A Randomized, Open-label, Multicenter, Phase 1b/2 Study of Eribulin Mesylate in Combination With PEGylated Recombinant Human Hyaluronidase (PEGPH20) Versus Eribulin Mesylate Alone in Subjects With Human Epidermal Growth Factor Receptor 2 (HER2)-Negative, High-Hyaluronan (HA) Metastatic Breast Cancer (MBC)
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Eisai Inc.
- 入组人数
- 25
- 主要终点
- Phase 1b: Recommended Phase 2 Dose (RP2D) of Eribulin Mesylate in Combination With PEGPH20
研究概览
简要总结
The primary objective for the study is as follows:
For the Phase 1b - to determine safety tolerability and recommended Phase 2 dose (RP2D) of eribulin mesylate in combination with PEGylated recombinant human hyaluronidase (PEGPH20) in participants with Human Epidermal Growth Factor Receptor (HER2)-negative metastatic breast cancer (MBC) previously treated with up to two lines of systemic anticancer therapy in the metastatic setting.
For the Phase 2 - to evaluate objective response rate (ORR) of eribulin mesylate in combination with PEGPH20 in participants with HER2-negative, High-Hyaluronan (HA)-high, MBC previously treated with up to 2 lines of systemic anticancer therapy in the metastatic setting.
详细描述
Phase 1b will occur in two parts:
Part 1: Run-in safety cohort(s) (dose levels 1, 0, and -1, as necessary) of 6 participants each will be conducted until the RP2D is determined. The purpose of the run-in safety cohort(s) is to study the safety of the 2-drug combination and determine a RP2D. Dose limiting toxicity (DLT) will be assessed in the first cycle to determine the RP2D of eribulin mesylate in combination with PEGPH20.
Part 2 (Phase 1b "Expansion Part"): A total of 12 additional participants will be enrolled at the RP2D determined in Part 1 (using Phase 1b criteria, i.e., participants previously treated with up to 2 lines of systemic anticancer therapy) in order to assess the safety profile of the combination and identify any potential safety signals and the incidence of thromboembolic events in this population (RP2D determined dosing).
In Phase 2, participants will be stratified by triple negative breast cancer (TNBC) status and randomized 1:1 to receive eribulin mesylate and PEGPH20 at the established RP2D level or eribulin mesylate alone at 1.4 milligrams per square meters (mg/m^2).
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Eribulin mesylate plus PEGPH20 (Phase 1b)
Recommended Phase 2 dose (RP2D) will be determined from the below dose levels:
- Dose level 1: PEGPH20 (3.0 microgram per kilogram (mcg/kg)) followed by eribulin mesylate (1.4 milligrams per square meter (mg/m^2)) or
- Dose level 0: PEGPH20 (1.6 mcg/kg) followed by eribulin mesylate (1.4 mg/m^2) or
- Dose level -1: PEGPH20 (1.6 mcg/kg) followed by eribulin mesylate (1.1 mg/m^2)
Dose level 1 can be selected as the RP2D if no more than 1 out of 6 participants has a DLT; DLT was only observed from the first treatment cycle; otherwise, Dose level 0 will be assessed in a second cohort of 6 subjects and will be selected as the RP2D if no more than 1 subject has a DLT. Otherwise, Dose level - 1 will be assessed in a third cohort of 6 subjects. Upon determination of the RP2D, study Phase 1b Expansion Part will proceed to confirm the RP2D, and thereafter Phase 2 part will proceed.
干预措施: Eribulin mesylate (Drug)
Eribulin mesylate plus PEGPH20 (Phase 2)
Participants will receive eribulin mesylate and PEGPH20 at the established RP2D level achieved in the Phase 1b.
干预措施: Eribulin mesylate (Drug)
Eribulin mesylate (Phase 2)
Participants will receive eribulin mesylate at 1.4 mg/m^2.
干预措施: Eribulin mesylate (Drug)
结局指标
主要结局
Phase 1b: Recommended Phase 2 Dose (RP2D) of Eribulin Mesylate in Combination With PEGPH20
时间窗: Up to Cycle 28 (Cycle Length= 21 days)
The RP2D was the maximum tolerated dose (MTD) or less. The MTD was determined as the dose level (1, 0) at which less than or equal to (\<=) 1 of 6 evaluable participants experienced dose limiting toxicity (DLT) within the first 21 days of treatment (end of Cycle 1). Upon determination of RP2D in Cycle 1 of Phase 1b, RP2D was to be confirmed in Phase 1b-expansion Part.
Phase 1b: Recommended Phase 2 Dose (RP2D) of PEGPH20 in Combination With Eribulin Mesylate
时间窗: Up to Cycle 28 (Cycle Length= 21 days)
The RP2D was the MTD or less. The MTD was determined as the dose level (1, 0) at which \<=1 of 6 evaluable participants experienced DLT within the first 21 days of treatment (end of Cycle 1). Upon determination of RP2D in Cycle 1 of Phase 1b, RP2D was to be confirmed in Phase 1b-expansion Part.
次要结局
未报告次要终点