A PHASE I STUDY OF MK-0752 IN PEDIATRIC PATIENTS WITH RECURRENT OR REFRACTORY

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 对于患有复发或难治性中枢神经系统(CNS)恶性肿瘤的儿童，MK-0752将连续口服3天，每7天一次，共28天。起始剂量为200毫克/平方米/天，患者之间的剂量将以设定的增量增加或减少(估计最大剂量为400毫克/平方米/天)。在推荐的MTD，我们将治疗至少6名12岁的可评估患者。虽然剂量的增加将基于在第一个疗程中观察到的毒性，但在第一个疗程之后发生的任何3/4级毒性都将被记录在案，并可能需要审查治疗方案。治疗可持续6个疗程。如果患者正在从治疗中获益，并且在疗程6结束时至少有临床和放射学稳定的疾病，患者可以在研究主席和默克公司的代表事先批准的情况下继续治疗额外的13个疗程(总共19个疗程)。 MK-0752将对患有难治性原发中枢神经系统肿瘤的儿童和青少年具有抗肿瘤活性。 主要目标 目的评估复发或难治性中枢神经系统(CNS)恶性肿瘤患儿应用MK-0752的MTD，并推荐使用MK-0752，连续3天，每7天一次，共28天。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. MK-0752 will be administered orally for 3 consecutive days of every 7 days for 28 days to children with recurrent or refractory central nervous system (CNS) malignancies. The starting dose is 200 mg/m2/day and inter-patient dose escalation or reduction will occur in set increments (to an estimated maximum of 400mg/m2/day). At the recommended MTD, we will treat a minimum of 6 evaluable patients who are < 12 years of age. Although the dose escalation will be based on toxicities observed during the first course, any grade 3/4 toxicities that occur after the first course will be documented and may warrant a review of the treatment regimen. Therapy may continue for 6 courses. If patients are deriving benefit from the therapy and have at least clinical and radiographic stable disease at the end of course 6, patients may continue therapy for an additional 13 courses (for a total of 19 courses) with the prior approval of the study Chair and representatives from Merck and Co. MK-0752 will have anti-tumor activity in children and adolescents with refractory primary CNS tumors. PRIMARY OBJECTIVES To estimate the MTD and recommend a Phase II dose of MK-0752 administered for 3 consecutive days of every 7 days for 28 days to children with recurrent or refractory central nervous system (CNS) malignancies.