NCT03371017已完成3 期
A Phase III, Randomised, Double-Blind, Placebo-Controlled, Multicentre Study Of The Efficacy And Safety Of Atezolizumab Plus Chemotherapy For Patients With Early Relapsing Recurrent (Inoperable Locally Advanced Or Metastatic) Triple-Negative Breast Cancer
适应症
干预措施
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 595
- 试验地点
- 124
- 主要终点
- Overall Survival (OS) in PD-L1-positive Population
研究概览
简要总结
This study will evaluate the efficacy and safety of atezolizumab plus chemotherapy compared with placebo plus chemotherapy in patients with inoperable recurrent triple-negative breast cancer (TNBC).
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Histologically confirmed triple negative breast cancer (TNBC) that is either locally recurrent, inoperable and cannot be treated with curative intent or is metastatic
- •Documented disease progression occurring within 12 months from the last treatment with curative intent
- •Prior treatment (of early breast cancer) with an anthracycline and taxane
- •Have not received prior chemotherapy or targeted systemic therapy for their locally advanced inoperable or metastatic recurrence. Prior radiation therapy for recurrent disease is permitted
- •Measurable or non-measurable disease, as defined by RECIST 1.1
- •Availability of a representative formalin-fixed, paraffin-embedded (FFPE) tumour block (preferred) or at least 17 unstained slides obtained from relapsed metastatic or locally advanced diseases may be submitted, if clinically feasible, with an associated pathology report, if available. If a fresh tumour sample is not clinically feasible, either the diagnosis sample, the primary surgical resection sample, or the most recent FFPE tumour biopsy sample should be used.
- •Eastern Cooperative Oncology Group performance status 0-1
- •Life expectancy ≥ 12 weeks
- •Adequate haematologic and end-organ function
- •Negative human immunodeficiency virus (HIV) test ---Negative hepatitis B surface antigen (HBsAg) test at screening
- •Negative total hepatitis B core antibody (HBcAb) test at screening, or positive HBcAb test followed by a negative hepatitis B virus (HBV) DNA test at screening
- •The HBV DNA test will be performed only for patients who have a negative HBsAg and a positive HBcAb test.
- •Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening.
- •Women of childbearing potential must agree to remain abstinent (refrain from heterosexual intercourse) or use a contraceptive method with a failure rate of ≤1% per year during the treatment period and for at least 5 months after the last dose of atezolizumab or 6 months after the last dose of capecitabine, whichever is later. In addition, women must refrain from donating eggs during the same time period.
- •Men must agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agree to refrain from donating sperm
- •Inclusion criteria for patients enrolled after the recruitment of all-comers is complete:
- •PD-L1-positive tumour status (assessed centrally prior to randomisation), defined as PD-L1 expression on tumour-infiltrating immune cells (IC) of 1% or greater.
排除标准
- •Spinal cord compression not definitively treated with surgery and/or radiation, or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for > 2 weeks prior to randomisation
- •Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases.
- •Symptomatic or rapid visceral progression
- •No prior treatment with an anthracycline and taxane
- •History of leptomeningeal disease
- •Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently) (patients with indwelling catheters such as PleurX® are allowed)
- •Uncontrolled tumour-related pain
- •Uncontrolled or symptomatic hypercalcemia
- •Malignancies other than TNBC within 5 years prior to randomisation)
- •Significant cardiovascular disease, within 3 months prior to randomisation, unstable arrhythmias, or unstable angina
- •Presence of an abnormal ECG
- •Severe infection requiring oral or IV antibiotics within 4 weeks prior to randomisation, including but not limited to hospitalization for complications of infection, bacteraemia, or severe pneumonia.
- •Current treatment with anti-viral therapy for HBV.
- •Major surgical procedure within 4 weeks prior to randomisation or anticipation of the need for a major surgical procedure during the course of the study other than for diagnosis
- •Treatment with investigational therapy within 28 days prior to randomisation
- •Pregnant or lactating, or intending to become pregnant during or within 5 months after the last dose of atezolizumab, or within 6 months after the last dose of capecitabine, whichever is later.
