Phase I Pharmacokinetic and Pharmacodynamic Trial of Irinotecan in Combination With Tomudex in Patients With Refractory Solid Malignancies
OBJECTIVES: I. Determine the maximum tolerated dose of irinotecan in combination with
raltitrexed in patients with refractory solid tumors. II. Describe and quantify the toxic
effects of this combination treatment regimen in a minimally pretreated patient population.
III. Determine the pharmacokinetics of this combination treatment regimen. IV. Document any
antitumor activity of this combination treatment regimen in this patient population.
OUTLINE: This is a dose escalation study of irinotecan and raltitrexed. Patients receive
irinotecan IV over 90 minutes on days 1 and 8 followed by raltitrexed IV over 15 minutes on
day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable
toxicity. Cohorts of 3-6 patients each receive escalating doses of irinotecan and
raltitrexed until the maximum tolerated dose (MTD) is determined. The MTD is defined as the
dose preceding that at which 2 of 6 patients experience dose limiting toxicities. Additional
cohorts receive raltitrexed on day 2 rather than day 1 near the final dose levels of the
PROJECTED ACCRUAL: A maximum of 36 patients will be accrued for this study within 1 year.
Primary Purpose: Treatment
Neal J. Meropol, MD
Fox Chase Cancer Center
United States: Federal Government
|Fox Chase Cancer Center||Philadelphia, Pennsylvania 19111|