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A Study Comparing Atezolizumab (Anti PD-L1 Antibody) In Combination With Adjuvant Anthracycline/Taxane-Based Chemotherapy Versus Chemotherapy Alone In Patients With Operable Triple-Negative Breast Cancer (IMpassion030)

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ClinicalTrials.gov Identifier: NCT03498716
Recruitment Status : Recruiting
First Posted : April 17, 2018
Last Update Posted : November 26, 2019
Sponsor:
Collaborators:
Breast International Group
Alliance Foundation Trials (AFT)
Institut Jules Bordet/Clinical Trials Support Unit (IJB/CTSU)
Frontier Science and Technology Research Foundation Inc (FS)
Information provided by (Responsible Party):
Hoffmann-La Roche

Tracking Information
First Submitted Date  ICMJE February 28, 2018
First Posted Date  ICMJE April 17, 2018
Last Update Posted Date November 26, 2019
Actual Study Start Date  ICMJE August 2, 2018
Estimated Primary Completion Date January 15, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 12, 2018)
Invasive Disease-Free Survival (iDFS) [ Time Frame: Randomization until the first occurrence of iDFS event or death, through the end of study (approximately 7 years). ]
iDFS events are defined as follows:
  1. Ipsilateral invasive breast tumor recurrence
  2. Ipsilateral local-regional invasive breast cancer recurrence
  3. Ipsilateral second primary invasive breast cancer
  4. Contralateral invasive breast cancer
  5. Distant recurrence
  6. Death attributable to any cause
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03498716 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 31, 2018)
  • Overall Survival (OS) [ Time Frame: Randomization to death from any cause through the end of study (approximately 7 years) ]
  • Disease-Free Survival (DFS) [ Time Frame: Randomization until the first occurrence of an DFS event, through the end of study (approximately 7 years) ]
    DFS is defined as any event of the primary endpoint and new diagnosis of an ipsilateral or contralateral non-invasive breast cancer.
  • Recurrence-Free Interval (RFI) [ Time Frame: Randomization until local, regional, or distant disease recurrence of breast cancer, through the end of study (approximately 7 years) ]
  • Distant RFI [ Time Frame: Randomization until distant disease recurrence, through the end of study (approximately 7 years) ]
  • Percentage of participants with adverse events [ Time Frame: Baseline to end of study (approximately 7 years) ]
    Safety Objective
  • Serum concentration of Atezolizumab [ Time Frame: Pre-infusion (0 hour), 30 minutes post-infusion on Week 1 Day 1 (infusion length = 60 minutes); pre-infusion on Day 1 of Weeks 5, 9, 13, 21, 33 and 45; at treatment discontinuation (up to approximately 1 year), 120 days after last dose ]
  • Invasive Disease-Free Survival (iDFS) in PDL1- Selected Patients [ Time Frame: Randomization until the first occurrence of iDFS event or death, through the end of study (approximately 7 years) ]
  • Invasive Disease-Free Survival (iDFS) in Node- Positive Disease [ Time Frame: Randomization until the first occurrence of iDFS event or death, through the end of study (approximately 7 years) ]
  • Invasive Disease Free Survival (iDFS) including second primary non-breast invasive cancer [ Time Frame: Randomization until the first occurrence of iDFS event or death, through the end of study (approximately 7 years) ]
  • Percentage of Participants with Anti-Drug Antibodies (ADAs) to Atezolizumab [ Time Frame: Updated: Pre-infusion (0 hour) on Day 1 of Weeks 1, 5, 9, 13, 21, 33 and 45; at treatment discontinuation (up to Week 51), 120 days after last dose ]
  • Mean changes from baseline in patient-reported function (role, physical) [ Time Frame: Baseline, Cycle 4 Day 1, Day 1 of every other cycle until Cycle 16 (cycle = 21 days), at the end of treatment/discontinuation visit ((up to approximately 1 year), and during Study Follow-up (up to approximately 7 years). ]
    Mean changes from baseline score in role, physical function will be assessed using the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire - Core 30 (EORTC QLQ-C30)
  • Mean changes from baseline in patient-reported health-related quality of life (HRQoL) [ Time Frame: Time Frame: Baseline, Cycle 4 Day 1, Day 1 of every other cycle until Cycle 16 (cycle = 21 days), at the end of treatment/discontinuation visit (up to approximately 1 year), and during Study Follow-up (up to approximately 7 years). ]
    Mean changes from baseline score in HRQoL will be assessed using the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire - Core 30 (EORTC QLQ-C30).
