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
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 2,199
- 试验地点
- 364
- 主要终点
- Invasive Disease-Free Survival (iDFS)
研究概览
简要总结
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)
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- 未提供
研究组 & 干预措施
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)
干预措施: Atezolizumab (Drug)
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)
干预措施: Paclitaxel (Drug)
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)
干预措施: Dose-dense Doxorubicin or dose-dense Epirubicin (Drug)
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)
干预措施: Cyclophosphamide (Drug)
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)
干预措施: Paclitaxel (Drug)
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)
干预措施: Dose-dense Doxorubicin or dose-dense Epirubicin (Drug)
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)
干预措施: Cyclophosphamide (Drug)
结局指标
主要结局
Invasive Disease-Free Survival (iDFS)
时间窗: From randomization until the occurrence of an iDFS event or death from any cause, whichever occurred earlier (up to 5 years)
iDFS was defined as the time from randomization until the date of the first occurrence of one of the following events: Ipsilateral invasive breast tumor recurrence (an invasive breast cancer involving the same breast parenchyma as the original primary lesion); Ipsilateral local-regional invasive breast cancer recurrence (an invasive breast cancer in the axilla, regional lymph nodes, chest wall, \&/or skin of the ipsilateral breast); Ipsilateral second primary invasive breast cancer; Contralateral invasive breast cancer; Distant recurrence (evidence of breast cancer in any anatomic site \[other than the sites mentioned\]) that has either been histologically confirmed \&/or clinically/radiographically diagnosed as recurrent invasive breast cancer; \& Death attributable to any cause, including breast cancer, non-breast cancer, or unknown cause. Analysis used Kaplan-Meier estimates where participants with no events at the time of analysis or no post-baseline information were censored.
次要结局
- Invasive Disease-Free Survival (iDFS) in the Subpopulation With Programmed Death-ligand 1 (PD-L1) Selected Tumor Status (IC1/2/3)(From randomization until the occurrence of an iDFS event or death from any cause, whichever occurred earlier (up to 5 years))
- Recurrence-Free Interval (RFI)(From randomization up to 5 years)
- Disease-Free Survival (DFS)(From randomization up to first disease recurrence or death from any cause (up to 5 years))
- Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) Patient-reported Function (Role Functioning [Q6, Q7])(Baseline (Cycle 1 Day 1), Day 1 of Cycles 4, 6, 8, 10, 12, 14 & 16; end of treatment/discontinuation (approximately at Day 351); Follow up: Months 3 to 48 (Total duration is up to 5 years); Cycles 1-5= 28 day cycles; Cycles 6-16: 21 day cycles)
- Invasive Disease-Free Survival (iDFS) in the Node Positive Subpopulation(From randomization until the occurrence of an iDFS event or death from any cause, whichever occurred earlier (up to 5 years))
- Overall Survival (OS)(From randomization up to death from any cause (up to 5 years))
- Invasive Disease-Free Survival (iDFS) Including Second Primary Non-Breast Invasive Cancer(From randomization up to death from any cause (up to 5 years))
- Distant Recurrence-Free Interval (DRFI)(From randomization up to 5 years)
- Change From Baseline in EORTC QLQ-C30 Global Health Status (GHS) [Q29] and Health-Related Quality of Life (HRQoL) [Q30] Combined Score(Baseline (Cycle 1 Day 1), Day 1 of Cycles 4, 6, 8, 10, 12, 14 & 16; end of treatment/discontinuation (approximately 351 days); Follow up: Months 3 to 48 (Total duration is up to 5 years); Cycles 1-5= 28 day cycles; Cycles 6-16: 21 day cycles)
- Number of Participants With Adverse Events (AE)(Up to 5 years)
- Change From Baseline in EORTC QLQ-C30 Patient-reported Function (Physical Functioning [Q1-Q5])(Baseline (Cycle 1 Day 1), Day 1 of Cycles 4, 6, 8, 10, 12, 14 & 16; end of treatment/discontinuation (approximately at Day 351); Follow up: Months 3 to 48 (Total duration is up to 5 years); Cycles 1-5= 28 day cycles; Cycles 6-16: 21 day cycles)
- Serum Concentration of Atezolizumab(Postdose Day 1 of Cycle 1; Predose Day 1 of Cycles 2, 3, and 4; Predose Cycles 6, 10, and 14; Predose Day 2 of Cycle 16; Cycles 1-5= 28-day cycles; Cycles 6-16: 21-day cycles)
- Percentage of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab(Up to 5 years)