Hydroxychloroquine (HCQ) in Combination With Abemaciclib and Endocrine Therapy in HR+/Her 2- Advanced Breast Cancer After a Lead in Dose Escalation Cohort of HCQ and Abemaciclib in Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Dose-limiting toxicities during dose-escalation phase.
研究概览
简要总结
The hypothesis is that abemaciclib synergizes with autophagy inhibitor hydroxychloroquine (HCQ/ Plaquenil), inducing apoptosis leading to tumor regression.
详细描述
Part 1: 3+3 dose escalation of HCQ combined with abemaciclib in advanced solid tumors.
Part 2: HCQ at top-dose level from part one is combined with abemaciclib and endocrine therapy in HR+/Her 2- advanced breast cancer (ABC) and divided into two cohorts based on prior exposure to endocrine therapy.
Primary Objective
- Dose-escalation cohort: To determine safety and tolerability of HCQ combined with abemaciclib.
- Dose-expansion cohort: To determine safety and tolerability of HCQ combined with abemaciclib and endocrine therapy in HR+/Her2- ABC.
Secondary Objectives
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Abemaciclib and HCQ 200 mg b.i.d.
HCQ will have a dose escalation of a 3 + 3 design.
干预措施: Abemaciclib (Drug)
Abemaciclib and HCQ 200 mg b.i.d.
HCQ will have a dose escalation of a 3 + 3 design.
干预措施: Hydroxychloroquine 200 mg (Drug)
Abemaciclib and HCQ 400 mg b.i.d.
HCQ will have a dose escalation of a 3 + 3 design.
干预措施: Abemaciclib (Drug)
Abemaciclib and HCQ 400 mg b.i.d.
HCQ will have a dose escalation of a 3 + 3 design.
干预措施: Hydroxychloroquine 400 mg (Drug)
Abemaciclib and HCQ 600 mg b.i.d.
HCQ will have a dose escalation of a 3 + 3 design.
干预措施: Abemaciclib (Drug)
Abemaciclib and HCQ 600 mg b.i.d.
HCQ will have a dose escalation of a 3 + 3 design.
干预措施: Hydroxychloroquine 600 mg (Drug)
Abemaciclib + HCQ (Optimal Dose) + endocrine therapy
This group will be divided into two cohorts:
- eligible participants who are endocrine therapy naive.
- eligible participants who had one prior line of endocrine therapy.
干预措施: Abemaciclib (Drug)
Abemaciclib + HCQ (Optimal Dose) + endocrine therapy
This group will be divided into two cohorts:
- eligible participants who are endocrine therapy naive.
- eligible participants who had one prior line of endocrine therapy.
干预措施: Hydroxychloroquine 200 mg (Drug)
Abemaciclib + HCQ (Optimal Dose) + endocrine therapy
This group will be divided into two cohorts:
- eligible participants who are endocrine therapy naive.
- eligible participants who had one prior line of endocrine therapy.
干预措施: Faslodex (Drug)
Abemaciclib + HCQ (Optimal Dose) + endocrine therapy
This group will be divided into two cohorts:
- eligible participants who are endocrine therapy naive.
- eligible participants who had one prior line of endocrine therapy.
干预措施: Anastrazole (Drug)
Abemaciclib + HCQ (Optimal Dose) + endocrine therapy
This group will be divided into two cohorts:
- eligible participants who are endocrine therapy naive.
- eligible participants who had one prior line of endocrine therapy.
干预措施: Letrozole (Drug)
Abemaciclib + HCQ (Optimal Dose) + endocrine therapy
This group will be divided into two cohorts:
- eligible participants who are endocrine therapy naive.
- eligible participants who had one prior line of endocrine therapy.
干预措施: Hydroxychloroquine 400 mg (Drug)
Abemaciclib + HCQ (Optimal Dose) + endocrine therapy
This group will be divided into two cohorts:
- eligible participants who are endocrine therapy naive.
- eligible participants who had one prior line of endocrine therapy.
干预措施: Hydroxychloroquine 600 mg (Drug)
结局指标
主要结局
Dose-limiting toxicities during dose-escalation phase.
时间窗: 28 days for each cohort
The number of participants with dose-limiting toxicities during the dose-escalation phase (HCQ in combination with abemaciclib).
Dose-limiting toxicities in dose-expansion phase.
时间窗: 28 days for each cohort
The number of participants with dose-limiting toxicities during the dose-expansion phase (maximum-tolerated dose of HCQ and abemaciclib in combination with endocrine therapy.
次要结局
- Progression-free survival.(1 Year)
- Overall response rate.(1 Year)
研究者
Smitha Menon
Associate Professor
Medical College of Wisconsin