EPOTHILONE B ANALOGUE BMS-247550 IN PTS WITH MALIGNANCIES & LIVER DYSFUNCTION

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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. BMS-247550 is a semi-synthetic analog of the natural product epothilone B, specifically designed to overcome the metabolic instability of the natural product. Similar to paclitaxel, BMS-247550 blocks cells in the mitotic phase of the cell division cycle and is a highly potent cytotoxic agent capable of killing cancer cells at low nanomolar concentration. BMS-247550 has demonstrated impressive antitumor activity in a number of preclinical human tumor models. This is a multi-center Phase I trial to define the levels of hepatic impairment at which dose modifications of BMS-247550 are required. The study will have four parallel groups of patients with different degrees of liver dysfunction (normal, mild, moderate and severe) and follow dose-escalation as detailed in the protocol. All subjects will receive premedication to minimize hypersensitivity reactions. Subjects will receive the study drug by intravenous infusion over three hours on the first day of every 21-day cycle. Subjects may repeat cycles until disease progression or unacceptable side effects. Subjects will have first infusion at the GCRC and stay overnight for pharmacokinetics. Subjects will return to the GCRC for 3 outpatient visits for pharmacokinetics as well. 84 subjects will be enrolled at all sites and 8 subjects are expected at this site.