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

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 假设： 鞘内注射拓扑替康对患有肿瘤性脑膜炎的儿童具有抗肿瘤活性。 具体目标： 主要目标 1.测定连续5天每日脑室注射拓扑替康的MTD。 2.描述拓扑替康脑室给药的毒性，并确定其剂量限制毒性。 每日一次，连续5天。 3.确定脑室注射拓扑替康的MTD是否也是拓扑替康定义的药代动力学最佳剂量 脑脊液中的内酯浓度。 次要目标 1.初步描述脑室注射拓扑替康的抗肿瘤活性。 将在这项试验中治疗的异质疾病。 2.探讨肿瘤性脑膜炎患者脑脊液中基质金属蛋白酶、血管内皮生长因子等潜在生物学指标的变化。 在脑室内使用拓扑替康之前和整个治疗过程中。 3.进一步描述拓扑替康在脑脊液中的药代动力学。 4.探讨治疗后中心回顾成像的可行性，并将观察到的效果与 对脑室内治疗的反应。

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.