A Phase 1b/2, Multicenter, Open-Label, Dose-Escalation and Confirmation Study of Eribulin in Combination With Capecitabine
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 76
- 主要终点
- Phase 1b: Number of Participants With Dose-limiting Toxicities (DLTs) as Per National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (NCI CTCAE v3.0)
研究概览
简要总结
This is a Phase 1b/2, multi-center, open-label, dose escalation (in 2 different dosing schedules [1 and 2]) and dose-confirmation study of eribulin administered in combination with capecitabine.
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
Dose-escalation Phase (Phase 1b)
Participants with advanced and/or metastatic tumors will receive eribulin mesylate as a 2 to 5 min Intravenous (IV) bolus or infusion in two different schedules (Schedule 1 [1.2, 1.6, 2.0 mg/m2], given on Day 1 only, and Schedule 2 [0.7, 1.1, 1.7 mg/m^2], given on Days 1 and 8) and oral capecitabine 1000 mg/m2 bid on Days 1-14 (21-day cycles) in both schedules. If maximum tolerated dose (MTD) is not observed at dose level 3 the dose of capecitabine might be escalated to 1250 mg/m^2 bid on Days 1-14 (21-day cycles) depending on the Dose limiting toxicities (DLTs) observed and/or pharmacokinetic (PK) data when available. Based on the data and safety monitoring board review of dose escalation phase data (DLTs that will be observed in first cycle), Dose-Confirmation Phase (Phase 2) will may get initiated.
干预措施: Eribulin mesylate (Drug)
Dose-escalation Phase (Phase 1b)
Participants with advanced and/or metastatic tumors will receive eribulin mesylate as a 2 to 5 min Intravenous (IV) bolus or infusion in two different schedules (Schedule 1 [1.2, 1.6, 2.0 mg/m2], given on Day 1 only, and Schedule 2 [0.7, 1.1, 1.7 mg/m^2], given on Days 1 and 8) and oral capecitabine 1000 mg/m2 bid on Days 1-14 (21-day cycles) in both schedules. If maximum tolerated dose (MTD) is not observed at dose level 3 the dose of capecitabine might be escalated to 1250 mg/m^2 bid on Days 1-14 (21-day cycles) depending on the Dose limiting toxicities (DLTs) observed and/or pharmacokinetic (PK) data when available. Based on the data and safety monitoring board review of dose escalation phase data (DLTs that will be observed in first cycle), Dose-Confirmation Phase (Phase 2) will may get initiated.
干预措施: Capecitabine (Drug)
Dose-confirmation Phase (Phase 2)
Participants with advanced and/or metastatic tumors will receive Eribulin mesylate at the MTD for the selected schedule of dose escalation phase based on safety/PK data.
干预措施: Eribulin mesylate (Drug)
Dose-confirmation Phase (Phase 2)
Participants with advanced and/or metastatic tumors will receive Eribulin mesylate at the MTD for the selected schedule of dose escalation phase based on safety/PK data.
干预措施: Capecitabine (Drug)
结局指标
主要结局
Phase 1b: Number of Participants With Dose-limiting Toxicities (DLTs) as Per National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (NCI CTCAE v3.0)
时间窗: Cycle 1 (21 days)
DLTs as per NCI CTCAE v3.0 were defined as:1) Neutropenia Grade 4 that lasted at least 7 days, 2) Neutropenia Grade 3 or 4 complicated by fever and/or infection (absolute neutrophil count \[ANC\] less than 1.0\*10\^9/liter \[L\], fever of at least 38.5 degree celsius \[°C\]), 3)Thrombocytopenia Grade 4, 4) Thrombocytopenia Grade 3 complicated by bleeding and/or requiring platelet or blood transfusion, 5) Non-hematological toxicity Grade 3 or higher (excluding Grade 3 nausea, and Grade 3 or 4 vomiting or diarrhea in participants who had not received optimal treatment with antiemetic and/or antidiarrheal medication; excluding laboratory abnormalities without clinical symptoms), 6) Delayed recovery from treatment-related toxicity resulting in dose delay greater than 14 days, 7) Failure to administer at least 75 percent (%) of planned study drugs during Cycle 1 as result of Grade 2 or higher treatment-related toxicity that constituted increase of at least 2 grades from baseline.
Phase 2: Objective Response Rate (ORR)
时间窗: From the first dose of study drug until PD or up to 30 days after the last dose of study treatment (up to approximately 3.75 years)
ORR was defined as the percentage of participants who had either a confirmed complete response (CR) or partial response (PR). ORR was assessed based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v 1.1). CR was defined as disappearance of all target lesions. All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis to less than (\<) 10 millimeter (mm). PR was defined as at least a 30 percent (%) decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of the longest diameter. ORR was summarized using the Clopper-Pearson method.
次要结局
- Phase 2: Duration of Stable Disease (SD)(From the first dose of study drug until PD or 30 days after the last dose of study treatment (up to approximately 3.75 years))
- Phase 2: Progression-free Survival (PFS)(From the first dose of study drug until PD or death due to any cause or 30 days after the last dose of study treatment (up to approximately 3.75 years))
- Phase 1b and Phase 2: Percentage of Participants With Non-CR/Non-PD(From the first dose of study drug until PD or up to 30 days after the last dose of study treatment (up to approximately 3.75 years))
- Phase 2: Time to Response(From the first dose of study drug treatment start date until date of first documented evidence of CR or PR or up to 30 days after the last dose of study treatment (up to approximately 3.75 years))
- Phase 2: Stable Disease (SD) Rate(From the first dose of study drug until PD or up to 30 days after the last dose of study treatment (up to approximately 3.75 years))
- Phase 2: Duration of Response (DOR)(From date of the first CR or PR until the date of first documentation of PD or death or up to 30 days after the last dose of study treatment (up to approximately 3.75 years))
- Phase 2: Disease Control Rate (DCR)(From the first dose of study drug until PD or 30 days after the last dose of study treatment (up to approximately 3.75 years))
- Phase 2: Clinical Benefit Rate (CBR)(From the first dose of study drug until PD or 30 days after the last dose of study treatment (up to approximately 3.75 years))