CLINICAL TRIAL: PBTC-019: A PHASE I PHARMACOKINETIC OPTIMAL DOSING STUDY OF INT

临床试验：PBTC-019：INT 的 I 期药代动力学最佳剂量研究

• 批准号: 8356671
• 负责人: SUSAN M. BLANEY
• 金额: $ 0.91万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-12-01 至 2011-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8356671
• 关键词: Biological Markers; Cerebrum; Child; Clinical Research; Clinical Trials; Disease; Dose; Dose-Limiting; Drug Kinetics; Funding; Grant; Image; Intraventricular; Lactones; Matrix Metalloproteinases; Metastatic Neoplasm to the Leptomeninges; National Center for Research Resources; Patients; Phase; Principal Investigator; Research; Research Infrastructure; Resources; Source; Topotecan; Toxic effect; United States National Institutes of Health; Vascular Endothelial Growth Factors; cost; response; tumor

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Hypothesis: Intrathecal topotecan will have anti-tumor activity in children with neoplastic meningitis. Specific Aims: Primary Objectives 1. To estimate the MTD of intraventricular topotecan administered daily for 5 consecutive days. 2. To describe the toxicities and define the dose-limiting toxicity of topotecan following intraventricular administration daily for 5 consecutive days. 3. To determine if the MTD of intraventricular topotecan is also a pharmacokinetic optimal dose as defined by topotecan lactone concentrations in the cerebral CSF. Secondary Objectives 1. To provide preliminary descriptions of the anti-tumor activity of intraventricular topotecan observed in the heterogeneous diseases that will be treated in this trial. 2. To investigate MMP, VEGF, and other potential biological markers in the CSF of patients with neoplastic meningitis prior to and throughout treatment with intraventricular topotecan. 3. To further describe the CSF pharmacokinetics of topotecan following CSF administration. 4. To investigate the feasibility of central review imaging following treatment and to correlate observed effects with response to intraventricular therapy.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 假设： 鞘内注射托泊替康对肿瘤性脑膜炎患儿具有抗肿瘤活性。 具体目标： 主要目标 1.估计连续5天每天脑室内给予托泊替康的MTD。 2.描述托泊替康脑室内给药后的毒性并确定剂量限制性毒性 每天连续5天。 3.确定脑室内拓扑替康的MTD是否也是拓扑替康定义的药代动力学最佳剂量 脑CSF中的内酯浓度。 次要目的 1.初步描述脑室内注射拓扑替康的抗肿瘤活性， 本试验将治疗的异质性疾病。 2.探讨肿瘤性脑膜炎患者脑脊液中MMP、VEGF及其他潜在生物学标志物的表达 在脑室内托泊替康治疗之前和整个治疗期间。 3.进一步描述CSF给药后托泊替康的CSF药代动力学。 4.研究治疗后中心复查成像的可行性，并将观察到的效应与 对脑室内治疗的反应。