CLINICAL TRIAL: ADVL0419, A PHASE I STUDY OF VALPROIC ACID IN CHILDREN WITH RECU

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 假设 组蛋白去乙酰化酶抑制剂（HDAC）在多种儿童肿瘤中具有抗肿瘤活性。 具体目标 主要目的：定义和描述复发性或难治性实体瘤（包括CNS肿瘤）儿童中丙戊酸（VPA）口服给药（每日两次，剂量为维持血清谷浓度100-150 mcg/ml或150-200 mcg/ml）的毒性。 次要目的：测定目标总VPA谷浓度下游离VPA的稳态血清谷浓度。 评价儿童VPA每日两次给药的药代动力学特征。 评价目标VPA谷浓度下外周血单核细胞的稳态组蛋白乙酰化状态。 研究组蛋白乙酰化与游离或总VPA谷浓度之间的潜在相关性。 在I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. HYPOTHESIS Histone deacytelase inhibitors (HDAC) will have antitumor activity in a variety of childhood tumors. SPECIFIC AIMS Primary Aim: To define and describe the toxicities of oral valproic acid (VPA) administered twice daily at does 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. Secondary Aims: To measure the steady state serum trough concentration of free VPA at the targeted total trough VPA concentrations. To evaluate the prhamacokinetic profile of twic daily VPA administration in children. To evaluate the steady state histone acetylation status of peripheral blood monocytes at the targeted trough VPA concentrations. To investigate potential correlations between histone acetylation and free or total VPA trough concentrations. To preliminarily define the antitumor activity of VPA within the confines of a Phase 1 trial.