A Phase I Study of Ixabepilone in Combination With Epirubicin in Patients With Metastatic Breast Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 42
- 试验地点
- 1
- 主要终点
- Number of Participants With a Dose Limiting Toxicity (DLT)
研究概览
简要总结
Tumor response information was obtained for all participants who received at least 2 cycles of study drug, underwent requisite baseline and on-treatment disease assessments and had at least one post-treatment assessment. Tumor response assessment in evaluable participants was done according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
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
- •Women ≥18 years
- •Histologically or cytologically confirmed diagnosis of metastatic breast cancer
- •Measurable or nonmeasurable disease defined by Response Evaluation Criteria In Solid Tumors (RECIST)
排除标准
- •Number of prior chemotherapy lines of treatment in the metastatic setting ≥2
研究组 & 干预措施
25 mg/m^2 Ixabepilone plus 75 mg/m^2 Epirubicin
Participants received 25 mg/m^2 Ixabepilone as a 3-hour IV infusion following a 3- to 5-minute IV infusion of 75 mg/m^2 epirubicin every 21 days.
干预措施: Ixabepilone (Drug)
25 mg/m^2 Ixabepilone plus 75 mg/m^2 Epirubicin
Participants received 25 mg/m^2 Ixabepilone as a 3-hour IV infusion following a 3- to 5-minute IV infusion of 75 mg/m^2 epirubicin every 21 days.
干预措施: Epirubicin (Drug)
30 mg/m^2 Ixabepilone plus 75 mg/m^2 Epirubicin
Participants received 30 mg/m^2 Ixabepilone as a 3-hour IV infusion following a 3- to 5-minute IV infusion of 75 mg/m^2 epirubicin every 21 days.
干预措施: Ixabepilone (Drug)
30 mg/m^2 Ixabepilone plus 75 mg/m^2 Epirubicin
Participants received 30 mg/m^2 Ixabepilone as a 3-hour IV infusion following a 3- to 5-minute IV infusion of 75 mg/m^2 epirubicin every 21 days.
干预措施: Epirubicin (Drug)
35 mg/m^2 Ixabepilone plus 75 mg/m^2 Epirubicin
Participants received 35 mg/m^2 Ixabepilone as a 3-hour IV infusion following a 3- to 5-minute IV infusion of 75 mg/m^2 epirubicin every 21 days.
干预措施: Ixabepilone (Drug)
35 mg/m^2 Ixabepilone plus 75 mg/m^2 Epirubicin
Participants received 35 mg/m^2 Ixabepilone as a 3-hour IV infusion following a 3- to 5-minute IV infusion of 75 mg/m^2 epirubicin every 21 days.
干预措施: Epirubicin (Drug)
结局指标
主要结局
Number of Participants With a Dose Limiting Toxicity (DLT)
时间窗: From Baseline to the end of Cycle 1 (Day 21)
DLT: any of the following considered related to ixabepilone, epirubicin or combination occurring in Cycle 1: Absolute neutrophil count \<500 cells/mm\^3 for ≥7 consecutive days or febrile neutropenia of any duration;Grade(Gr)4 thrombocytopenia \<25,000 cells/mm\^3 or Gr3 w/bleeding requiring platelet transfusion;Any other drug-related Gr3/4 non-hematologic toxicity except Gr3 injection site reaction, fatigue, transient arthralgia/myalgia;Delayed recovery to Gr≤1 or baseline (except for alopecia) from toxicity related to treatment w/ ixabepilone + epirubicin delaying initiation of next cycle ≥3 wks
Ixabepilone Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (R2PD)
时间窗: Day 21 of Cycle 1
The MTD was the highest dose in which 0/6 or 1/6 participants experienced DLT with at least 2 out of no more than 6 participants experiencing DLT at the next higher dose level. The RP2D was based on the MTD and the assessment of any relevant chronic toxicity. To obtain further confidence in the RP2D, a total maximum of 30 evaluable participants were enrolled at the MTD.
次要结局
- Terminal Half-life (T-Half) of Single-dose Ixabepilone(From the start of the ixabepilone infusion on Day 1 to 120 hours after the first infusion.)
- Epirubicin Cmax(From the start of the ixabepilone infusion on Day 1 to 24 hours after the first infusion.)
- Area Under the Curve, Extrapolated to Infinity (AUC[INF]) of Single-dose Ixabepilone(From the start of the ixabepilone infusion on Day 1 to 120 hours after the first infusion.)
- Epirubicin AUC(INF)(From the start of the ixabepilone infusion on Day 1 to 24 hours after the first infusion.)
- Epirubicin T-Half(From the start of the ixabepilone infusion on Day 1 to 24 hours after the first infusion.)
- Number of Participants With Death, Adverse Events (AEs), Serious Adverse Events (SAEs), Grade 3/4 AEs, or AEs Leading to Discontinuation(Evaluated continuously on study from Baseline to ≤30 days after the last dose of study drug.)
- Maximum Plasma Concentration (Cmax) of Single-dose Ixabepilone(From the start of the ixabepilone infusion on Day 1 to 120 hours after the first infusion.)
- Clearance (CLT) of Single-dose Ixabepilone(From the start of the ixabepilone infusion on Day 1 to 120 hours after the first infusion.)
- Volume of Distribution at Steady State (Vss) of Single-dose Ixabepilone(From the start of the ixabepilone infusion on Day 1 to 120 hours after the first infusion.)
- Epirubicin CLT(From the start of the ixabepilone infusion on Day 1 to 24 hours after the first infusion.)
- Duration of Tumor Response(Time (in months) when criteria for CR or PR are met (which ever occurs first) up to date of progressive disease.)
- Number Of Participants With Tumor Response by Duration of Response Category(Time (in months) when criteria for CR or PR are met (which ever occurs first) up to date of progressive disease.)
- Epirubicin Vss(From the start of the ixabepilone infusion on Day 1 to 24 hours after the first infusion.)
- Number Of Participants With A Best Overall Tumor Response of Complete Response, Partial Response, Stable Disease, And Progressive Disease(From Baseline (up to 2 weeks prior to starting therapy) to the end Cycle 2)