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

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CC-5013的儿科I期试验，将在患有复发性或难治性中枢神经系统肿瘤的儿童中进行，以确定CC-5013在该儿科人群中的最大耐受剂量（MTD）和安全性。这是儿童脑肿瘤协会的一项合作研究，在全国12个中心提供。CC-5013将以胶囊形式给予，每天口服一次，为期21天，为期28天。它是一种类似沙利度胺的药物，具有广泛的药理学、抗血管生成和免疫作用。课程可以持续一年，前提是受试者没有出现不可接受的毒性、疾病进展或其他禁忌症，如怀孕。计划9个剂量水平，并将使用改进的连续再评估方法，使得在每个剂量水平上至少招收2名患者。本研究的目的是：评估复发性或难治性原发性中枢神经系统肿瘤儿童口服CC-5013的MTD，每日一次，共21天，为期28天，描述CC-5013在复发性或难治性原发性中枢神经系统肿瘤儿童中的毒性特征，确定CC-5013的剂量限制性毒性，表征CC-5013在儿童和青少年中的药代动力学特征，表征CC-5013在儿童和青少年中的药物遗传学特征，评估循环内皮细胞的变化CC-5013治疗患者CECs和循环内皮细胞前体（cep）的变化，探讨CECs和cep与血浆、血清和尿液中血小板反应蛋白、b-FGF、TNF-、IL-12、IL-8和VEGF等血管生成相关蛋白的变化之间的相关性，并将这些变化与MR灌注和临床结局的变化联系起来。评价治疗期间MR光谱、MR灌注和MR扩散的变化

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