A Phase 1 Study of Eribulin Mesylate, a Novel Microtubule Targeting Chemotherapeutic Agent in Children With Refractory or Recurrent Solid Tumors (Excluding CNS), Including Lymphomas
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Eisai Inc.
- 入组人数
- 23
- 试验地点
- 18
- 主要终点
- Number of Participants With Clinically Significant Electrocardiogram (EKG)
研究概览
简要总结
This is a Phase 1 study of eribulin mesylate in pediatric participants with recurrent or refractory solid tumors (excluding CNS), including lymphomas. Eribulin mesylate will be administered intravenously, once per day on Days 1 and 8 of a 21-day cycle. This study aims to determine the maximum tolerated dose (MTD) and/or the Recommended Phase 2 Dose (RP2D) of this regimen in Part A1 (participants greater than or equal to [>=] 12 months and less than [<] 18 years). Part A2 will enroll infants (greater than [>] 6 months and <12 months) one dose level behind the dose level at which participants in Part A1 are enrolling, in order to maximize safety for infant participants. Additionally, this study aims to describe the toxicities and the pharmacokinetics of eribulin mesylate when administered to children. In a preliminary manner, the antitumor effect of eribulin mesylate will also be described.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 6 Months 至 17 Years（Child）
- 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
Eribulin mesylate will be administered intravenously on Days 1 and 8 of each 21-day cycle. A cycle of therapy is considered to be 21 days. The starting dose for eribulin mesylate will be at 1.1 milligram per square meter (mg/m^2) (Dose Level 1), which is approximately 80% of the adult MTD, and will be escalated up to no more than 2.2 mg/m^2.
干预措施: Eribulin Mesylate (Drug)
结局指标
主要结局
Number of Participants With Clinically Significant Electrocardiogram (EKG)
时间窗: First dose of study drug (Baseline) up to 30 days after last dose of study drug (Cycle 8 Day 38)
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
时间窗: First dose of study drug (Baseline) up to 30 days after last dose of study drug (Cycle 8 Day 38)
TEAEs were defined as those adverse events (AEs) that occurred (or worsened, if present at Baseline) after the first dose of study drug through 30 days after the last dose of study drug. An AE was defined as any untoward medical occurrence in a participants or clinical investigation participant administered an investigational product. An AE does not necessarily have a causal relationship with medicinal product. A SAE was defined as any AE if it resulted in death or life-threatening AE or required inpatient hospitalization or prolongation of existing hospitalization or resulted in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions or was a congenital anomaly/birth defect.
T1/2: Terminal Half-life for Eribulin Mesylate
时间窗: Day 1 predose and at 10, 30 minutes, 1, 2, 4, 6, 24, 48, 72, 96 or 120 hours post-dose
Maximum Tolerated Dose (MTD) of Eribulin Mesylate
时间窗: First dose of study drug (Baseline) up to Cycle 1 Day 21
MTD: maximum dose at which \<one third participants had DLT in Cycle 1. DLT: Grade 3/4 drug-related non hematological toxicity (except Grade 3 nausea, vomiting of \<3 days, Grade 3 liver enzyme elevation with alanine transaminase/aspartate transaminase and gamma glutamyl transferase that returned to Grade \<=1 or baseline prior to next dose; Grade 3 fever, infection, hypophosphatemia, hypokalemia, hypocalcemia/hypomagnesemia responsive to oral supplementation). Non-hematological toxicity causing \>=14 days delay between treatment cycles. Haematological DLTs included: Grade 4 neutropenia/platelets\<75,000/mm\^3 on Day 8 that does not resolve to absolute neutrophil count \>=750/mm\^3 and platelets\>=75,000/mm\^3 by Day 11, neutropenia for \>7 days; platelet count \<25,000/mm\^3, or required platelet transfusion, on 2 separate days within 7-day period;Grade 3 thrombocytopenia complicated by bleeding and/or required platelet transfusion;myelosuppression causing \>14 days delay between treatment cycles.
Number of Participants With Clinically Significant Change From Baseline in Clinical Laboratory Values
时间窗: First dose of study drug (Baseline) up to 30 days after last dose of study drug (Cycle 8 Day 38)
Number of Participants With Clinically Significant Vital Sign Values
时间窗: First dose of study drug (Baseline) up to 30 days after last dose of study drug (Cycle 8 Day 38)
Cmax: Maximum Observed Plasma Concentration for Eribulin Mesylate
时间窗: Day 1 predose and at 10, 30 minutes, 1, 2, 4, 6, 24, 48, 72, 96 or 120 hours post-dose
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Eribulin Mesylate
时间窗: Day 1 predose and at 10, 30 minutes, 1, 2, 4, 6, 24, 48, 72, 96 or 120 hours post-dose
AUC 0-t: Area Under the Concentration-time Curve From Zero (Pre-dose) to Time of Last Quantifiable Concentration for Eribulin Mesylate
时间窗: Day 1 predose and at 10, 30 minutes, 1, 2, 4, 6, 24, 48, 72, 96 or 120 hours post-dose
AUC 0-inf: Area Under the Concentration-time Curve From Zero (Pre-dose) Extrapolated to Infinite Time for Eribulin Mesylate
时间窗: Day 1 predose and at 10, 30 minutes, 1, 2, 4, 6, 24, 48, 72, 96 or 120 hours post-dose
CL: Clearance for Eribulin Mesylate
时间窗: Day 1 predose and at 10, 30 minutes, 1, 2, 4, 6, 24, 48, 72, 96 or 120 hours post-dose
Vd: Volume of Distribution for Eribulin Mesylate
时间窗: Day 1 predose and at 10, 30 minutes, 1, 2, 4, 6, 24, 48, 72, 96 or 120 hours post-dose
次要结局
- Number of Participants With Best Overall Response(First dose of study drug (Baseline) up to approximately Cycle 8 (21-days treatment cycle))