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

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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.