A Phase Ib/II Randomized Study of BI 836845 in Combination With Exemestane and Everolimus Versus Exemestane and Everolimus Alone in Women With Locally Advanced or Metastatic Breast Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 164
- 试验地点
- 38
- 主要终点
- Progression-free Survival (PFS) - Phase II Part
研究概览
简要总结
Phase Ib / II study to determine the Maximum Tolerated Dose and Recommended Phase II Dose, and to evaluate the safety and antitumour activity, of BI 836845 and everolimus in combination with exemestane in women with HR+/HER2- advanced 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 99 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
everolimus 10 mg + exemestane 25 mg - Phase II
Subjects received a single oral dose once daily (qd) of 2x 5 mg (10 mg total) tablets of everolimus and 1 tablet of 25 mg exemestane starting on Day 1 continously until disease progression, intolerable AEs or other reason necessitating withdrawal.
干预措施: Everolimus (Drug)
everolimus 10 mg + exemestane 25 mg - Phase II
Subjects received a single oral dose once daily (qd) of 2x 5 mg (10 mg total) tablets of everolimus and 1 tablet of 25 mg exemestane starting on Day 1 continously until disease progression, intolerable AEs or other reason necessitating withdrawal.
干预措施: Exemestane (Drug)
xentuzumab (BI 836845) 1000 mg + everolimus 10 mg + exemestane 25 mg - Phase II
Subjects received a single dose of 1000 milligram (mg) BI 836845 (xentuzumab) as a 1 hour (h) intravenous infusion once a week on Day 1, 8, 15 and 22 in a 28-day course until disease progression, intolerable AEs or other reason necessitating withdrawal. Subjects also received a single oral dose once daily (qd) of 2x 5 mg (10 mg total) tablets of everolimus and 1 tablet of 25 mg exemestane starting on Day 1 continously until disease progression, intolerable AEs or other reason necessitating withdrawal. Administration of xentuzumab was stopped after 28th October 2016, and participants in this group who remained in the trial could continue with everolimus 10 mg + exemestane 25 mg.
干预措施: Everolimus (Drug)
xentuzumab (BI 836845) 1000 mg + everolimus 10 mg + exemestane 25 mg - Phase II
Subjects received a single dose of 1000 milligram (mg) BI 836845 (xentuzumab) as a 1 hour (h) intravenous infusion once a week on Day 1, 8, 15 and 22 in a 28-day course until disease progression, intolerable AEs or other reason necessitating withdrawal. Subjects also received a single oral dose once daily (qd) of 2x 5 mg (10 mg total) tablets of everolimus and 1 tablet of 25 mg exemestane starting on Day 1 continously until disease progression, intolerable AEs or other reason necessitating withdrawal. Administration of xentuzumab was stopped after 28th October 2016, and participants in this group who remained in the trial could continue with everolimus 10 mg + exemestane 25 mg.
干预措施: Exemestane (Drug)
xentuzumab (BI 836845) 1000 mg + everolimus 10 mg + exemestane 25 mg - Phase II
Subjects received a single dose of 1000 milligram (mg) BI 836845 (xentuzumab) as a 1 hour (h) intravenous infusion once a week on Day 1, 8, 15 and 22 in a 28-day course until disease progression, intolerable AEs or other reason necessitating withdrawal. Subjects also received a single oral dose once daily (qd) of 2x 5 mg (10 mg total) tablets of everolimus and 1 tablet of 25 mg exemestane starting on Day 1 continously until disease progression, intolerable AEs or other reason necessitating withdrawal. Administration of xentuzumab was stopped after 28th October 2016, and participants in this group who remained in the trial could continue with everolimus 10 mg + exemestane 25 mg.
干预措施: BI 836845 (Drug)
xentuzumab (BI 836845) 750 mg + everolimus 10 mg + exemestane 25 mg - Phase Ib
Subjects received a single dose of 750 milligram (mg) BI 836845 (xentuzumab) as a 1 hour (h) intravenous infusion once a week on Day 1, 8, 15 and 22 in a 28- day course until disease progression, intolerable AEs or other reason necessitating withdrawal. Subjects also received a single oral dose once daily (qd) of 2x 5 mg (10 mg total) tablets of everolimus and 1 tablet of 25 mg exemestane starting 7 days before first administration of BI 836845 (xentuzumab) continously until disease progression, intolerable AEs or other reason necessitating withdrawal.
干预措施: Everolimus (Drug)
xentuzumab (BI 836845) 750 mg + everolimus 10 mg + exemestane 25 mg - Phase Ib
Subjects received a single dose of 750 milligram (mg) BI 836845 (xentuzumab) as a 1 hour (h) intravenous infusion once a week on Day 1, 8, 15 and 22 in a 28- day course until disease progression, intolerable AEs or other reason necessitating withdrawal. Subjects also received a single oral dose once daily (qd) of 2x 5 mg (10 mg total) tablets of everolimus and 1 tablet of 25 mg exemestane starting 7 days before first administration of BI 836845 (xentuzumab) continously until disease progression, intolerable AEs or other reason necessitating withdrawal.
