REBECCAMYCIN AND OXALIPLATIN FOR SOLID TUMORS

瑞贝卡霉素和奥沙利铂治疗实体瘤

• 批准号: 7378058
• 负责人: AFSHIN DOWLATI
• 金额: $ 1.65万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7378058
• 关键词: REBECCAMYCIN; OXALIPLATIN; SOLID; TUMORS

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.

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。这是一项双中心、I期临床试验，XL119(瑞贝霉素类似物)联合奥沙利铂治疗18岁及以上的难治性实体瘤患者。本研究的目的是确定XL119与奥沙利铂合用的最大耐受量(MTD)，确定其剂量限制毒性，并确定这两种药物合用时的药代动力学。将奥沙利铂和XL119联合使用的动力来自：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都有效的早期证据，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具有抗白血病、黑色素瘤、肉瘤和肺癌的活性。在这项研究中，XL119将连续5天通过中心线给予超过1小时的治疗。奥沙利铂将在XL119后的第5天立即给药超过两个小时。这个周期每三周重复一次。MTD的定义将基于在第一个疗程中观察到的毒性。剂量递增将在方案中详细说明的每个队列中进行。受试者将在第一周内在GCRC进行药代动力学样本的采集。共有15名受试者将参加这项研究。