A PHASE I STUDY OF ZOLEDRONIC ACID (ZOMETA) WITH CYCLOPHOSPHAMIDE IN CHILDREN

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 假设 对于复发或难治性神经母细胞瘤患者，Zometa将被耐受和有效。 具体目标 主要目的：1.确定复发性或难治性神经母细胞瘤患儿在28天疗程中静脉滴注Zometa 15分钟，同时口服固定剂量环磷酰胺的最大耐受量。2.测定本附表所列佐美他的毒性。 次要目标：1.在I期研究范围内，初步评价佐美他联合口服环磷酰胺治疗儿童复发和/或难治性神经母细胞瘤的抗肿瘤活性。2.评价Zometa在儿童复发性或难治性神经母细胞瘤中的药代动力学行为。3.通过对骨吸收标记物、细胞因子和骨相关生长因子、γ-Delta T细胞变化的相关性研究，初步了解Zometa在神经母细胞瘤中的生物活性。

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. HYPOTHESIS Zometa will be tolerated and active in patients with recurrent or refractoryneuroblastoma. SPECIFIC AIMS Primary Aims: 1. To determine the maximum tolerated dose of Zometa given as a 15 minute intravenous infusion with a fixed dose of concomitant oral cyclophosphamide when administered in 28 day courses to children with recurrent or refractory neuroblastoma. 2. To determine the toxicities of Zometa given on this schedule. Secondary Aims: 1. To preliminarily evaluate the antitumor activity of Zometa and concomitant oral cyclophosphamide in children with recurrent and/or refractory neuroblastoma within the confines of a Phase I study. 2. To evlauate the pharmacokinetic behavior of Zometa in children with recurrent or refractory neuroblastoma. 3. To obtain preliminary information about the biologic activity of Zometa in neuroblastoma through correlative studies assessing change in markers of bone resorption, cytokines and bone-related growth factors, and gamma-delta T-cells.