Liver Resection and Floxuridine Plus Fluorouracil and Leucovorin in Treating Patients With Liver Metastases From Colorectal Cancer

NCT ID: NCT00002842

Last Updated: 2017-04-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 49 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1994-09-30
• Study Completion Date: 2014-05-31

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug and giving drugs in different ways may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of surgery followed by floxuridine plus systemic fluorouracil and leucovorin in treating patients with liver metastases from colorectal cancer.

Detailed Description

OBJECTIVES:

• Evaluate the efficacy of hepatic resection followed by portal vein infusion of floxuridine plus systemic fluorouracil/leucovorin calcium in patients with metastatic colorectal cancer.
• Study the toxic effects of adjuvant chemotherapy following hepatic resection.
• Evaluate mRNA expression of enzymes that may be important to the cytotoxicity of fluoropyrimidines in tumor cells, including thymidylate synthase, ribonucleotide reductase, and folylglutamyl synthetase, by polymerase chain reaction and immunohistochemistry.

OUTLINE: Following resection of the liver and all extrahepatic colorectal cancer, patients receive floxuridine via portal vein infusion from days 1-14. Systemic chemotherapy consists of leucovorin calcium on days 8-14 and fluorouracil on days 9-13. Courses repeat every 4 weeks for a total of 12 weeks.

If biopsy-proven metastatic disease develops, treatment may be stopped at the investigator's discretion. Continuation of regional therapy should be considered for extrahepatic failure. No concurrent radiotherapy is permitted.

Patients are followed every 3 months for 3 years, then every 6 months for survival.

PROJECTED ACCRUAL: It is expected that 50 patients will be entered over approximately 5 years.

Conditions

Colorectal Cancer; Metastatic Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Hepatic Resection/Portal Vein FUdr/Systemic 5-FU & Leucovorin

Patients receive floxuridine via portal vein infusion from days 1-14. Systemic chemotherapy consists of leucovorin calcium on days 8-14 and fluorouracil on days 9-13. Courses repeat every 4 weeks for a total of 12 weeks

Group Type: EXPERIMENTAL

floxuridine

Intervention Type: DRUG

Starting dose of 0.2 mg/kg/day for 14 consecutive days.

fluorouracil

Intervention Type: DRUG

300 mg/m2/day by intravenous bolus 24 hours apart for 5 consecutive days.

leucovorin calcium

Intervention Type: DRUG

500 mg/m2/day by continuous intravenous infusion beginning 24 hours prior to the first dose of 5-FU and continuing until 12 hours following the last dose of 5-FU.

adjuvant therapy

Intervention Type: PROCEDURE

Chemotherapy given after hepatic resection

conventional surgery

Intervention Type: PROCEDURE

Hepatic resection

Interventions

floxuridine

Starting dose of 0.2 mg/kg/day for 14 consecutive days.

Intervention Type: DRUG

fluorouracil

300 mg/m2/day by intravenous bolus 24 hours apart for 5 consecutive days.

Intervention Type: DRUG

leucovorin calcium

500 mg/m2/day by continuous intravenous infusion beginning 24 hours prior to the first dose of 5-FU and continuing until 12 hours following the last dose of 5-FU.

Intervention Type: DRUG

adjuvant therapy

Chemotherapy given after hepatic resection

Intervention Type: PROCEDURE

conventional surgery

Hepatic resection

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed colorectal carcinoma or radiologically confirmed colorectal carcinoma in a synchronous metastasis
• Intrahepatic metastases required

• No more than 15 metastases involving no more than 60% of functioning liver
• No extrahepatic disease unless:

• Resectable anastomotic or locally recurrent tumor
• Resectable mesenteric lymph node involvement in patients undergoing initial resection of primary colorectal carcinoma
• Disease extension from liver metastasis amenable to en bloc resection (e.g., diaphragm wall, kidney, abdominal wall)
• No biopsy-proven chronic active hepatitis

PATIENT CHARACTERISTICS:

Age:

• Physiologic 18 to 70

Performance status:

• Karnofsky 60%-100%

Hematopoietic:

• AGC at least 1,500
• Platelets at least 100,000

Hepatic:

• Bilirubin no greater than 2.0 mg/dL (unless reversibly obstructed by metastasis)

Renal:

• Creatinine no greater than 2.0 mg/dL

Other:

• No second malignancy within 5 years except adequately treated:

• Nonmelanomatous skin cancer
• In situ bladder cancer
• In situ cervical cancer
• No pregnant women

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• Prior mitomycin or nitrosoureas allowed

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior radiotherapy to the liver
• At least 3 weeks since radiotherapy and recovered
• Prior pelvic radiotherapy allowed
• No planned concurrent radiotherapy

Surgery:

• Not specified

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

City of Hope Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lucille A. Leong, MD

Role: STUDY_CHAIR

City of Hope Comprehensive Cancer Center

Locations

City of Hope Comprehensive Cancer Center

Duarte, California, United States

Countries

United States

Other Identifiers

P30CA033572

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CHNMC-IRB-94080

Identifier Type: -

Identifier Source: secondary_id

NCI-V96-1031

Identifier Type: -

Identifier Source: secondary_id

CDR0000065077

Identifier Type: REGISTRY

Identifier Source: secondary_id

94080

Identifier Type: -

Identifier Source: org_study_id