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

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。这是一项I期试验，旨在评估CLORETAZINE¿（VNP40101M）的最大耐受剂量（MTD）和剂量限制毒性（dlt），每6周静脉注射5天，用于复发性、进行性或难治性原发性脑肿瘤的儿童。MTD将分为两层：a)第1层：先前未接受过XRT或仅接受局灶性XRT和/或两次既往骨髓抑制化疗或生物治疗方案的患者。主要目标：1；评估氯噻嗪（VNP40101M）对复发性、进展性或难治性原发性脑肿瘤儿童每6周静脉注射5天时的MTD和DLT。次要目标：1；研究氯噻嗪（VNP40101M）及其活性代谢物VNP4090CE在复发性、进展性或难治性原发性脑肿瘤患儿中的药代动力学。2. 评估暴露于CLORETAZINE¿（VNP40101M）后复发性、进行性或难治性原发性脑患儿外周血单个核细胞（PBMC）中烷基鸟嘌呤烷基转移酶（AGT）的耗竭。3. 获得氯噻嗪（VNP40101M）治疗复发性、进展性或难治性儿童原发性脑肿瘤疗效的初步证据。

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.