Fulvestrant Alone Versus Fulvestrant and Everolimus Versus Fulvestrant, Everolimus and Anastrozole: A Phase III Randomized Placebo-Controlled Trial in Postmenopausal Patients
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 37
- 试验地点
- 223
- 主要终点
- Progression-Free Survival (Fulvestrant vs Fulvestrant + Everolimus )
研究概览
简要总结
This randomized Phase III trial studies how well the combination of fulvestrant and everolimus together or the combination of anastrozole, fulvestrant and everolimus together, improve progression-free survival (PFS) versus fulvestrant alone.
详细描述
OBJECTIVES:
Primary
- To test the benefit of interfering with the function of the estrogen receptor (ER) and providing downstream target inhibition (PI3K/AKT/mTOR) with a combination of optimal dose fulvestrant and everolimus (Arm 2) to improve progression-free survival compared to the optimal dose fulvestrant alone (Arm 1).
- To test the benefit of adding the non-steroidal aromatase inhibitor anastrozole to optimal dose fulvestrant and everolimus (Arm 3) in order to improve progression free survival over optimal dose fulvestrant (Arm 1).
Secondary
- To compare progression-free survival among those receiving fulvestrant + everolimus + anastrozole (Arm 3) versus fulvestrant + everolimus (Arm 2).
- To compare overall survival among the treatment arms in post-menopausal patients with hormone-receptor positive (HR+) Stage IV breast cancer.
- To assess and compare toxicities, feasibility and compliance among the study regimens.
- To compare response rates and clinical benefit rates among the study regimens.
- To test molecular determinants of response to endocrine therapy and everolimus in circulating tumor cells:
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（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
Arm 1: fulvestrant + everolimus placebo + anastrozole placebo
Patients receive an injection of fulvestrant in each buttock on Days 1 &15 for Cycle 1 and then Day 1 only for subsequent cycles. Patients also receive an oral placebo daily for both everolimus and anastrozole. This treatment regimen will continue until disease progression or toxicity.
干预措施: Fulvestrant (Drug)
Arm 1: fulvestrant + everolimus placebo + anastrozole placebo
Patients receive an injection of fulvestrant in each buttock on Days 1 &15 for Cycle 1 and then Day 1 only for subsequent cycles. Patients also receive an oral placebo daily for both everolimus and anastrozole. This treatment regimen will continue until disease progression or toxicity.
干预措施: Placebo - Anastrozole (Drug)
Arm 1: fulvestrant + everolimus placebo + anastrozole placebo
Patients receive an injection of fulvestrant in each buttock on Days 1 &15 for Cycle 1 and then Day 1 only for subsequent cycles. Patients also receive an oral placebo daily for both everolimus and anastrozole. This treatment regimen will continue until disease progression or toxicity.
干预措施: Placebo - Everolimus (Drug)
Arm 2: fulvestrant + everolimus + anastrozole placebo
Patients receive an injection of fulvestrant in each buttock on Days 1 &15 for Cycle 1 and then Day 1 only for subsequent cycles. Patients also receive an oral everolimus and an oral placebo for anastrozole daily. This treatment regimen will continue until disease progression or toxicity.
干预措施: Fulvestrant (Drug)
Arm 2: fulvestrant + everolimus + anastrozole placebo
Patients receive an injection of fulvestrant in each buttock on Days 1 &15 for Cycle 1 and then Day 1 only for subsequent cycles. Patients also receive an oral everolimus and an oral placebo for anastrozole daily. This treatment regimen will continue until disease progression or toxicity.
干预措施: Everolimus (Drug)
Arm 2: fulvestrant + everolimus + anastrozole placebo
Patients receive an injection of fulvestrant in each buttock on Days 1 &15 for Cycle 1 and then Day 1 only for subsequent cycles. Patients also receive an oral everolimus and an oral placebo for anastrozole daily. This treatment regimen will continue until disease progression or toxicity.
干预措施: Placebo - Anastrozole (Drug)
Arm 3: fulvestrant + everolimus + anastrozole
Patients receive an injection of fulvestrant in each buttock on Days 1 &15 for Cycle 1 and then Day 1 only for subsequent cycles. Patients also receive everolimus and anastrozole by mouth daily. This treatment regimen will continue until disease progression or toxicity.
干预措施: Fulvestrant (Drug)
Arm 3: fulvestrant + everolimus + anastrozole
Patients receive an injection of fulvestrant in each buttock on Days 1 &15 for Cycle 1 and then Day 1 only for subsequent cycles. Patients also receive everolimus and anastrozole by mouth daily. This treatment regimen will continue until disease progression or toxicity.
干预措施: Anastrozole (Drug)
Arm 3: fulvestrant + everolimus + anastrozole
Patients receive an injection of fulvestrant in each buttock on Days 1 &15 for Cycle 1 and then Day 1 only for subsequent cycles. Patients also receive everolimus and anastrozole by mouth daily. This treatment regimen will continue until disease progression or toxicity.
干预措施: Everolimus (Drug)
结局指标
主要结局
Progression-Free Survival (Fulvestrant vs Fulvestrant + Everolimus )
时间窗: up to 5 years
From date of registration to date of first documentation of progression or death due to any cause. Participants last known to be alive are censored at date of last contact.
Progression-free Survival (Fulvestrant Versus Fulvestrant + Everolimus + Anastrozole)
时间窗: up to 5 years
From date of registration to date of first documentation of progression or death due to any cause. Participants last known to be alive without report of progression are censored at date of last contact.
次要结局
- Progression Free Survival (Fulvestrant + Everolimus vs Fulvestrant + Everolimus + Anastrozole)(up to 5 years)
- Overall Survival(up to 5 years)
- Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs(Duration of treatment and follow up until death or 5 years post registration)
- Response Rate(assessed every 12 weeks, up to 5 years)
- Clinical Benefit Rate(assessed every 12 weeks, up to 5 years)
- Molecular Determinants of Response in Circulating Tumor Cells: CTC-ETI(Day 1, Day 29, time of progression (Day 29 to be collected only if Day 1 CTC was elevated.))