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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
City of Hope Medical Center
ClinicalTrials.gov Identifier:
NCT00002842
First received: November 1, 1999
Last updated: May 28, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Colorectal Cancer
Metastatic Cancer
Drug: floxuridine
Drug: fluorouracil
Drug: leucovorin calcium
Procedure: adjuvant therapy
Procedure: conventional surgery
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Hepatic Resection Followed by Concurrent Adjuvant Portal Vein Infusion of Fluorodeoxyuridine and Systemic 5-Fluorouracil and Folinic Acid for Metastatic Colorectal Carcinoma

Resource links provided by NLM:


Further study details as provided by City of Hope Medical Center:

Primary Outcome Measures:
  • To evaluate the effect of hepatic resection of colorectal carcinoma followed by systemic chemotherapy on 2 year disease free survival . [ Time Frame: 2 years after treatment ] [ Designated as safety issue: No ]

Enrollment: 49
Study Start Date: September 1994
Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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
Drug: floxuridine
Starting dose of 0.2 mg/kg/day for 14 consecutive days.
Drug: fluorouracil
300 mg/m2/day by intravenous bolus 24 hours apart for 5 consecutive days.
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.
Procedure: adjuvant therapy
Chemotherapy given after hepatic resection
Procedure: conventional surgery
Hepatic resection

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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00002842

Locations
United States, California
City of Hope Comprehensive Cancer Center
Duarte, California, United States, 91010-3000
Sponsors and Collaborators
City of Hope Medical Center
Investigators
Study Chair: Lucille A. Leong, MD Beckman Research Institute
  More Information

Additional Information:
No publications provided

Responsible Party: City of Hope Medical Center
ClinicalTrials.gov Identifier: NCT00002842     History of Changes
Other Study ID Numbers: 94080, P30CA033572, CHNMC-IRB-94080, NCI-V96-1031, CDR0000065077
Study First Received: November 1, 1999
Last Updated: May 28, 2014
Health Authority: United States: Federal Government

Keywords provided by City of Hope Medical Center:
stage IV colon cancer
stage IV rectal cancer
recurrent colon cancer
recurrent rectal cancer
liver metastases

Additional relevant MeSH terms:
Colorectal Neoplasms
Neoplasm Metastasis
Colonic Diseases
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Neoplasms
Neoplasms by Site
Neoplastic Processes
Pathologic Processes
Rectal Diseases
Floxuridine
Fluorouracil
Levoleucovorin
Antidotes
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014