Phase I-II Study of MEK 162 for Children With Low-Grade Gliomas and Other Ras/Raf/ERK Pathway Activated Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 105
- 试验地点
- 15
- 主要终点
- Best Overall Response Rate (Strata 1 and 2)
研究概览
简要总结
The goal of this clinical trial is to study the drug MEK162 in children with a brain tumor call low-grade glioma, as well as in children with other tumors in which a specific growth signal is abnormally turned on. The main questions it aims to answer are:
What is the correct dose of MEK162 in children? What are the side effects of MEK162 in children? Is MEK162 effective in children with low-grade glioma?
Participants on the study receive MEK162 by mouth twice daily for up to 2 years.
详细描述
PROTOCOL SUMMARY:
Phase 1: Patients with non-hematologic malignancies that are recurrent, progressive, or refractory after standard up-front therapy receiving MEK162 will define the maximum tolerated dose (MTD), dose-limiting toxicities (DLT), and toxicity profile.
Phase 2: Patients with recurrent or progressive tumors signaling through the ras/raf pathway after standard up-front therapy will be treated in three strata to define the activity of MEK162.
Stratum 1: Pediatric patients with recurrent or progressive low-grade glioma (LGG) characterized by a BRAF truncated fusion (KIAA1549 and similar translocations).
Stratum 2: Pediatric patients with neurofibromatosis type 1 (NF1) and recurrent or progressive LGG.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
Phase 1
Patients with non-hematologic malignancies that are recurrent, progressive, or refractory after standard up-front therapy receiving MEK162 will define the MTD, DLT, and toxicity profile.
干预措施: MEK162 (Drug)
Phase 2
Children with recurrent tumors signaling through the Ras/Raf pathway will be treated in 3 strata to define the activity of MEK162. S1: Children with LGG characterized by a BRAF truncated fusion (KIAA1549 and similar translocations). S2: Children with NF1 and LGG. S 3: Children with tumors involving the Ras/Raf pathway not included in strata 1 or 2.
干预措施: MEK162 (Drug)
Target Validation
Patients eligible for phase 2 (any stratum) for whom tumor biopsy or resection is clinically indicated may be enrolled on the target validation arm. Patients will receive MEK162 for 7 to 21 days prior to their surgery. Tumor sample will be analyzed for drug concentration and target inhibition.
干预措施: MEK162 (Drug)
结局指标
主要结局
Best Overall Response Rate (Strata 1 and 2)
时间窗: 48 weeks
For each stratum, the percentage of patients achieving at least a minor response (defined as greater than or equal to 25% decrease in maximal two dimensional measurements compared to baseline) during the first 12 cycles (nominally 48 weeks) of treatment will be reported.
12 Cycle Progression-free and Overall Survival (Strata 1 and 2)
时间窗: 48 weeks
Progression free and overall survival will be reported as Kaplan-Meier estimate who are alive without disease progression, alive with disease progression, deceased without disease progression, and deceased with disease progression 12 cycles (48 weeks) after treatment initiation.
次要结局
未报告次要终点
研究者
Nathan Robison, M.D.
Medical Director of Inpatient Services, Attending Neuro-Oncologist, Associate Professor
Children's Hospital Los Angeles