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Trial record 1 of 1 for:    NCT03197935
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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 (IMpassion031)

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ClinicalTrials.gov Identifier: NCT03197935
Recruitment Status : Active, not recruiting
First Posted : June 23, 2017
Results First Posted : June 2, 2021
Last Update Posted : September 16, 2021
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Tracking Information
First Submitted Date  ICMJE June 21, 2017
First Posted Date  ICMJE June 23, 2017
Results First Submitted Date  ICMJE March 29, 2021
Results First Posted Date  ICMJE June 2, 2021
Last Update Posted Date September 16, 2021
Actual Study Start Date  ICMJE July 24, 2017
Actual Primary Completion Date April 3, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 7, 2021)
  • Number of Participants With Pathologic Complete Response (pCR) Using American Joint Committee on Cancer (AJCC) Staging System in ITT Population [ Time Frame: After neoadjuvant study treatment and surgery, up to 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 [ Time Frame: After neoadjuvant study treatment and surgery, up to 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.
Original Primary Outcome Measures  ICMJE
 (submitted: June 21, 2017)
Percentage of Participants with Pathologic Complete Response (pCR) Using American Joint Committee on Cancer (AJCC) Staging System [ Time Frame: Week 21 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 29, 2021)
  • Event-Free Survival (EFS) in All Participants [ Time Frame: Baseline up to approximately 63 months ]
    Event-free survival (EFS) defined as the time from randomization until documented disease recurrence, progression, or death from any cause in all participants. EFS events covered under "disease recurrence" will include local, regional, or distant recurrence and contralateral breast cancer. Ipsilateral or contralateral in situ disease and second primary non-breast cancers will not be counted as EFS events.
  • Event-Free Survival (EFS) in Subpopulation With PD-L1-Postive Tumor Status [ Time Frame: Baseline up to approximately 63 months ]
    Event-free survival (EFS) defined as the time from randomization until documented disease recurrence, progression, or death from any cause in the subpopulation with PD-L1-positive tumor status. EFS events covered under "disease recurrence" will include local, regional, or distant recurrence and contralateral breast cancer. Ipsilateral or contralateral in situ disease and second primary non-breast cancers will not be counted as EFS events.
  • Disease-Free Survival (DFS) in All Participants Who Undergo Surgery [ Time Frame: Baseline up to approximately 63 months ]
    Disease-free survival (DFS) defined as the time from surgery until documented disease recurrence or death from any cause in all patients (ITT population) who undergo surgery.
  • Disease-Free Survival (DFS) in Subpopulation of Participants With PD-L1-Positive Tumor Status Who Undergo Surgery [ Time Frame: Baseline up to approximately 63 months ]
    Disease-free survival (DFS) defined as the time from surgery until documented disease recurrence or death from any cause in the subpopulation of participants with PD-L1-positive tumor status who undergo surgery.
  • Overall Survival (OS) in All Participants [ Time Frame: Baseline up to approximately 63 months ]
    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 [ Time Frame: Baseline up to approximately 63 months ]
    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.
  • Mean Scores for Function (Role/Physical) and GHS/HRQoL by Cycle and Between Treatment Arms as Assessed by the EORTC QLQ-C30 [ Time Frame: Baseline (Cycle 1 Day 1), on Day 1 of every cycle (C) thereafter (C=28 days from C1 to 5, and 21 days from C6 to 16), at Study Drug Completion/Early Discontinuation, Survival Follow-Up Months 3, 6, 9, 12, 18 and 24 (up to approximately 63 months) ]
    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 EORTC QLQ-C30 includes five functional scales; a global health status (GHS)/quality of life (QoL) scale; and items measuring fatigue, pain, nausea and vomiting, dyspnea, appetite loss, sleep disturbance, constipation, diarrhea, and financial difficulties. 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).
  • 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 [ Time Frame: Baseline (Cycle 1 Day 1), and on Day 1 of every cycle (C) thereafter (C length=28 days from C1 to 5, and 21 days from C6 to 16), at Study Drug Completion/Early Termination, Survival Follow-Up Months 12, 18, and 24 (up to approximately 63 months) ]
    Mean change from baseline score in function (role, physical) andglobal 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). Note: Cycle=C; Day=D.
  • Percentage of Participants With Adverse Events (AEs) [ Time Frame: Baseline up to approximately 63 months ]
    Percentage of participants with adverse events.
