Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

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 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

OBJECTIVES:

• 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

DISEASE CHARACTERISTICS:

• 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

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• See Disease Characteristics

• Bilirubin no greater than 2 times normal

Renal:

• Not specified

Other:

• 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

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• 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

Radiotherapy:

• No prior radiotherapy to the liver

Surgery:

• See Disease Characteristics

Trial Contact Information

Trial Lead Organizations/Sponsors

Cancer and Leukemia Group B

Nancy E. Kemeny

Study Chair

Elin Ruth Sigurdson

Study Chair

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00002716
Information obtained from ClinicalTrials.gov on February 18, 2013

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