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Trial record 1 of 1 for:    NCT04873362
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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 (Astefania)

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ClinicalTrials.gov Identifier: NCT04873362
Recruitment Status : Recruiting
First Posted : May 5, 2021
Last Update Posted : May 11, 2023
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Description
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Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: Atezolizumab Drug: Trastuzumab Emtansine Drug: Placebo Drug: Trastuzumab Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1700 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : May 4, 2021
Estimated Primary Completion Date : December 18, 2025
Estimated Study Completion Date : October 26, 2034

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arms and Interventions
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Arm Intervention/treatment
Active Comparator: Arm A: Placebo + Trastuzumab Emtansine
Participants 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.
 Drug: Trastuzumab Emtansine
Trastuzumab emtansine will be administered at a dose of 3.6 mg/kg Q3W for 14 weeks.
Other Name: Kadcyla, T-DM1, RO5304020

Drug: Placebo
Placebo matched to atezolizumab will be administered at a dose of 1200 mg Q3W for 14 cycles.

Drug: Trastuzumab
Trastuzumab will be used to complete 14 cycles of study treatment if trastuzumab emtansine is discontinued for toxicity not considered to be related to the trastuzumab component of the drug.
Other Name: Herceptin
Experimental: Arm B: Atezolizumab + Trastuzumab Emtansine
Participants 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.
 Drug: Atezolizumab
Atezolizumab will be administered at a dose of 1200 mg every three weeks (Q3W) for 14 cycles.
Other Name: Tecentriq, RO5541267, MPDL3280A

Drug: Trastuzumab Emtansine
Trastuzumab emtansine will be administered at a dose of 3.6 mg/kg Q3W for 14 weeks.
Other Name: Kadcyla, T-DM1, RO5304020

Drug: Trastuzumab
Trastuzumab will be used to complete 14 cycles of study treatment if trastuzumab emtansine is discontinued for toxicity not considered to be related to the trastuzumab component of the drug.
Other Name: Herceptin


Outcome Measures
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Primary Outcome Measures :
  1. Invasive Disease-free Survival (IDFS) [ Time Frame: From randomization up to approximately 6 years ]
    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 :
  1. IDFS Including Second Primary Non-breast Invasive Cancer [ Time Frame: From baseline up to 10 years ]
  2. Disease-free Survival (DFS) [ Time Frame: From baseline up to 10 years ]
  3. Overall Survival (OS) [ Time Frame: From baseline up to 10 years ]
  4. Distant Recurrence-free Interval (DRFI) [ Time Frame: From baseline up to 10 years ]
  5. 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) ]
    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)

  6. 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) ]
    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.

  7. 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) ]
    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.

  8. 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 ]
  9. 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) ]
  10. 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) ]
  11. 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) ]
  12. 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) ]
    DM1 = a thiol-containing maytansinoid anti-microtubule agent; N2'-deacetyl-N2'-(3-mercapto-1-oxopropyl)-maytansine

  13. 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) ]
  14. 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) ]
  15. 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) ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 (prior to neoadjuvant therapy): 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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04873362


Contacts
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Contact: Reference Study ID Number: WO42633 https://forpatients.roche.com/ 888-662-6728 (U.S. and Canada) global-roche-genentech-trials@gene.com

Locations
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Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT04873362    
Other Study ID Numbers: WO42633
2020-003681-40 ( EudraCT Number )
2023-503568-18-00 ( Other Identifier: EU CT )
First Posted: May 5, 2021    Key Record Dates
Last Update Posted: May 11, 2023
Last Verified: May 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Breast Neoplasms
Recurrence
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Disease Attributes
Pathologic Processes
Trastuzumab
Atezolizumab
Ado-Trastuzumab Emtansine
Maytansine
 Antineoplastic Agents, Immunological
Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Immunotoxins
Immunoconjugates
Immunologic Factors
Physiological Effects of Drugs