  • Minimum Observed Serum Atezolizumab Concentration (Cmin) [ Time Frame: 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) [ Time Frame: Day 1 of Cycle 1 post dose (cycle length = 28 days) ]
    Maximum observed atezolizumab concentration (Cmax).
  • Percentage of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab [ Time Frame: Baseline up to approximately 20 months ]
    Percentage of participants with anti-drug antibodies (ADAs) to atezolizumab.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 21, 2017)
  • Percentage of Participants with pCR in Subpopulation with PD-L1-Selected Tumor Status (tumor-infiltrating immune cell [IC] 1/2/3) Using AJCC Staging System [ Time Frame: Week 21 ]
  • Event-Free Survival (EFS) Using AJCC Staging System [ Time Frame: From randomization until documented disease recurrence, progression, or death from any cause (up to approximately 51 months) ]
  • Overall survival (OS) [ Time Frame: From randomization to the date of death from any cause (up to approximately 51 months) ]
  • Changes From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) Score [ Time Frame: Baseline (Cycle 1 Day 1), and on Day 1 of every cycle thereafter (cycle length = 28 days from Cycles 1 to 5, and 21 days from Cycles 6 to 16) (up to approximately 15 months) ]
  • Percentage of Participants with Adverse Events (AEs) [ Time Frame: Baseline up to approximately 51 months ]
  • Serum Concentration of Atezolizumab [ Time Frame: Pre-infusion (0 hour), 30 minutes post-infusion on Week 1 Day 1; pre-infusion on Day 1 of Weeks 5, 9, 13, 21, 27, 39, 51; at treatment discontinuation (last dose = up to 15 months), 120 days after last dose (infusion length = 60 minutes) ]
  • Percentage of Participants with Anti-Drug Antibodies (ADAs) to Atezolizumab [ Time Frame: Pre-infusion (0 hour) on Day 1 of Weeks 1, 5, 9, 13, 21, 27, 39, 51; at treatment discontinuation (last dose = up to 15 months), 120 days after last dose (infusion length = 60 minutes) ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE A Phase III Randomized Study to Investigate the Efficacy and Safety of Atezolizumab (Anti-PD-L1 Antibody) in Combination With Neoadjuvant Anthracycline/Nab-Paclitaxel-Based Chemotherapy Compared With Placebo and Chemotherapy in Patients With Primary Invasive Triple-Negative Breast Cancer
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Triple-negative Breast Cancer
Intervention  ICMJE
  • Drug: Atezolizumab (MPDL3280A), an engineered anti-PDL1 antibody
    Atezolizumab was administered as per schedule described in respective arm.
  • Drug: Placebo
    Placebo matched to atezolizumab was administered as per schedule described in respective arm.
  • Drug: Nab-paclitaxel
    Nab-paclitaxel was administered as per schedule described in the arms.
  • Drug: Doxorubicin
    Doxorubicin was administered as per schedule described in the arms.
  • Drug: Cyclophosphamide
    Cyclophosphamide was administered as per schedule described in the arms.
  • Drug: Filgrastim
    Filgrastim was administered according to local prescribing information as determined by the Investigator for 4 doses after completion of initial 12 weeks.
  • Drug: Pegfilgrastim
    Pegfilgrastim was administered according to local prescribing information as determined by the Investigator for 4 doses after completion of initial 12 weeks.
Study Arms  ICMJE
  • Experimental: Atezolizumab and Chemotherapy
    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.
    Interventions:
    • Drug: Atezolizumab (MPDL3280A), an engineered anti-PDL1 antibody
    • Drug: Nab-paclitaxel
    • Drug: Doxorubicin
    • Drug: Cyclophosphamide
    • Drug: Filgrastim
    • Drug: Pegfilgrastim
  • Placebo Comparator: Placebo and Chemotherapy
    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.
