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)
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
- SECONDARY ID:
ALEXANDRA
- NCT ID:
NCT03498716
Conditions
- Triple Negative Breast Cancer
Interventions
Drug | Synonyms | Arms |
---|
Atezolizumab | | Atezolizumab + Chemotherapy |
Paclitaxel | | Atezolizumab + Chemotherapy |
Dose-dense Doxorubicin or dose-dense Epirubicin | | Atezolizumab + Chemotherapy |
Cyclophosphamide | | Atezolizumab + 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
Name | Type | Description | Interventions |
---|
Atezolizumab + Chemotherapy | Experimental | 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) | - Atezolizumab
- Paclitaxel
- Dose-dense Doxorubicin or dose-dense Epirubicin
- Cyclophosphamide
|
Chemotherapy | Active Comparator | 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) | - 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 disease 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: | Recruiting |
Lead Sponsor: | Hoffmann-La Roche |
Last Updated
August 18, 2021