REBECCAMYCIN AND OXALIPLATIN FOR SOLID TUMORS

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。这是一项双中心I期临床试验，XL119 （rebeccamycin类似物）联合奥沙利铂治疗18岁及以上难治性实体瘤患者。本研究的目的是确定XL119与奥沙利铂联合使用的最大耐受剂量（MTD），确定该组合的剂量限制性毒性，以及确定这两种药物联合使用时的药代动力学。奥沙利铂和XL119联合使用的动力源于：1)数据表明顺铂和XL119之间可能存在协同作用，2)这两种药物的毒性不重叠，3)XL119和奥沙利铂在胆道癌中的活性的早期证据，以及4)铂类药物和拓扑异构酶抑制剂之间已知的协同作用。临床前数据显示XL119对白血病、黑色素瘤、肉瘤和肺癌有活性。在本研究中，XL119将连续5天通过中心线给予1小时以上。奥沙利铂将在第5天XL119后立即给予2小时。这个循环每三周重复一次。MTD将根据第一疗程中观察到的毒性来确定。剂量递增将在每个队列中进行，详见方案。受试者将在第1周期间在GCRC收集药代动力学样本。本次研究共纳入15名受试者。

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.