干预措施: Exemestane (Drug)
xentuzumab (BI 836845) 750 mg + everolimus 10 mg + exemestane 25 mg - Phase Ib
Subjects received a single dose of 750 milligram (mg) BI 836845 (xentuzumab) as a 1 hour (h) intravenous infusion once a week on Day 1, 8, 15 and 22 in a 28- day course until disease progression, intolerable AEs or other reason necessitating withdrawal. Subjects also received a single oral dose once daily (qd) of 2x 5 mg (10 mg total) tablets of everolimus and 1 tablet of 25 mg exemestane starting 7 days before first administration of BI 836845 (xentuzumab) continously until disease progression, intolerable AEs or other reason necessitating withdrawal.
干预措施: BI 836845 (Drug)
xentuzumab (BI 836845) 1000 mg + everolimus 10 mg + exemestane 25 mg - Phase Ib
Subjects received a single dose of 1000 milligram (mg) BI 836845 (xentuzumab) as a 1 hour (h) intravenous infusion once a week on Day 1, 8, 15 and 22 in a 28-day course until disease progression, intolerable AEs or other reason necessitating withdrawal. Subjects also received a single oral dose once daily (qd) of 2x 5 mg (10 mg total) tablets of everolimus and 1 tablet of 25 mg exemestane starting 7 days before first administration of BI 836845 (xentuzumab) continously until disease progression, intolerable AEs or other reason necessitating withdrawal.
干预措施: Everolimus (Drug)
xentuzumab (BI 836845) 1000 mg + everolimus 10 mg + exemestane 25 mg - Phase Ib
Subjects received a single dose of 1000 milligram (mg) BI 836845 (xentuzumab) as a 1 hour (h) intravenous infusion once a week on Day 1, 8, 15 and 22 in a 28-day course until disease progression, intolerable AEs or other reason necessitating withdrawal. Subjects also received a single oral dose once daily (qd) of 2x 5 mg (10 mg total) tablets of everolimus and 1 tablet of 25 mg exemestane starting 7 days before first administration of BI 836845 (xentuzumab) continously until disease progression, intolerable AEs or other reason necessitating withdrawal.
干预措施: Exemestane (Drug)
xentuzumab (BI 836845) 1000 mg + everolimus 10 mg + exemestane 25 mg - Phase Ib
Subjects received a single dose of 1000 milligram (mg) BI 836845 (xentuzumab) as a 1 hour (h) intravenous infusion once a week on Day 1, 8, 15 and 22 in a 28-day course until disease progression, intolerable AEs or other reason necessitating withdrawal. Subjects also received a single oral dose once daily (qd) of 2x 5 mg (10 mg total) tablets of everolimus and 1 tablet of 25 mg exemestane starting 7 days before first administration of BI 836845 (xentuzumab) continously until disease progression, intolerable AEs or other reason necessitating withdrawal.
干预措施: BI 836845 (Drug)
结局指标
主要结局
Progression-free Survival (PFS) - Phase II Part
时间窗: From randomisation until radiological tumour progression according to RECIST 1.1, or death from any cause or data cut-off (25Nov2016), up to 30 months.
Progression-free survival (PFS) in the phase II part is presented. Progression-free survival (PFS) was defined as the time from randomisation until radiological tumour progression according to RECIST 1.1, or death from any cause, whichever occurred earlier. Clinical disease progression was not considered for determination of a PFS event, unless the outcome of the progression was death. The cut-off date was 25th November 2016. At cut-off date, xentuzumab was discontinued in all patients in the experimental arm per sponsor decision, recruitment was also terminated. Patients who discontinued xentuzumab treatment continued with everolimus 10 mg + exemestane 25 mg treatment.
Number of Patients With Dose Limiting Toxicity (DLT) - Phase Ib Part
时间窗: From first administration of study treatment until end of first treatment cycle, up to 28 days.
Number of patients with dose limiting toxicity (DLT) in phase Ib part is presented.
Maximum Tolerated Dose (MTD) - Phase Ib Part
时间窗: up to 28 days.
The Maximum Tolerated Dose (MTD) in this study was defined as the highest dose level examined of trial medication, at which no more than 1 out of 6 patients experienced a DLT during the MTD evaluation period. The MTD evaluation period was defined as the time from the first administration of xentuzumab up to start of cycle 2. A "3+3" Phase Ib dose finding phase was performed to determine the MTD.
次要结局
- Number of Patients With Objective Response (OR) - Phase II Part(From randomisation until the earliest of disease progression, death or last evaluable tumour assessment before start of subsequent anti-cancer therapy or data cut-off (25Nov2016), up to 30 months.)
- Time to Progression (TTP) - Phase II Part(From randomisation until the date of the first objective tumour progression according to RECIST 1.1. or data cut-off (25Nov2016), up to 30 months.)
- Number of Patients With Disease Control (DC) - Phase II Part(From randomisation until data cut-off (25Nov2016), up to 30 months.)
- Time to Objective Response - Phase II Part(From randomisation until first documented complete response (CR) or partial response (PR) or data cut-off (25Nov2016), up to 30 months.)
- Duration of Objective Response - Phase II Part(From randomisation until the earliest of disease progression or death or data cut-off (25Nov2016), up to 30 months.)
- Duration of Disease Control - Phase II Part(From randomisation until the earliest of disease progression or death or data cut-off (25Nov2016), up to 30 months.)