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

ADVL0419：丙戊酸在复发/进展儿童中的 A 期 1 研究

• 批准号: 7376226
• 负责人: NITA L. SEIBEL
• 金额: $ 0.05万
• 依托单位: CHILDREN'S RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-12-01 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7376226
• 关键词: ADVL0419; APHASE; STUDY; VALPROIC; ACID

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.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。本研究的主要目的是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）每日两次口服给药（维持血清谷浓度100-150 mcg/ml或150-200 mcg/ml所需剂量）的毒性。次要目的是：1）在目标总VPA谷浓度下测量游离VPA血清谷浓度的稳态。2)评价儿童VPA每日两次给药的药代动力学特征。3)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。4)研究组蛋白乙酰化与游离或总丙戊酸钠谷浓度之间的潜在相关性。5)在I期试验范围内初步确定VPA的抗肿瘤活性。