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A Study Evaluating the Efficacy and Safety of Adjuvant Atezolizumab or Placebo and Trastuzumab Emtansine for Participants With HER2-Positive Breast Cancer at High Risk of Recurrence Following Preoperative Therapy

NCT04873362

Description:

This is a Phase III, two-arm, randomized, double-blind placebo-controlled study in participants with HER2-positive primary breast cancer who have received preoperative chemotherapy and HER2-directed therapy, including trastuzumab followed by surgery, with a finding of residual invasive disease in the breast and/or axillary lymph nodes.

Related Conditions:
  • Invasive Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: A Study Evaluating the Efficacy and Safety of Adjuvant Atezolizumab or Placebo and Trastuzumab Emtansine for Participants With HER2-Positive Breast Cancer at High Risk of Recurrence Following Preoperative Therapy
  • Official Title: A Phase III, Randomized, Double-Blind, Placebo-Controlled Clinical Trial to Evaluate the Efficacy and Safety of Adjuvant Atezolizumab or Placebo and Trastuzumab Emtansine for HER2-Positive Breast Cancer at High Risk of Recurrence Following Preoperative Therapy

Clinical Trial IDs

  • ORG STUDY ID: WO42633
  • SECONDARY ID: 2020-003681-40
  • NCT ID: NCT04873362

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
AtezolizumabTecentriq, RO5541267, MPDL3280AArm B: Atezolizumab + Trastuzumab Emtansine
Trastuzumab EmtansineKadcyla, T-DM1, RO5304020Arm A: Placebo + Trastuzumab Emtansine
PlaceboArm A: Placebo + Trastuzumab Emtansine
TrastuzumabHerceptinArm A: Placebo + Trastuzumab Emtansine

Purpose

This is a Phase III, two-arm, randomized, double-blind placebo-controlled study in participants with HER2-positive primary breast cancer who have received preoperative chemotherapy and HER2-directed therapy, including trastuzumab followed by surgery, with a finding of residual invasive disease in the breast and/or axillary lymph nodes.

Trial Arms

NameTypeDescriptionInterventions
Arm A: Placebo + Trastuzumab EmtansineActive ComparatorParticipants will receive an intravenous (IV) infusion of placebo prior to the IV infusion of trastuzumab emtansine on Day 1 of each 21-day cycle for a total of 14 cycles.
  • Trastuzumab Emtansine
  • Placebo
  • Trastuzumab
Arm B: Atezolizumab + Trastuzumab EmtansineExperimentalParticipants will receive an IV infusion of atezolizumab prior to the IV infusion of trastuzumab emtansine on Day 1 of each 21-day cycle for a total of 14 cycles.
  • Atezolizumab
  • Trastuzumab Emtansine
  • Trastuzumab

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically confirmed invasive breast carcinoma

          -  Centrally-confirmed human epidermal growth factor receptor 2 (HER2)-positive invasive
             breast cancer

          -  Centrally confirmed PD-L1 and hormone receptor status

          -  Clinical stage at disease presentation: cT4/anyN/M0, any cT/N2-3/M0, or cT1-3/N0-1/M0
             (participants with cT1mi/T1a/T1b/N0 are not eligible)

          -  Completion of pre-operative systemic chemotherapy including at least 9 weeks of taxane
             and 9 weeks of trastuzumab (anthracycline and/or additional HER2-targeted agents are
             permitted)

          -  <=12 weeks between primary surgery and randomization

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1

          -  Screening left ventricular ejection fraction (LVEF) >= 50% and no decrease in LVEF by
             >15% from the pre-chemotherapy LVEF. If no pre-chemotherapy LVEF, screening LVEF >=
             55%

          -  Life expectancy >= 6 months

          -  Adequate hematologic and end organ function

        Exclusion Criteria:

          -  Stage IV breast cancer

          -  An overall response of disease progression according to the investigator at the
             conclusion of preoperative systemic therapy

          -  Prior treatment with T-DM1, or atezolizumab, or other immune checkpoint inhibitors

          -  History of exposure to various cumulative doses of anthracyclines

          -  History of other malignancy within 5 years prior to screening, except for
             appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma,
             Stage I uterine cancer, or ductal carcinoma in situ (DCIS)

          -  Current grade >=2 peripheral neuropathy

          -  History of idiopathic pulmonary fibrosis, organizing pneumonia, or pneumonitis

          -  History of or active autoimmune disease or immune deficiency

          -  Treatment with immunostimulatory or immunosuppressive agents

          -  Cardiopulmonary dysfunction

          -  Any known active liver disease
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Invasive Disease-free Survival (IDFS)
Time Frame:From randomization up to approximately 6 years
Safety Issue:
Description:IDFS event is defined as the time from randomization to the first occurrence of the following events: ipsilateral invasive breast tumor recurrence, ipsilateral local-regional invasive breast cancer recurrence, contralateral invasive breast cancer, distant recurrence, death from any cause.

