A PHASE 1 STUDY OF PS-341 IN COMBINATION WITH 5-FU/LV IN 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 Phase I Study with the following objectives: Primary: 1. To determine the dose limiting toxicity (DLT) and maximum tolerated dose (MTD) of PS-341 when administered as an intravenous bolus twice weekly combined with weekly 5-FU and LV in patients with metastatic solid tumors. 2. To evaluate the pharmacodynamics of PS-341 by determining the 20S proteasome and NFkB inhibition in blood of patients treated with intravenous PS-341 combined with weekly 5-FU and LV. Secondary: 1. To identify any objective tumor response in patients treated with intravenous PS-341. 2. To evaluate the relationship between inhibition of the 20S proteasome and NFkB and clinical toxicity. 3. To obtain preliminary data on molecular correlates of response to PS-341 and 5-FU and LV including genes involved in aptosis, cell cycle control, transcriptional regulation and adhesion/angiogenesis based on the mechanisms of PS-341. 4. To examine the pharmacokinetics of 5-FU when co-administered with PS-341.