Combination Chemotherapy in Treating Patients With Liver Metastases From Colorectal Cancer

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Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
Phase IIITreatmentCompleted18 and overNCI, OtherCDR0000064553
CALGB-9481, ECOG-C9481, NCT00002716

Trial Description


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 may kill more cancer cells. It is not yet known which chemotherapy regimen is more effective for metastatic colorectal cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of intrahepatic floxuridine, leucovorin, and dexamethasone with that of systemic fluorouracil and leucovorin in treating patients who have unresectable liver metastases from colorectal cancer.

Further Study Information


  • Compare the efficacy, toxicity, and cost of hepatic artery infusion of floxuridine, leucovorin calcium (CF), and dexamethasone vs IV fluorouracil and IV CF after resection of primary disease in patients with hepatic metastases secondary to colorectal cancer.
  • Compare the quality of life of patients treated with these regimens.
  • Measure the level of thymidylate synthase present in liver metastases, and correlate these levels with objective response and survival in patients treated with these regimens.
  • Assess the p53 mutations, and correlate findings with objective response and survival in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to center, percentage of liver involvement on CT scan or MRI (less than 30% vs 30% to under 70%), prior chemotherapy (none vs adjuvant chemotherapy comprising fluorouracil (5-FU) and leucovorin calcium (CF) or 5-FU, CF, and levamisole (LEV) completed at least 1 year before study vs adjuvant chemotherapy comprising 5-FU with or without LEV completed at least 6 months before study), and synchronous disease (yes vs no). Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients undergo laparotomy for placement of a hepatic artery catheter and then subcutaneous placement of a hepatic artery infusion pump. Patients with unresected primary disease also undergo resection at the time of catheter and pump placement. Beginning within 1-2 weeks after surgery, patients receive floxuridine, dexamethasone, and leucovorin calcium (CF) via continuous hepatic artery infusion on days 1-14.
  • Arm II: Patients receive CF IV and fluorouracil IV on days 1-5. Patients with unresected primary disease undergo resection within 3-4 weeks before initiation of chemotherapy.

Treatment for patients on both arms continues every 4 weeks in the absence of disease progression or unacceptable toxicity.

Quality of life and medical resource utilization are assessed at baseline, every 3 months for 1 year, and then at 18 months.

Patients are followed every 3 months.

PROJECTED ACCRUAL: Approximately 340 patients (170 per arm) will be accrued for this study within approximately 4.5 years.

Eligibility Criteria


  • Unresectable liver metastases secondary to colorectal cancer
  • Less than 70% liver involvement on CT scan or MRI
  • Liver biopsy required before study unless 1 of the following conditions are met:
  • Carcinoembryonic antigen greater than 30
  • 5 or more liver metastases visible on CT scan or MRI
  • Greater than 50% to under 70% liver involvement on CT scan or MRI
  • Histologically proven primary colorectal cancer that is resected or appears resectable on CT scan and physical exam
  • Documentation of previously resected primaries must be based on pathologic results of the resected tumor
  • Histological documentation of synchronous disease must be based on 1 of the following:
  • Biopsy of primary colorectal tumor before study
  • Suspicious lesion on barium enema, colonoscopy, or sigmoidoscopy, and a liver biopsy positive for adenocarcinoma consistent with the primary colorectal tumor
  • Measurable disease
  • Clearly defined liver mass measuring at least 2 cm or at least 3 liver masses on CT scan or MRI
  • No evidence of extrahepatic disease on CT scan and physical exam
  • No portal vein occlusion or ascites



  • 18 and over

Performance status:

  • Not specified

Life expectancy:

  • Not specified


  • Not specified


  • See Disease Characteristics
  • Bilirubin no greater than 2 times normal


  • Not specified


  • No other malignancy within the past 5 years except inactive nonmelanomatous skin cancer, carcinoma in situ of the cervix, or grade 1 bladder cancer
  • Not pregnant or nursing
  • Fertile patients must use effective contraception


Biologic therapy:

  • Not specified


  • At least 1 year since prior adjuvant chemotherapy comprising fluorouracil (5-FU) and leucovorin calcium (CF) or 5-FU, CF, and levamisole (LEV)
  • At least 6 months since prior adjuvant chemotherapy comprising 5-FU with or without LEV
  • No other prior chemotherapy
  • No other concurrent chemotherapy

Endocrine therapy:

  • No concurrent hormonal therapy except for nondisease-related conditions, e.g.:
  • Steroids for adrenal failure
  • Insulin for diabetes
  • Intermittent dexamethasone as an antiemetic


  • No prior radiotherapy to the liver


  • See Disease Characteristics

Trial Contact Information

Trial Lead Organizations/Sponsors

Cancer and Leukemia Group B

  • National Cancer Institute
  • Eastern Cooperative Oncology Group
Nancy E. Kemeny, MD, Study Chair
Elin Ruth Sigurdson, Study Chair

Link to the current record.
NLM Identifier NCT00002716 processed this data on April 09, 2015

Note: Information about this trial is from the database. The versions designated for health professionals and patients contain the same text. Minor changes may be made to the record to standardize the names of study sponsors, sites, and contacts. only lists sites that are recruiting patients for active trials, whereas lists all sites for all trials. Questions and comments regarding the presented information should be directed to