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

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

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.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer; Metastatic Cancer
• Intervention / Treatment: Drug: floxuridine; Drug: fluorouracil; Drug: leucovorin calcium; Procedure: adjuvant therapy; Procedure: conventional surgery

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.

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010-3000
      • City of Hope Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
2 Year Disease-free Survival .	Estimated using the product-limit method of Kaplan and Meier. Disease free survival, defined as first documented evidence of treatment failure. Acceptable evidence includes: Anastomotic - positive cytology or biopsy; Abdominal, pelvic and retroperitoneal nodes - progressively enlarging node as evidenced by 2 CT scans separated by at least a 4 week interval, ureteral obstruction in the presence of a mass as documented on CT scan; Peritoneum - positive cytology or biopsy, progressively enlarged intraperitoneal solid mass as evidenced by 2 CT scans separated by at least 4 weeks; Ascites - positive cytology or biopsy; Liver - positive cytology or biopsy; Pelvic mass - positive cytology or biopsy, progressively enlarging intrapelvic solid mass as evidenced by 2 CT scans separated by at least 4 weeks; Abdominal wall - positive cytology or biopsy; Lung - positive cytology or biopsy or presence of multiple pulmonary nodules; Bone marrow - positive cytology, aspiration or biopsy.	2 years after treatment

Collaborators and Investigators

• Sponsor: City of Hope Medical Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Lucille A. Leong, MD, City of Hope Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start: September 1, 1994
• Primary Completion (ACTUAL): May 1, 2014
• Study Completion (ACTUAL): May 1, 2014

Study Registration Dates

• First Submitted: November 1, 1999
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (ESTIMATE): January 27, 2003

Study Record Updates

• Last Update Posted (ACTUAL): April 11, 2017
• Last Update Submitted That Met QC Criteria: February 28, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: stage IV rectal cancer; stage IV colon cancer; recurrent colon cancer; recurrent rectal cancer; liver metastases
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Micronutrients; Vitamins; Calcium-Regulating Hormones and Agents; Antidotes; Vitamin B Complex; Fluorouracil; Leucovorin; Calcium; Levoleucovorin; Floxuridine
• Other Study ID Numbers: 94080; P30CA033572 (U.S. NIH Grant/Contract); CHNMC-IRB-94080; NCI-V96-1031; CDR0000065077 (REGISTRY: NCI PDQ)