Trial Information

A Phase I-II Study of Hepatic Arterial Therapy Via Pump (Protocol D97-063) With Floxuridine (FUDR) and Dexamethasone (DEX) in Combination With Intravenous Irinotecan as Adjuvant Treatment After Resection of Hepatic Metastases From Colorectal Cancer

OBJECTIVES:

- Determine the maximum tolerated dose (MTD) of hepatic arterial infusion of floxuridine
(FUDR) and dexamethasone given via an implanted pump in combination with weekly
intravenous irinotecan as adjuvant treatment after resection of hepatic metastases in
patients with hepatic metastases from colorectal cancer. (The MTDs of irinotecan and
floxuridine have been reached as of 10/15/03; phase I closed to accrual as of
10/15/03.)

- Determine the efficacy of this combination chemotherapy after liver resection, in terms
of 2-year survival and 2-year recurrence rates, in these patients.

- Determine the pharmacokinetic effects of intrahepatic FUDR and liver resection on the
metabolism of irinotecan to its active metabolite, SN-38 in these patients.

- Determine the safety and efficacy of the pump used in delivering intra-arterial
chemotherapy to the liver in these patients.

OUTLINE: This is a dose-escalation* study of floxuridine and irinotecan.

Patients undergo hepatic resection and pump placement into the abdomen. About 4 weeks after
surgery, patients receive irinotecan IV over 30 minutes on days 1 and 15. Patients also
receive floxuridine and dexamethasone intra-arterially via an implanted pump continuously on
days 1-14. Treatment repeats every 28 days for 6 courses in the absence of unacceptable
toxicity or disease progression.

Sequential dose escalation of irinotecan is followed by sequential dose escalation of
floxuridine. Cohorts of 3-6 patients receive escalating doses of irinotecan and floxuridine
until the maximum tolerated doses (MTDs) are determined. The MTD* (phase II dose) is defined
as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.

NOTE: *The MTDs of irinotecan and floxuridine have been reached as of 10/15/03; phase I
closed to accrual as of 10/15/03

Patients are followed every 3 months for 2 years, every 4 months for 2-4 years, and then
every 6 months thereafter.

PROJECTED ACCRUAL: A total of 2-24 patients will be accrued for the phase I portion of this
study within 1 year (phase I closed to accrual as of 10/15/03). A total of 50 additional
patients will be accrued for this study at the phase II dose level.