A Multi-center Phase I Trial of Temsirolimus in Combination With Valproic Acid in Children and Adolescents With Multiply Relapsed Pediatric Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 7
- 试验地点
- 2
- 主要终点
- Maximum tolerated dose (MTD) of temsirolimus in combination with valproic acid
研究概览
简要总结
RATIONALE: Drugs such as temsirolimus and valproic acid may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Valproic acid may also stop the growth of solid tumors by blocking blood flow to the tumor.
PURPOSE: This phase I trial is studying the side effects and the best dose of temsirolimus when given together with valproic acid in treating young patients with relapsed neuroblastoma, bone sarcoma, or soft tissue sarcoma.
详细描述
OBJECTIVES:
Primary
- To identify the maximum-tolerated dose of temsirolimus in combination with valproic acid in highly pretreated pediatric patients with refractory solid tumors.
Secondary
- To estimate the objective response rate in patients treated with this regimen.
- To estimate the progression-free survival of patients treated with this regimen.
- To explore the association between tumor IGF-IR, mTOR expression, HDAC, autophagy biomarkers, and sera levels of temsirolimus, valproate, and VEGF-A with toxicity and disease response.
- To evaluate the ability of selected member divisions of a newly developed North Carolina-based pediatric oncology consortium to cooperate in clinical trials.
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
- 2 Years 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
Single Arm Temsirolimus + Valproic Acid
Drug: temsirolimus 60-230mg/m2 weekly during each 28 day course, for up to 12 courses
Drug: valproic acid (VPA) All patients will be given oral VPA (5 mg/kg, 3 times a day for each 28 day course, up to 12 courses
干预措施: Temsirolimus (Drug)
Single Arm Temsirolimus + Valproic Acid
Drug: temsirolimus 60-230mg/m2 weekly during each 28 day course, for up to 12 courses
Drug: valproic acid (VPA) All patients will be given oral VPA (5 mg/kg, 3 times a day for each 28 day course, up to 12 courses
干预措施: Valproic Acid (Drug)
结局指标
主要结局
Maximum tolerated dose (MTD) of temsirolimus in combination with valproic acid
时间窗: 4 weeks
The planned starting dose of Temsirolimus is 60mg/M2. The traditional 3+3 design will be used, where the MTD is defined as the dose with the probability of a DLT of 0.20
次要结局
- Objective response rate(every 12 weeks)
- Progression-free survival(3 years)
- Temsirolimus pharmakokinetic parameters (Maximum plasma concentration)(doses 1 and 5)