PBTC016: A PHASE I, MOLECULAR BIOLOGY AND PHASE II STUDY OF LAPATINIB (GW5720A

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来源获得了主要资金，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。这是一项I期试验，旨在评估氯瑞他嗪？（VNP 40101 M）的最大耐受剂量（MTD）和剂量限制性毒性（DLT），该药物每6周静脉给药一次，每日一次，连续5天，治疗复发性、进展性或难治性原发性脑肿瘤儿童。将在两个分层中估计MTD：a）分层1：既往未接受XRT或仅接受局灶性XRT和/或既往接受过2种骨髓抑制化疗或生物治疗方案的患者。主要目标：1。估计复发性、进行性或难治性原发性脑肿瘤儿童静脉注射氯瑞他嗪？（VNP 40101 M），每日一次，持续5天，每6周一次的MTD并描述DLT。次要目标：1。描述氯瑞他嗪？（VNP 40101 M）及其活性代谢物VNP 4090 CE在复发性、进行性或难治性原发性脑肿瘤儿童中的药代动力学特征。2.估计暴露于氯瑞他嗪<$（VNP 40101 M）后复发性、进行性或难治性原发性脑肿瘤儿童外周血单核细胞（PBMC）中烷基鸟嘌呤烷基转移酶（AGT）的消耗。 3.获得氯瑞他嗪（VNP 40101 M）治疗复发性、进行性或难治性原发性脑肿瘤儿童的疗效的初步证据。

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. This is a Phase I trial to estimate the maximum tolerated dose (MTD) and dose limiting toxicities (DLTs) of CLORETAZINE¿ (VNP40101M) administered intravenously daily for 5 consecutive days every six weeks to children with recurrent, progressive or refractory primary brain tumors. The MTD will be estimated in two strata: a) Stratum 1: Patients who received no prior XRT or focal XRT only and/or 2 prior myelosuppressive chemotherapy or biological therapy regimens. Primary Objective: 1. To estimate the MTD and describe the DLT of CLORETAZINE¿ (VNP40101M) when administered intravenously daily for 5 days every 6 weeks to children with recurrent, progressive or refractory primary brain tumors. Secondary Objectives: 1. To characterize the pharmacokinetics of CLORETAZINE¿ (VNP40101M), and its active metabolite VNP4090CE, in children with recurrent, progressive or refractory primary brain tumors. 2. To estimate depletion of alkyl guanine alkyltransferase (AGT) in peripheral blood mononuclear cells (PBMC) in children with recurrent, progressive or refractory primary brain after exposure to CLORETAZINE¿ (VNP40101M). 3. To obtain preliminary evidence of efficacy of CLORETAZINE¿ (VNP40101M) in children with recurrent, progressive or refractory primary brain tumors.