PBTC-018: A PHASE I TRIAL OF CC-5013 (LENALIDOMIDE

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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 pediatric phase I trial of CC-5013 will be performed in children with recurrent or refractory tumors of the central nervous system, to determine the maximum tolerated dose (MTD) and safety profile of CC-5013 in this pediatric population. It is a collaborative study of the Pediatric Brain Tumor Consortium and is offered at 12 centers nationwide. CC-5013 will be given in capsule form orally once a day for 21 days of a 28-day course. It is an agent similar to thalidomide and has a wide variety of pharmacologic, antiangiogenic and immunologic effects. Courses may continue for one year provided the subject does not develop unacceptable toxicity, disease progression or another contraindicated medical condition such as pregnancy. Nine dose levels are planned and the modified continual reassessment method will be used such that at least two patients are enrolled on each dose level. The objectives of this study are: To estimate the MTD of oral CC-5013 administered to children with recurrent or refractory primary CNS tumors once daily for 21 days of a 28 day course To describe the toxicity profile and define the dose-limiting toxicity of CC-5013 in children with recurrent or refractory primary CNS tumors To characterize the pharmacokinetics of CC-5013 in children and adolescents To characterize the pharmacogenetics of CC-5013 in children and adolescents To evaluate changes in circulating endothelial cells (CECs) and circulating endothelial cell precursors (CEPs) in patients treated with CC-5013, and to investigate the correlation between changes in CECs and CEPs, plasma, serum and urine levels of proteins associated with angiogenesis including thrombospondin, b-FGF, TNF- , IL-12, IL-8 and VEGF, and correlate these changes with changes in MR perfusion and clinical outcome. To evaluate changes in MR spectroscopy, MR perfusion and diffusion during treatment