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

临床试验：PBTC-019：INTR 的 I 期药代动力学最佳剂量研究

• 批准号: 8166672
• 负责人: SUSAN M. BLANEY
• 金额: $ 0.42万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-12-01 至 2010-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8166672
• 关键词: Adult; Antineoplastic Agents; Biological Markers; Blood - brain barrier anatomy; Breast; Central Nervous System Neoplasms; Cerebrum; Child; Clinical Trials; Computer Retrieval of Information on Scientific Projects Database; Development; Disease; Dose; Dose-Limiting; Drug Kinetics; Funding; Glioma; Grant; Image; Institution; Intrathecal Chemotherapy; Intraventricular; Lactones; Leptomeninges; Malignant Neoplasms; Matrix Metalloproteinases; Meninges; Metastatic Neoplasm to the Leptomeninges; Neuroblastoma; Patients; Pediatric Neoplasm; Phase; Prevention; Progression-Free Survivals; Recurrence; Research; Research Personnel; Resources; Retinoblastoma; Rhabdomyosarcoma; Site; Solid Neoplasm; Source; Topotecan; Toxic effect; United States National Institutes of Health; Vascular Endothelial Growth Factors; chemotherapy; cytotoxic; leukemia/lymphoma; lung small cell carcinoma; medulloblastoma; novel; response; tumor

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. Intrathecal topotecan will have anti-tumor activity in children with neoplastic meningitis. 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. The meninges, protected by the blood-brain barrier from the cytotoxic effects of systemic anticancer chemotherapy, are an increasingly recognized site of tumor recurrence in both children and adults. Leukemias and lymphomas are the most common cancers with a predilection for leptomeningeal dissemination. However, a variety of solid tumors including breast or small cell lung cancers; primary central nervous system tumors (CNS) such as medulloblastoma and glioma; and childhood tumors such as neuroblastoma, retinoblastoma and rhabdomyosarcoma, may also disseminate to the leptomeninges. Intrathecal administration of anticancer drugs has been an effective strategy in the treatment and prevention of leptomeningeal leukemias and lymphomas. However, intrathecal chemotherapy has not had a dramatic impact on the progression free survival for patients with neoplastic meningitis from underlying solid tumors; in part due to the extremely limited number of agents available for intrathecal administration. Therefore, the development of new intrathecal agents with novel mechanisms of action is essential.

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， 因此可以在其他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。 鞘内注射托泊替康对肿瘤性脑膜炎患儿具有抗肿瘤活性。 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。 脑膜受血脑屏障的保护，免受全身抗癌化疗的细胞毒性作用，是儿童和成人肿瘤复发的一个越来越被认可的部位。白血病和淋巴瘤是最常见的癌症，易发生软脑膜播散。然而，各种实体瘤，包括乳腺癌或小细胞肺癌;原发性中枢神经系统肿瘤（CNS），如髓母细胞瘤和神经胶质瘤;以及儿童肿瘤，如神经母细胞瘤、视网膜母细胞瘤和横纹肌肉瘤，也可能扩散到软脑膜。鞘内注射抗癌药物是治疗和预防软脑膜白血病和淋巴瘤的有效策略。然而，鞘内化疗对来自基础实体瘤的肿瘤性脑膜炎患者的无进展生存期没有显著影响;部分原因是可用于鞘内给药的药物数量极其有限。因此，开发具有新作用机制的新型鞘内药物至关重要。