Original Secondary Outcome Measures  ICMJE
 (submitted: April 12, 2018)
  • Overall Survival (OS) [ Time Frame: Randomization to death from any cause through the end of study (approximately 7 years) ]
  • Disease-Free Survival (DFS) [ Time Frame: Randomization until the first occurrence of an DFS event, through the end of study (approximately 7 years) ]
    DFS is defined as any event of the primary endpoint and new diagnosis of an ipsilateral or contralateral non-invasive breast cancer.
  • Recurrence-Free Interval (RFI) [ Time Frame: Randomization until local, regional, or distant recurrence of breast cancer, through the end of study (approximately 7 years) ]
  • Distant RFI [ Time Frame: Randomization until distant disease recurrence, through the end of study (approximately 7 years) ]
  • Percentage of participants with adverse events [ Time Frame: Baseline to end of study (approximately 7 years) ]
    Safety Objective
  • Serum concentration of Atezolizumab [ Time Frame: Pre-infusion (0 hour), 30 minutes post-infusion on Week 1 Day 1 (infusion length = 60 minutes); pre-infusion on Day 1 of Weeks 5, 9, 13, 21, 33 and 45; at treatment discontinuation (up to approximately 1 year), 120 days after last dose ]
  • Invasive Disease-Free Survival (iDFS) in PDL1- Selected Patients [ Time Frame: Randomization until the first occurrence of iDFS event or death, through the end of study (approximately 7 years) ]
  • Invasive Disease-Free Survival (iDFS) in Node- Positive Disease [ Time Frame: Randomization until the first occurrence of iDFS event or death, through the end of study (approximately 7 years) ]
  • Invasive Disease Free Survival (iDFS) including second primary non-breast invasive cancer [ Time Frame: Randomization until the first occurrence of iDFS event or death, through the end of study (approximately 7 years) ]
  • Percentage of Participants with Anti-Drug Antibodies (ADAs) to Atezolizumab [ Time Frame: Updated: Pre-infusion (0 hour) on Day 1 of Weeks 1, 5, 9, 13, 21, 33 and 45; at treatment discontinuation (up to Week 51), 120 days after last dose ]
  • Mean changes from baseline in patient-reported function (role, physical) [ Time Frame: Baseline, Cycle 4 Day 1, Day 1 of every other cycle until Cycle 16 (cycle = 21 days), at the end of treatment/discontinuation visit ((up to approximately 1 year), and during Study Follow-up (up to approximately 7 years). ]
    Mean changes from baseline score in role, physical function will be assessed using the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire - Core 30 (EORTC QLQ-C30)
  • Mean changes from baseline in patient-reported health-related quality of life (HRQoL) [ Time Frame: Time Frame: Baseline, Cycle 4 Day 1, Day 1 of every other cycle until Cycle 16 (cycle = 21 days), at the end of treatment/discontinuation visit (up to approximately 1 year), and during Study Follow-up (up to approximately 7 years). ]
    Mean changes from baseline score in HRQoL will be assessed using the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire - Core 30 (EORTC QLQ-C30).
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study Comparing Atezolizumab (Anti PD-L1 Antibody) In Combination With Adjuvant Anthracycline/Taxane-Based Chemotherapy Versus Chemotherapy Alone In Patients With Operable Triple-Negative Breast Cancer
Official Title  ICMJE A Phase III, Multicenter, Randomized, Open-Label Study Comparing Atezolizumab (Anti PD-L1 Antibody) in Combination With Adjuvant Anthracycline/Taxane-Based Chemotherapy Versus Chemotherapy Alone in Patients With Operable Triple Negative Breast Cancer
Brief Summary This study will evaluate the efficacy, safety, and pharmacokinetics of adjuvant atezolizumab in combination with paclitaxel, followed by atezolizumab, dose-dense doxorubicin or epirubicin (investigator's choice), and cyclophosphamide, compared with paclitaxel followed by dose-dense doxorubicin or epirubicin (investigator's choice) and cyclophosphamide alone in patients with Stage II-III TNBC (Triple Negative Breast Cancer)
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Triple Negative Breast Cancer
Intervention  ICMJE
  • Drug: Atezolizumab

    Atezolizumab will be administered by IV, 840 mg every 2 weeks, for 10 doses.

    Atezolizumab maintenance will be administered by IV, 1200 mg every 3 weeks to complete 1 year

  • Drug: Paclitaxel
    Paclitaxel will be administered by IV, 80 mg/m^2 every week for 12 weeks.
  • Drug: Dose-dense Doxorubicin or dose-dense Epirubicin

    Dose-dense doxorubicin will be administered by IV, 60 mg/m^2 every 2 weeks for a total of 4 doses.

