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

Colorectal Cancer Clinical Trial

Official title:

Hepatic Resection Followed by Concurrent Adjuvant Portal Vein Infusion of Fluorodeoxyuridine and Systemic 5-Fluorouracil and Folinic Acid for Metastatic Colorectal Carcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00002842
• Other study ID #: 94080
• Secondary ID: P30CA033572CHNMC
• Status: Completed
• Phase: Phase 2
• First received: November 1, 1999
• Last updated: June 3, 2015
• Start date: September 1994
• Est. completion date: May 2014

Study information

• Verified date: June 2015
• Source: City of Hope Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: May 2014
• Est. primary completion date: May 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms
• Metastatic Cancer
• Neoplasm Metastasis

Intervention

Drug:
• floxuridine
Starting dose of 0.2 mg/kg/day for 14 consecutive days.
• fluorouracil
300 mg/m2/day by intravenous bolus 24 hours apart for 5 consecutive days.
• 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.

Procedure:
• adjuvant therapy
Chemotherapy given after hepatic resection
• conventional surgery
Hepatic resection

Locations

Country	Name	City	State
United States	City of Hope Comprehensive Cancer Center	Duarte	California

Sponsors (2)

Lead Sponsor	Collaborator
City of Hope Medical Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To evaluate the effect of hepatic resection of colorectal carcinoma followed by systemic chemotherapy on 2 year disease free survival .		2 years after treatment	No