PHASE I TRIAL OF IRINOTECAN AND TOMUDEX IN COMBINATION ON AN EVERY THREE WEEK SCHEDULE
OBJECTIVES: I. Determine the maximum tolerated dose of ICI D1694 (TDX) when given with
irinotecan (CPT-11) every 3 weeks in patients with advanced solid malignancies. II. Describe
the pharmacokinetics of TDX and CPT-11 when given in combination. III. Investigate the
relationship between topoisomerase I expression in peripheral mononuclear cells and
myelosuppression and/or gastrointestinal toxicity. IV. Investigate the effect of CPT-11 on
thymidylate synthase expression in tumor.
OUTLINE: This is a dose-escalating study to determine the maximum tolerated dose (MTD) of
ICI D1694 (TDX) given in combination with irinotecan. Irinotecan is given intravenously on
day 1 and ICI D1694 intravenously on day 2. Treatment is repeated every 3 weeks until
disease progression or unacceptable toxicity intervenes. Cohorts of 3-6 patients receive
escalated doses of TDX until the MTD is defined; an additional 10-12 patients will be
entered at the MTD to confirm this as a recommended phase II dose.
PROJECTED ACCRUAL: 30-35 patients will be entered.
Primary Purpose: Treatment
Peter J. O'Dwyer, MD, BCh
Abramson Cancer Center of the University of Pennsylvania
United States: Federal Government
|University of Pennsylvania Cancer Center||Philadelphia, Pennsylvania 19104|