    Interventions:
    • Drug: Placebo
    • Drug: Nab-paclitaxel
    • Drug: Doxorubicin
    • Drug: Cyclophosphamide
    • Drug: Filgrastim
    • Drug: Pegfilgrastim
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: March 29, 2021)
333
Original Estimated Enrollment  ICMJE
 (submitted: June 21, 2017)
204
Estimated Study Completion Date  ICMJE October 21, 2022
Actual Primary Completion Date April 3, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion criteria:

  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Histologically documented TNBC (negative human epidermal growth factor receptor 2 [HER2], estrogen receptor [ER], and progesterone receptor [PgR] status)
  • Confirmed tumor programmed death-ligand 1 (PD-L1) evaluation as documented through central testing of a representative tumor tissue specimen
  • Primary breast tumor size of greater than (>) 2 centimeters (cm) by at least one radiographic or clinical measurement
  • Stage at presentation: cT2-cT4, cN0-cN3, cM0
  • Participant agreement to undergo appropriate surgical management including axillary lymph node surgery and partial or total mastectomy after completion of neoadjuvant treatment
  • Baseline left ventricular ejection fraction (LVEF) greater than or equal to (>=) 53 percent (%) measured by echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scans
  • Adequate hematologic and end-organ function
  • Representative formalin-fixed, paraffin-embedded (FFPE) tumor specimen in paraffin blocks (preferred) or at least 20 unstained slides, with an associated pathology report documenting ER, PgR, and HER2 negativity
  • For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agreement to refrain from donating eggs
  • For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from donating sperm
  • Women who are not postmenopausal or have undergone a sterilization procedure must have a negative serum pregnancy test result within 14 days prior to initiation of study drug

Exclusion criteria:

  • Prior history of invasive breast cancer
  • Stage 4 (metastatic) breast cancer
  • Prior systemic therapy for treatment and prevention of breast cancer
  • Previous therapy with anthracyclines or taxanes for any malignancy
  • History of ductal carcinoma in situ (DCIS), except for participants treated exclusively with mastectomy >5 years prior to diagnosis of current breast cancer
  • History of pleomorphic lobular carcinoma in situ (LCIS), except for participants surgically managed >5 years prior to diagnosis of current breast cancer
  • Bilateral breast cancer
  • Undergone incisional and/or excisional biopsy of primary tumor and/or axillary lymph nodes
  • 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 with a negligible risk of metastasis or death
  • Cardiopulmonary dysfunction
  • History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
  • Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells
  • Known allergy or hypersensitivity to the components of the formulations of atezolizumab, nab-paclitaxel, cyclophosphamide, or doxorubicin, filgrastim or pegfilgrastim
  • Active or history of autoimmune disease or immune deficiency diseases except history of autoimmune-related hypothyroidism, controlled Type 1 diabetes mellitus, and dermatologic manifestations of eczema, psoriasis, lichen simplex chronicus, or vitiligo (e.g., participants with psoriatic arthritis are excluded)
  • History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted
  • Positive human immunodeficiency virus (HIV) test at screening
  • Active hepatitis B and hepatitis C virus infection
  • Active tuberculosis
  • Severe infections within 4 weeks prior to initiation of study treatment, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia
  • Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment, except prophylactic antibiotics
  • Major surgical procedure within 4 weeks prior to initiation of study treatment or anticipation of need for a major surgical procedure during the course of the study
  • Prior allogeneic stem cell or solid organ transplantation
  • Administration of a live attenuated vaccine within 4 weeks prior to initiation of study treatment or anticipation of need for such a vaccine during the study
  • Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the participant at high risk from treatment complications
  • Prior treatment with cluster of differentiation 137 (CD137) agonists or immune checkpoint-blockade therapies, including anti-cluster of differentiation 40 (anti-CD40), anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4), anti-programmed death-1 (anti-PD-1), and anti-PD-L1 therapeutic antibodies
  • Treatment with systemic immunostimulatory agents within 4 weeks or 5 half-lives of the drug, whichever is longer, prior to initiation of study treatment
  • Treatment with systemic immunosuppressive medications within 2 weeks prior to initiation of study treatment or anticipation of need for systemic immunosuppressive medications during the study
  • History of cerebrovascular accident within 12 months prior to randomization
  • Pregnant or lactating, or intending to become pregnant during the study
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Belgium,   Brazil,   Canada,   Germany,   Italy,   Japan,   Korea, Republic of,   Poland,   Spain,   Taiwan,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03197935
Other Study ID Numbers  ICMJE WO39392
2016-004734-22 ( EudraCT Number )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Hoffmann-La Roche
Study Sponsor  ICMJE Hoffmann-La Roche
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Hoffmann-La Roche
Verification Date September 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP