REBECCAMYCIN AND OXALIPLATIN FOR SOLID TUMORS

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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.