- •Exclusion Criteria Related to Atezolizumab:
- •History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanised antibodies or fusion proteins
- •Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or to any component of the atezolizumab formulation
- •History of autoimmune disease
- •Prior allogeneic stem cell or solid organ transplantation
- •History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e. bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest computerised tomography (CT) scan History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
- •Active tuberculosis
- •Receipt of a live, attenuated vaccine within 4 weeks prior to randomisation or anticipation that a live, attenuated vaccine will be required during atezolizumab/placebo treatment or within 5 months after the last dose of atezolizumab/placebo
- •Prior treatment with CD137 agonists, anti-PD-1, or anti-PD-L1 therapeutic antibody or pathway targeting agents
- •Treatment with systemic immunostimulatory agents (including but not limited to interferons or interleukin [IL]-2) within 4 weeks or five half-lives of the drug (whichever is longer) prior to randomisation
- •Treatment with systemic corticosteroids or other systemic immunosuppressive medications within 2 weeks prior to start of study treatment, or anticipated requirement for systemic immunosuppressive medications during the trial
- •Exclusion Criteria Related to Capecitabine:
- •Inability to swallow pills
- •Malabsorption syndrome, disease significantly affecting gastrointestinal function, resection of the stomach or small bowel, or ulcerative colitis
- •Known dihydropyrimidine dehydrogenase (DPD) deficiency or history of severe and unexpected reactions to fluoropyrimidine therapy in patients selected to receive capecitabine
- •Exclusion Criteria Related to Carboplatin/Gemcitabine:
- •Hypersensitivity to platinum containing compounds or any component of carboplatin or gemcitabine drug formulations in patients selected to receive carboplatin and Gemcitabine
研究组 & 干预措施
Atezolizumab
Experimental
Participants will receive Atezolizumab on day 1 of each 3-week treatment cycle
干预措施: Atezolizumab (Drug)
Atezolizumab
Experimental
Participants will receive Atezolizumab on day 1 of each 3-week treatment cycle
干预措施: Gemcitabine (Drug)
Atezolizumab
Experimental
Participants will receive Atezolizumab on day 1 of each 3-week treatment cycle
干预措施: Capecitabine (Drug)
Atezolizumab
Experimental
Participants will receive Atezolizumab on day 1 of each 3-week treatment cycle
干预措施: Carboplatin (Drug)
Placebo
Placebo Comparator
Participants will receive Placebo on day 1 of each 3-week treatment cycle
干预措施: Placebo (Drug)
Placebo
Placebo Comparator
Participants will receive Placebo on day 1 of each 3-week treatment cycle
干预措施: Gemcitabine (Drug)
Placebo
Placebo Comparator
Participants will receive Placebo on day 1 of each 3-week treatment cycle
干预措施: Capecitabine (Drug)
Placebo
Placebo Comparator
Participants will receive Placebo on day 1 of each 3-week treatment cycle
干预措施: Carboplatin (Drug)
结局指标
主要结局
Overall Survival (OS) in PD-L1-positive Population
时间窗: Time from randomization to death (Up to 68 months)
OS was defined as time from randomization to death from any cause. Participants without a reported death event at the time of the analysis were censored on the date they were last known to be alive. If no post-baseline data were available, OS was censored at the date of randomization +1 day.
OS in Modified Intent-to-treat (mITT) Population
时间窗: Time from randomization to death (Up to 68 months)
OS was defined as time from randomization to death from any cause. Participants without a reported death event at the time of the analysis were censored on the date they were last known to be alive. If no post-baseline data were available, OS was censored at the date of randomization +1 day.
次要结局
- 12-month Survival Rate in PD-L1-positive Population(12 months)
- 12-month Survival Rate in mITT Population(12 months)
- 18-month Survival Rate in PD-L1-positive Population(18 months)
- 18-month Survival Rate in mITT Population(18 months)
- Progression-free Survival (PFS) in PD-L1-positive Population(Time from randomization to the first occurrence of PD or death (Up to 68 months))
- PFS in mITT Population(Time from randomization to the first occurrence of PD or death (Up to 68 months))
- Objective Response Rate (ORR) in Response-evaluable Population, Subset of PD-L1-positive Population(Baseline up to end of study (Up to 68 months))
- ORR in Response-evaluable Population, Subset of mITT Population(Baseline up to end of study (Up to 68 months))
- Duration of Objective Response (DoR) in DoR-evaluable Population Subset of PD-L1-positive Population(Time from the first occurrence of a documented OR until the date of PD/death (Up to 68 months))
- DoR in DoR-evaluable Population Subset of mITT Population(Time from the first occurrence of a documented OR until the date of PD/death (Up to 68 months))
- Clinical Benefit Rate (CBR) in Response-evaluable Population Subset of PD-L1-positive Population(Up to 68 months)
- CBR in Response-evaluable Population Subset of mITT Population(Up to 68 months)
- Confirmed Objective Response Rate (C-ORR) in Response-evaluable Population Subset of PD-L1-positive Population(Up to 68 months)
- C-ORR in Response-evaluable Population Subset of mITT Population(Up to 68 months)
- DoR for Confirmed Responders (C-DoR) in C-DoR-evaluable Population Subset of PD-L1-positive Population(Time from the first occurrence of a documented OR until the date of PD/death (Up to 68 months))
- C-DoR in C-DoR-evaluable Population Subset of mITT Population(Time from the first occurrence of a documented OR until the date of PD/death (Up to 68 months))
- Time to Confirmed Deterioration (TTD) in Global Health Status/Quality of Life (GHS/QoL) According to the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC QLQ-C30) in PD-L1-positive Population(Up to 68 months)
- TTD in GHS/QoL According to EORTC QLQ-C30 in mITT Population(Up to 68 months)
- Number of Participants With Adverse Events (AEs)(From treatment initiation up to 90 days after last dose (up to 71 months))
- Serum Concentration of Atezolizumab(Pre-dose on Day 1 of Cycles 1, 2, 3 and 4; Post-dose on Day 1 of Cycles 1 and 3 and Treatment Discontinuation Visit (up to 69 months) (1 Cycle= 3 weeks))
- Number of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab(Cycles 1 to 4 and Treatment Discontinuation visit (up to 69 months))
- Number of Participants With PD-L1 Protein Expression in Screening Tumour Tissue and Post-baseline Assessment(Baseline up to 68 months)
研究者
研究点 (124)
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