora da Conceicao
🇧🇷Porto Alegre, RS, Brazil
Clinica de Pesquisa e Centro de Estudos em Oncologia Ginecologica e Mamaria Ltda
🇧🇷Sao Paulo, SP, Brazil
Jewish General Hospital
🇨🇦Montreal, Quebec, Canada
Luisenkrankenhaus GmbH & Co. KG., Brustzentrum
🇩🇪Düsseldorf, Germany
Hopital Sacre-Coeur Research Centre
🇨🇦Montreal, Quebec, Canada
Diakovere Henriettenstift, Frauenklinik
🇩🇪Hannover, Germany
Kooperatives Mammazentrum Hamburg Krankenhaus Jerusalem
🇩🇪Hamburg, Germany
Onkologische Schwerpunktpraxis Bielefeld
🇩🇪Bielefeld, Germany
Dres. Andreas Köhler und Roswitha Fuchs
🇩🇪Langen, Germany
St. Elisabeth-Krankenhaus, Senologie/Brustzentrum
🇩🇪Leipzig, Germany
Klinik & Poliklinik für Frauenheilkunde und Geburtshilfe, Campus Innenstadt
🇩🇪München, Germany
Universitätsklinikum Münster; Klinik für Frauenheilkunde und Geburtshilfe
🇩🇪Münster, Germany
Medizinisches Versorgungszentrum am Klinikum Oldenburg GmbH
🇩🇪Oldenburg, Germany
Irccs Ospedale San Raffaele
🇮🇹Milano, Lombardia, Italy
Ospedale San Gerardo
🇮🇹Monza, Lombardia, Italy
Fukushima Medical University Hospital
🇯🇵Fukushima, Japan
Kanagawa Cancer Center
🇯🇵Kanagawa, Japan
Azienda ULSS 8 Berica; Oncologia Medica - Ospedlae di Vicenza
🇮🇹Vicenza, Veneto, Italy
Hiroshima City Hiroshima Citizens Hospital; Breast Surgery
🇯🇵Hiroshima, Japan
National Hospital Organization Shikoku Cancer Center
🇯🇵Ehime, Japan
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
National Cancer Center
🇰🇷Goyang-si, Korea, Republic of
National Hospital Organization Osaka National Hospital; Breast Surgery
🇯🇵Osaka, Japan
Narodowy Inst.Onkologii im.Sklodowskiej-Curie Panstw.Inst.Bad; Klinika Nowtw.Piersi i Chir.Rekonstr
🇵🇱Warszawa, Poland
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
St. Luke's Internat. Hospital, Breast Surgical Oncology
🇯🇵Tokyo, Japan
The Cancer Inst. Hosp. of JFCR; Breast Oncology Center
🇯🇵Tokyo, Japan
VETERANS GENERAL HOSPITAL; Department of General Surgery
🇨🇳Taipei, Taiwan
Hospital Universitario 12 de Octubre; Servicio de Oncologia
🇪🇸Madrid, Spain
Hospital Universitario Virgen del Rocio; Servicio de Oncologia
🇪🇸Sevilla, Spain
Dolnoslaskie Centrum Onkologii, Pulmonologii i Hematologii; Oddz. Onkologii Klin. i Chemioterapii
🇵🇱Wroc?aw, Poland
Mackay Memorial Hospital; Dept of Surgery
🇨🇳Taipei, Taiwan
Barts & London School of Med; Medical Oncology
🇬🇧London, United Kingdom
Chang Gung Medical Foundation Linkou Branch
🇨🇳Taoyuan City, Taiwan
Freeman Hospital
🇬🇧Newcastle upon Tyne, United Kingdom
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Mercy Medical Center
🇺🇸Baltimore, Maryland, United States
Tennessee Oncology
🇺🇸Nashville, Tennessee, United States
Cliniques Universitaires St-Luc
🇧🇪Bruxelles, Belgium