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

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 假设 Zometa在复发性或难治性神经母细胞瘤患者中具有耐受性和活性。 具体目标 主要目标：1。 确定复发性或难治性神经母细胞瘤儿童28天疗程中Zometa 15分钟静脉输注联合固定剂量口服环磷酰胺的最大耐受剂量。 2. 确定按此时间表给予Zometa的毒性。 次要目标：1。 在I期研究范围内，初步评价Zometa联合口服环磷酰胺治疗复发性和/或难治性神经母细胞瘤儿童的抗肿瘤活性。 2. 评价Zometa在复发性或难治性神经母细胞瘤儿童中的药代动力学行为。 3. 通过评估骨吸收标志物、细胞因子和骨相关生长因子以及γ-δ T细胞变化的相关研究，获得Zometa在神经母细胞瘤中生物活性的初步信息。

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.