Phase I/II Open Label, Dose Escalation Trial to Determine the MTD, Safety, PK and Efficacy of Afatinib Monotherapy in Children Aged ≥1 Year to <18 Years With Recurrent/Refractory Neuroectodermal Tumours, Rhabdomyosarcoma and/or Other Solid Tumours With Known ErbB Pathway Deregulation Regardless of Tumour Histology
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 56
- 试验地点
- 28
- 主要终点
- Number of Participants With Objective Response - Maximum Tolerated Dose Expansion (MTD) Cohort
研究概览
简要总结
Open-label, dose escalation, monotherapy, basket trial with biomarker specific MTD expansion cohort/Phase II part.
The trial will consist of 2 parts:
- Dose finding part to determine the MTD
- Biomarker specific MTD expansion cohort/Phase II part to assess clinical anti-tumour activity in included tumour types
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
- 1 Year 至 18 Years（Child, 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
afatinib
dose escalation
干预措施: afatinib (Drug)
结局指标
主要结局
Number of Participants With Objective Response - Maximum Tolerated Dose Expansion (MTD) Cohort
时间窗: Assessed every 8 weeks until progression of disease, up to 336 days.
Number of participants with objective response for maximum tolerated dose expansion (MTD) cohort was reported. The objective response was defined as a best overall response of complete response or partial response based on investigator's assessment according to the institutional response evaluation criteria for the given tumour type, assessed every 8 weeks until progression.
Number of Participants With Dose Limiting Toxicity Adverse Events - Dose Finding Part
时间窗: During the first course (28 days) of treatment.
Number of participants with Dose Limiting Toxicity adverse events for Dose finding part was reported.
Area Under the Curve Over Dosing Interval τ at Steady State (AUCτ,ss) - Dose Finding Part
时间窗: Pre-dose before afatinib administration then 1 hour (h), 2 h, 3 h, 4 h, 5 h, 6 h, 8 h and 24 h after administration at steady state on Day 8.
Area under the curve over dosing interval τ at steady state (AUCτ,ss) for Dose finding part was reported.
Maximum Measured Concentration of the Analyte in Plasma at Steady State (Cmax,ss) - Dose Finding Part
时间窗: Pre-dose before afatinib administration then 1 hour (h), 2 h, 3 h, 4 h, 5 h, 6 h, 8 h and 24 h after administration at steady state on Day 8.
Maximum measured concentration of the analyte in plasma at steady state (Cmax,ss) for Dose finding part was reported.
次要结局
- Time From (Last) Dosing to the Maximum Measured Concentration at Steady State (Tmax,ss) - Dose Finding Part/Maximum Tolerated Dose (MTD) Expansion Cohort(Pre-dose before afatinib administration then 1 hour (h), 2 h, 3 h, 4 h, 5 h, 6 h, 8 h and 24 h after administration at steady state on Day 8.)
- Accumulation (or Effective) Half-life - Dose Finding Part/Maximum Tolerated Dose (MTD) Expansion Cohort(Pre-dose before afatinib administration then 1 hour (h), 2 h, 3 h, 4 h, 5 h, 6 h, 8 h and 24 h after administration at steady state on Day 8.)
- Progression Free Survival - Maximum Tolerated Dose (MTD) Expansion Cohort(From the first treatment until date of first progression or death, up to 336 days.)
- Maximum Measured Concentration (Cmax) - Dose Finding Part/Maximum Tolerated Dose (MTD) Expansion Cohort(Pre-dose before afatinib administration then 1 hour (h), 2 h, 3 h, 4 h, 5 h, 6 h, 8 h and 24 h after administration on Day 1.)
- Maximum Measured Concentration of the Analyte in Plasma at Steady State (Cmax,ss) - Maximum Tolerated Dose (MTD) Expansion Cohort(Pre-dose before afatinib administration then 1 hour (h), 2 h, 3 h, 4 h, 5 h, 6 h, 8 h and 24 h after administration at steady state on Day 8.)
- Number of Participants With Objective Response - Dose Finding Part(Assessed every 8 weeks until progression of disease, up to 336 days.)
- Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to 24 Hours (AUC0-24) - Dose Finding Part(Pre-dose before afatinib administration then 1 hour (h), 2 h, 3 h, 4 h, 5 h, 6 h, 8 h and 24 h after administration on Day 1.)
- Duration of Objective Response - Maximum Tolerated Dose (MTD) Expansion Cohort(From first documented response until the earliest of disease progression or death, up to 336 days.)
- Time From (Last) Dosing to the Maximum Measured Concentration (Tmax) - Dose Finding Part/Maximum Tolerated Dose (MTD) Expansion Cohort(Pre-dose before afatinib administration then 1 hour (h), 2 h, 3 h, 4 h, 5 h, 6 h, 8 h and 24 h after administration on Day 1.)
- Area Under the Curve Over Dosing Interval τ at Steady State (AUCτ,ss) - Maximum Tolerated Dose (MTD) Expansion Cohort(Pre-dose before afatinib administration then 1 hour (h), 2 h, 3 h, 4 h, 5 h, 6 h, 8 h and 24 h after administration at steady state on Day 8.)