Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Completed	18 and over	NCI	MSKCC-98072 MSKCC-98072A(9), NCI-H99-0024, NCT00003753

Objectives

1. 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.)
2. Determine the efficacy of this combination chemotherapy after liver resection, in terms of 2-year survival and 2-year recurrence rates, in these patients.
3. Determine the pharmacokinetic effects of intrahepatic FUDR and liver resection on the metabolism of irinotecan to its active metabolite, SN-38 in these patients.
4. Determine the safety and efficacy of the pump used in delivering intra-arterial chemotherapy to the liver in these patients.

Entry Criteria

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

Prior/Concurrent Therapy:

Biologic therapy:

• Not specified

Chemotherapy:

• At least 4 weeks since prior chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior radiotherapy to the liver
• At least 4 weeks since prior radiotherapy to the pelvis

Surgery:

• See Disease Characteristics

Patient Characteristics:

Age:

• 18 and over

Performance status:

• Karnofsky 60-100%

Life expectancy:

• Not specified

Hematopoietic:

• WBC at least 3,000/mm³
• Absolute neutrophil count at least 1,500/mm³
• Platelet count at least 100,000/mm³

Hepatic:

• Bilirubin no greater than 1.5 mg/dL

Renal:

• Not specified

Other:

• Not pregnant or nursing
• No active infection

Expected Enrollment

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.

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.

Trial Contact Information

Trial Lead Organizations

Memorial Sloan-Kettering Cancer Center

Nancy Kemeny, MD, Protocol chair		Ph: 212-639-8068; 800-525-2225

Registry Information
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
Trial Start Date		1998-09-08
Registered in ClinicalTrials.gov		NCT00003753
Date Submitted to PDQ		1999-01-25
Information Last Verified		2004-08-11
NCI Grant/Contract Number		CA08748, CA61524

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