Trial Information

A Phase I Study Of Hepatic Arterial Infusion With Floxuridine And Dexamethasone In Combination With Intravenous Oxaliplatin Plus 5-Fluorouracil And Leucovorin In Patients With Unresectable Hepatic Metastases From Colorectal Cancer

OBJECTIVES:

- Determine the maximum tolerated dose of oxaliplatin and fluorouracil when given with
leucovorin calcium and hepatic intra-arterial floxuridine and dexamethasone with or
without cryosurgery (group I cryosurgery closed to accrual as of 10/13/03) in patients
with unresectable liver metastases from colorectal cancer.

- Determine, preliminarily, the anti-tumor activity of this regimen in these patients.

OUTLINE: This is a dose-escalation study of oxaliplatin and fluorouracil. Patients are
assigned to one of two treatment groups. (Group I closed to accrual as of 10/13/03.)

- Group I (closed to accrual as of 10/13/03): Patients with no more than 8 hepatic
metastases and no metastases greater than 5 cm in diameter undergo cryosurgery prior to
chemotherapy. Chemotherapy is delayed for at least 4 weeks after cryosurgery.

- Group II: Patients with more than 8 hepatic metastases or at least one metastases
greater than 5 cm in diameter do not undergo cryosurgery prior to chemotherapy.

Beginning 2 weeks after pump placement surgery, all patients receive floxuridine and
dexamethasone by hepatic intra-arterial infusion continuously on days 1-14; oxaliplatin IV
over 2 hours and leucovorin calcium IV over 2 hours on days 15 and 29; and fluorouracil IV
continuously over 48 hours on days 15-16 and 29-30. Courses repeat every 36 days in the
absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of oxaliplatin and fluorouracil until the
maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at
which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

PROJECTED ACCRUAL: Approximately 4-72 patients will be accrued for this study within 18
months.