Floxuridine, Dexamethasone, and Irinotecan After Surgery in Treating Patients With Liver Metastases From Colorectal Cancer

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Completed

CT.gov ID

NCT00003753

Collaborator

National Cancer Institute (NCI) (NIH)

Location

Duration (Months)

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as floxuridine, dexamethasone, and irinotecan, use different ways to stop tumor cells from dividing so they stop growing or die. Hepatic arterial infusion uses a catheter to deliver chemotherapy directly to the liver. Combining more than one drug and giving them in different ways may kill any tumor cells remaining after surgery.

PURPOSE: Phase II trial to study the effectiveness of irinotecan combined with hepatic arterial infusion with floxuridine and dexamethasone after surgery in treating patients who have liver metastases from colorectal cancer.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer Metastatic Cancer	Drug: dexamethasone Drug: floxuridine Drug: irinotecan hydrochloride Procedure: adjuvant therapy Procedure: conventional surgery	Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Sep 1, 1998

Actual Primary Completion Date :

Apr 1, 2004

Actual Study Completion Date :

Apr 1, 2004

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically confirmed colorectal adenocarcinoma
Primary colorectal tumor must have been previously resected
Potentially completely resectable hepatic metastases (or removable by cryoresection) without current evidence of other metastatic disease
No extrahepatic sites of disease
No ascites or hepatic encephalopathy