Secondary Outcome Measures

Measure:IDFS Including Second Primary Non-breast Invasive Cancer
Time Frame:From baseline up to 10 years
Safety Issue:
Description:
Measure:Disease-free Survival (DFS)
Time Frame:From baseline up to 10 years
Safety Issue:
Description:
Measure:Overall Survival (OS)
Time Frame:From baseline up to 10 years
Safety Issue:
Description:
Measure:Distant Recurrence-free Interval (DRFI)
Time Frame:From baseline up to 10 years
Safety Issue:
Description:
Measure:Number of Participants with Clinically Meaningful Deterioration in Global Health Status/Quality of Life (GHS/QoL) Physical, Role, and Cognitive Function
Time Frame:From baseline until 2 years after study treatment completion/discontinuation visit (approximately 3 years)
Safety Issue:
Description:Clinically Meaningful Deterioration will be Measured by Scales of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire for Cancer (EORTC QLQ C30)
Measure:Mean Absolute Scores in GHS/QoL, Physical, Role, and Cognitive Function, as Assessed Using the EORTC QLQ-C30
Time Frame:From baseline until 2 years after study treatment completion/discontinuation visit (approximately 3 years)
Safety Issue:
Description:The European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 Questionnaire (EORTC QLQ-C30) is a self-reported measure. Functioning and symptoms items are scored on a 4-point scale: 1=Not at all, 2=A little, 3=Quite a bit, 4=Very much. GHS and QoL items are scored on a 7-point scale: 1=Very poor, 2, 3, 4, 5, 6, 7=Excellent. Scores will be transformed to a range of 0 to 100, with higher scores (i.e. closer to 100) reflecting better functioning, better GHS/QoL, and worse symptoms.
Measure:Mean Change From Baseline Scores in GHS/QoL, Physical, Role, and Cognitive Function, as Assessed Using the EORTC QLQ-C30
Time Frame:From baseline until 2 years after study treatment completion/discontinuation visit (approximately 3 years)
Safety Issue:
Description:The European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 Questionnaire (EORTC QLQ-C30) is a self-reported measure. Functioning and symptoms items are scored on a 4-point scale: 1=Not at all, 2=A little, 3=Quite a bit, 4=Very much. GHS and QoL items are scored on a 7-point scale: 1=Very poor, 2, 3, 4, 5, 6, 7=Excellent. Scores will be transformed to a range of 0 to 100, with higher scores (i.e. closer to 100) reflecting better functioning, better GHS/QoL, and worse symptoms.
Measure:Percentage of Participants with Adverse Events (AEs) According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0)
Time Frame:From baseline up to 10 years
Safety Issue:
Description:
Measure:Maximum Serum Concentrations (Cmax) for Atezolizumab
Time Frame:Day 1 of Cycles 1 and 4 pre-infusion, Day 1 of Cycles 1 and 4 after 30 minutes post-infusion, Day 1 of Cycles 2, 3 and 8 pre-infusion (cycle=21 days) and at study treatment completion/discontinuation visit (approximately 11 months after Cycle 1 Day 1)
Safety Issue:
Description:
Measure:Cmax for Trastuzumab Emtansine
Time Frame:Day 1 of Cycles 1 and 4 pre-infusion, Day 1 of Cycles 1 and 4 after 30 minutes post-infusion, (cycle=21 days) and at study treatment completion/discontinuation visit (approximately 11 months after Cycle 1 Day 1)
Safety Issue:
Description:
Measure:Cmax for Total Trastuzumab
Time Frame:Day 1 of Cycles 1 and 4 pre-infusion, Day 1 of Cycles 1 and 4 after 30 minutes post-infusion, (cycle=21 days) and at study treatment completion/discontinuation visit (approximately 11 months after Cycle 1 Day 1)
Safety Issue:
Description:
Measure:Cmax for DM1
Time Frame:Day 1 of Cycles 1 and 4 pre-infusion, Day 1 of Cycles 1 and 4 after 30 minutes post-infusion, (cycle=21 days) and at study treatment completion/discontinuation visit (approximately 11 months after Cycle 1 Day 1)
Safety Issue:
Description:DM1 = a thiol-containing maytansinoid anti-microtubule agent; N2'-deacetyl-N2'-(3-mercapto-1-oxopropyl)-maytansine
Measure:Minimum Serum Concentrations (Cmin) for Atezolizumab
Time Frame:Day 1 of Cycles 1 and 4 pre-infusion, Day 1 of Cycles 1 and 4 after 30 minutes post-infusion, Day 1 of Cycles 2, 3 and 8 (cycle=21 days) and at study treatment completion/discontinuation visit (approximately 11 months after Cycle 1 Day 1)
Safety Issue:
Description:
Measure:Percentage of Participants with Anti-drug Antibodies (ADAs) to Atezolizumab
Time Frame:Day 1 of Cycles 1 and 4 pre-infusion, Day 1 of Cycles 1 and 4 after 30 minutes post-infusion, Day 1 of Cycles 2, 3 and 8 (cycle=21 days) and at study treatment completion/discontinuation visit (approximately 11 months after Cycle 1 Day 1)
Safety Issue:
Description:
Measure:Percentage of Participants with ADAs to Trastuzumab Emtansine
Time Frame:Day 1 of Cycles 1 and 4 pre-infusion, Day 1 of Cycles 1 and 4 after 30 minutes post-infusion, (cycle=21 days) and at study treatment completion/discontinuation visit (approximately 11 months after Cycle 1 Day 1)
Safety Issue:
Description:

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Hoffmann-La Roche

Last Updated

July 9, 2021