PBTC-025-A PHASE I PHARMACOPKINETIC AND SAFETY STUDY IN CHILDREN

PBTC-025-A 儿童 I 期药代动力学和安全性研究

• 批准号: 8356726
• 负责人: SUSAN M. BLANEY
• 金额: $ 0.63万
• 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/8356726
• 关键词: Adolescent; Central Nervous System Neoplasms; Cerebrospinal Fluid; Child; Clinical Research; Correlative Study; Dose; Drug Kinetics; Formalin; Freezing; Funding; Genomics; Grant; Methods; National Center for Research Resources; PTCH gene; Paraffin Embedding; Pathologic; Pathway interactions; Patients; Pharmaceutical Preparations; Phase; Phase II Clinical Trials; Plasma; Principal Investigator; Recurrence; Refractory; Research; Research Design; Research Infrastructure; Resources; SHH gene; Safety; Schedule; Signal Pathway; Source; Tissues; Toxic effect; United States National Institutes of Health; base; cost; medulloblastoma; pharmacokinetic characteristic; phase 2 study; safety study

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. ABSTRACT This is a multi-center, phase I type trial for children with recurrent or refractory medulloblastoma to select recommend a pharmacokinetic based daily dose of GDC-0449 for a subsequent Phase II trial to evaluate toxicity and to characterize the pharmacokinetics and biologics of the GDC-0449. I. HYPOTHESIS The proposed phase I type study of GDC 0449 will seek to describe the toxicities and pharmacokinetic characteristics of the drug in patients with recurrent or refractory medulloblastoma. Correlative studies on formalin fixed paraffin embedded tissue and snap frozen tissue (when available) will seek to select patients in whom the PTCH/SHH signaling pathway is activated. This information will be used in subsequent Phase II study so as to select a group of patients that are biologically optimal for treatment with this targeted therapy. II. SPECIFIC AIMS Primary Objectives: 1. To select, based on safety and pharmacokinetics, a daily dose of GDC0449 to recommend for a subsequent PBTC Phase II trial of children with recurrent or refractory medulloblastoma. Secondary Objectives: 1. To document and describe toxicities associated with GDC-0449 administered on a daily schedule. 2. To characterize the pharmacokinetics (plasma and cerebrospinal fluid) of GDC-0449 in children/adolescents with refractory medulloblastoma. 3. To document preliminary antitumor activity in patients with recurrent or refractory medulloblastoma treated with GDC-0449. 4. To document pathologic and genomic methods to identify CNS tumors with activation of the PTCH/SHH pathway.

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。 摘要 这是一项针对复发或难治性髓母细胞瘤儿童的多中心I期试验，旨在为后续的II期试验选择推荐的基于药代动力学的每日剂量的GDC-0449，以评估毒性并表征GDC-0449的药代动力学和生物制品。 一、假说 拟议的GDC 0449的I期研究将试图描述该药物在复发或难治性髓母细胞瘤患者中的毒性和药代动力学特征。对福尔马林固定的石蜡包埋组织和速冻组织(如果有)的相关研究将寻求选择PTCH/SHH信号通路被激活的患者。这些信息将被用于随后的第二阶段研究，以便选择一组生物学上最优的患者进行这种靶向治疗。 二、具体目标 主要目标： 1.根据安全性和药代动力学，选择每日剂量的GDC0449，以推荐用于随后对复发或难治性髓母细胞瘤儿童进行PBTC II期试验。 次要目标： 1.记录和描述与按每日计划服用GDC-0449有关的毒性。 2.研究GDC-0449在儿童/青少年难治性髓母细胞瘤中的药代动力学(血浆和脑脊液)。 3.研究GDC-0449治疗复发性或难治性髓母细胞瘤患者的初步抗肿瘤活性。 4.记录PTCH/SHH通路激活的中枢神经系统肿瘤的病理学和基因组学方法。