REBECCAMYCIN AND OXALIPLATIN FOR SOLID TUMORS

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。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。所列机构为中心，不一定是研究者所在机构。这是一项XL 119（瑞贝卡霉素类似物）联合奥沙利铂治疗18岁及以上难治性实体瘤患者的双中心I期临床试验。本研究的目的是确定XL 119与奥沙利铂联合给药的最大耐受剂量（MTD），确定该联合给药的剂量限制性毒性，并确定这两种药物联合给药时的药代动力学。奥沙利铂和XL 119联合治疗的动力来自：1）数据表明顺铂和XL 119之间可能存在协同作用，2）这两种药物的毒性不重叠，3）XL 119和奥沙利铂在胆道癌中具有活性的早期证据，以及4）铂类药物和拓扑异构酶抑制剂之间的已知协同作用。临床前数据显示XL 119对白血病、黑色素瘤、肉瘤和肺癌的活性。在本研究中，XL 119将连续5天通过中心线给药超过1小时。奥沙利铂将在第5天XL 119给药后立即给药2小时。这个循环每三周重复一次。MTD将根据第一个疗程期间观察到的毒性定义。如方案所述，将在每个队列内进行剂量递增。将在GCRC观察受试者，以采集第1周的药代动力学样本。本研究共入组15例受试者。

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 dual-center, phase I clinical trial of XL119 (rebeccamycin analogue) combined with oxaliplatin for patients age 18 and over with refractory solid tumors. The objectives of this study are to determine the maximum tolerated dose (MTD) of XL119 given in conjunction with oxaliplatin, to determine the dose limiting toxicities of this combination, and to determine the pharmacokinetics of these two agents when given in combination. The impetus for combining oxaliplatin and XL119 stems from: 1) data suggesting possible synergy between cisplatin and XL119, 2) non-overlapping toxicities of these two agents, 3) early evidence of activity for both XL119 and oxaliplatin in biliary cancers, and 4) known synergy between platinum agents and topoisomerase inhibitors. Preclinical data shows activity of XL119 against leukemia, melanoma, sarcoma and lung cancer. In this study, XL119 will be given over 1 hour through a central line on five consecutive days. Oxaliplatin will be administered over two hours immediately after the XL119 on Day 5. This cycle is repeated every three weeks. MTD will be defined based on the toxicities observed during the first course of treatment. Dose escalation will proceed within each cohort as detailed in the protocol. Subjects will be seen at the GCRC for the collection of pharmacokinetic samples during Week 1. A total of 15 subjects will be enrolled in this study.