ADVL0419: APHASE 1 STUDY OF VALPROIC ACID IN CHILDREN WITH RECURRENT/PROGRESSIV

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。这项研究的主要目的是确定和描述口服丙戊酸(VPA)每天两次的剂量，以维持儿童复发或难治性实体肿瘤(包括中枢神经系统肿瘤)的血药浓度在100-150微克/毫升或150-200微克/毫升。第二个目标是：1)在目标总谷浓度下测量血清VPA谷浓度的稳态。2)评价儿童每日两次给药的药动学特征。3)评价VPA靶向浓度下外周血单核细胞的稳态组蛋白乙酰化状态。4)研究组蛋白乙酰化与VPA谷底游离或总浓度之间的关系。5)在1期试验范围内初步确定VPA的抗肿瘤活性。

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. The primary aim of this study is to define and describe the toxicities of oral valproic acid (VPA) administered twice daily at doses required to maintain serum trough concentrations of 100-150 mcg/ml or 150-200 mcg/ml in children with recurrent or refractory solid tumors, including CNS tumors. The secondary aims are: 1) To measure the steady state of serum trough concentration of free VPA at targeted total trough VPA concentraion. 2) To evaluate the pharmacokinetic profile of twice daily VPA administration in children. 3) To evaluate the steady state histone acetylation status of peripheral blood monocytes at the targeted trough VPA concentrations. 4) To investigate potential correlations between histone acetylation and free or total VPA trough concentrations. 5) To preliminary define the antitumor activity of VPA within the confines of a Phase 1 trial.