    Or

    Dose-dense epirubicin will be administered by IV, (90 mg/m^2) every 2 weeks for a total of 4 doses

  • Drug: Cyclophosphamide
    Cyclophosphamide will be administered by IV, 600 mg/m^2 every 2 weeks for 4 doses
Study Arms  ICMJE
  • Experimental: Atezolizumab + Chemotherapy

    Participants will receive atezolizumab (in combination with chemotherapy as described below) every 2 weeks for 10 doses, followed by atezolizumab maintenance therapy every 3 weeks to complete 1 year of treatment from the first dose

    Chemotherapy will consist of paclitaxel every week for 12 weeks, followed by dose-dense doxorubicin +cyclophosphamide or dose-dense epirubicin + cyclophosphamide every 2 weeks, for 4 doses supported with Granulocyte Colony-Stimulating Factor (G-CSF) or Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF)

    Interventions:
    • Drug: Atezolizumab
    • Drug: Paclitaxel
    • Drug: Dose-dense Doxorubicin or dose-dense Epirubicin
    • Drug: Cyclophosphamide
  • Active Comparator: Chemotherapy
    Chemotherapy will consist of paclitaxel every week for 12 weeks, followed by dose-dense doxorubicin +cyclophosphamide or dose-dense epirubicin + cyclophosphamide every 2 weeks, for 4 doses supported with Granulocyte Colony-Stimulating Factor (G-CSF) or Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF)
    Interventions:
    • Drug: Paclitaxel
    • Drug: Dose-dense Doxorubicin or dose-dense Epirubicin
    • Drug: Cyclophosphamide
Publications * Not Provided

*   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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 12, 2018)
2300
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 29, 2024
Estimated Primary Completion Date January 15, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Non-metastatic operable Stage II-III breast cancer
  • Histologically documented TNBC (Triple Negative Breast Cancer)
  • Confirmed tumor PD-L1 evaluation as documented through central testing of a representative tumor tissue specimen
  • Adequately excised: Patients must have undergone either breast-conserving surgery or mastectomy/nipple- or skin-sparing mastectomy
  • Adequate hematologic and end-organ function
  • For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures
  • For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from donating sperm.
  • No more than 8 weeks (56 days) may elapse between definitive breast surgery and randomization.
  • Representative formalin-fixed, paraffin embedded (FFPE) tumor specimen from surgical resection in paraffin blocks (preferred) or at least 25 unstained slides.

Exclusion Criteria

  • Prior history of invasive breast cancer
  • For the currently diagnosed breast cancer, any previous systemic anti-cancer treatment (e.g., neoadjuvant or adjuvant), including, but not limited to, chemotherapy, anti-HER2 therapy.
  • Previous therapy with anthracyclines or taxanes for any malignancy
  • Cardiopulmonary dysfunction
  • Prior malignancies within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcome
  • Active or history of autoimmune disease or immune deficiency
  • History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
  • Urinary outflow obstruction
  • Active tuberculosis
  • Major surgical procedure other than for diagnosis within 4 weeks prior to initiation of study treatment or anticipation of need for a major surgical procedure during study treatment or within 5 months following the last dose of Atezolizumab (for patients randomized to Atezolizumab)
  • Prior allogeneic stem cell or solid organ transplant
  • Treatment with systemic immunosuppressive medications within 2 weeks prior to initiation of study treatment or anticipation of need for systemic immunosuppressive medication 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: Reference Study ID Number: WO39391 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global-roche-genentech-trials@gene.com
Listed Location Countries  ICMJE Argentina,   Australia,   Austria,   Belgium,   Brazil,   China,   Czechia,   Denmark,   France,   Germany,   Hong Kong,   Hungary,   Ireland,   Israel,   Italy,   Japan,   Korea, Republic of,   Mexico,   Peru,   Poland,   Romania,   Russian Federation,   Singapore,   Spain,   Switzerland,   Taiwan,   Thailand,   Ukraine,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03498716
Other Study ID Numbers  ICMJE WO39391
2016-003695-47 ( EudraCT Number )
BIG 16-05 ( Other Identifier: Breast International Group (BIG) )
AFT-27 ( Other Identifier: Alliance Foundation Trials )
ALEXANDRA ( Other Identifier: Breast International Group (BIG) )
Has Data Monitoring Committee Yes
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
  • Breast International Group
  • Alliance Foundation Trials (AFT)
  • Institut Jules Bordet/Clinical Trials Support Unit (IJB/CTSU)
  • Frontier Science and Technology Research Foundation Inc (FS)
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Hoffmann-La Roche
Verification Date November 2019

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