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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

NCT03498716

Description:

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)

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: 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: 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

Clinical Trial IDs

  • ORG STUDY ID: WO39391
  • SECONDARY ID: 2016-003695-47
  • SECONDARY ID: BIG 16-05
  • SECONDARY ID: AFT-27
  • NCT ID: NCT03498716

Conditions

  • Triple Negative Breast Cancer

Interventions

DrugSynonymsArms
AtezolizumabAtezolizumab + Chemotherapy
PaclitaxelAtezolizumab + Chemotherapy
Dose-dense Doxorubicin or dose-dense EpirubicinAtezolizumab + Chemotherapy
CyclophosphamideAtezolizumab + Chemotherapy

Purpose

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)

Trial Arms

NameTypeDescriptionInterventions
Atezolizumab + ChemotherapyExperimentalParticipants 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)
  • Atezolizumab
  • Paclitaxel
  • Dose-dense Doxorubicin or dose-dense Epirubicin
  • Cyclophosphamide
ChemotherapyActive ComparatorChemotherapy 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)
  • Paclitaxel
  • Dose-dense Doxorubicin or dose-dense Epirubicin
  • Cyclophosphamide

Eligibility Criteria

        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
      
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:Randomization until the first occurrence of iDFS event or death, through the end of study (approximately 7 years).
Safety Issue:
Description:iDFS events are defined as follows: Ipsilateral invasive breast tumor recurrence Ipsilateral local-regional invasive breast cancer recurrence Ipsilateral second primary invasive breast cancer Contralateral invasive breast cancer Distant recurrence Death attributable to any cause

Secondary Outcome Measures

Measure:Overall Survival (OS)
Time Frame:Randomization to death from any cause through the end of study (approximately 7 years)
Safety Issue:
Description:
Measure:Disease-Free Survival (DFS)
Time Frame:Randomization until the first occurrence of an DFS event, through the end of study (approximately 7 years)
Safety Issue:
Description:DFS is defined as any event of the primary endpoint and new diagnosis of an ipsilateral or contralateral non-invasive breast cancer.
Measure:Recurrence-Free Interval (RFI)
Time Frame:Randomization until local, regional, or distant recurrence of breast cancer, through the end of study (approximately 7 years)
Safety Issue:
Description:
Measure:Distant RFI
Time Frame:Randomization until distant disease recurrence, through the end of study (approximately 7 years)
Safety Issue:
Description:
Measure:Percentage of participants with adverse events
Time Frame:Baseline to end of study (approximately 7 years)
Safety Issue:
Description:Safety Objective
Measure: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
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure: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).
Safety Issue:
Description: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)
Measure: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).
Safety Issue:
Description: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).

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Hoffmann-La Roche

Last Updated

April 23, 2018