RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Giving the drugs in different combinations and different ways may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of hepatic arterial infusion plus chemotherapy in treating patients who have colorectal cancer metastatic to the liver.

Condition	Treatment or Intervention	Phase
Colon Cancer liver metastases Rectal Cancer	Drug: capecitabine  Drug: dexamethasone  Drug: floxuridine  Drug: oxaliplatin  Procedure: adjuvant therapy  Procedure: chemotherapy	Phase II

Further Study Details: 

OBJECTIVES:

• Determine the safety and toxicity of hepatic arterial infusion with floxuridine and dexamethasone followed by systemic therapy with oxaliplatin and capecitabine in patients with surgically resected liver metastases from primary colorectal carcinoma.
• Determine the 2-year survival rate of patients treated with this regimen.
• Determine the 2-year recurrence rate and time to recurrence in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive floxuridine and dexamethasone intra-arterially continuously on days 1-14, oxaliplatin IV over 2 hours on day 22, and oral capecitabine twice daily on days 22-35. Treatment repeats every 6 weeks for 4 courses in the absence of disease recurrence or unacceptable toxicity. After completion of the fourth course, patients receive oxaliplatin IV over 2 hours on day 1 and oral capecitabine twice daily on days 1-14. Treatment repeats every 3 weeks for 2 courses in the absence of disease recurrence or unacceptable toxicity.

Patients are followed every 3 months for 1 year and then every 6 months for 2.5 years.

PROJECTED ACCRUAL: A total of 15-75 patients will be accrued for this study within 9 months-3.25 years.

Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed colorectal adenocarcinoma metastatic to the liver
• No extrahepatic metastases
• Prior complete surgical resection of hepatic metastases (at least 1 lesion) within the past 21-56 days
• Negative surgical margins unless surrounding normal liver tissue was ablated during surgery
• Radiofrequency ablation may be used as adjunct to surgical resection but not as primary treatment
• No prior operative ultrasound during resection of hepatic metastases
• Prior complete surgical resection of carcinoma of colon or rectum (must appear completely resectable in case of synchronous lesions)

PATIENT CHARACTERISTICS: Age:

• Not specified

Performance status:

• ECOG 0-1

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count at least 1,200/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• AST no greater than 2.5 times ULN
• Alkaline phosphatase no greater than 2.5 times ULN
• No pre-existing chronic hepatic disease (chronic active hepatitis or cirrhosis)

Renal:

• Creatinine no greater than ULN OR
• Creatinine clearance greater than 60 mL/min

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Adequate oral nutrition (at least 1,500 calories/day)
• Able to withstand major operative procedure
• No dehydration
• No severe anorexia
• No frequent nausea or vomiting
• No prior or concurrent malignancy within the past 5 years except basal cell or squamous cell skin cancer or carcinoma in situ of any organ
• No prior or concurrent malignancy associated with more than 10% probability of death from malignant disease within 5 years of diagnosis

PRIOR CONCURRENT THERAPY: Biologic therapy:

• No concurrent immunotherapy
• No concurrent colony-stimulating factors during the first course of study therapy

Chemotherapy:

• No more than 1 prior adjuvant systemic fluorouracil (5-FU) regimen with or without levamisole, leucovorin calcium, or irinotecan
• One prior 5-FU-based regimen as neoadjuvant treatment for rectal cancer is allowed
• No prior hepatic artery infusion therapy with 5-FU or floxuridine
• No prior systemic chemotherapy for metastatic disease
• No other concurrent chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• No concurrent radiotherapy

Surgery:

• See Disease Characteristics

Other:

• No prior or concurrent sorivudine or brivudine

Arizona
      CCOP - Mayo Clinic Scottsdale Oncology Program, Scottsdale,  Arizona,  85259-5404,  United States
Florida
      Mayo Clinic - Jacksonville, Jacksonville,  Florida,  32224,  United States
Illinois
      CCOP - Carle Cancer Center, Urbana,  Illinois,  61801,  United States
      CCOP - Illinois Oncology Research Association, Peoria,  Illinois,  61602,  United States
Iowa
      CCOP - Cedar Rapids Oncology Project, Cedar Rapids,  Iowa,  52403-1206,  United States
      CCOP - Iowa Oncology Research Association, Des Moines,  Iowa,  50309-1016,  United States
      Siouxland Hematology-Oncology, Sioux City,  Iowa,  51101-1733,  United States
Louisiana
      CCOP - Ochsner, New Orleans,  Louisiana,  70121,  United States
Minnesota
      CCOP - Metro-Minnesota, Saint Louis Park,  Minnesota,  55416,  United States
      Mayo Clinic Cancer Center, Rochester,  Minnesota,  55905,  United States
North Dakota
      Altru Cancer Center, Grand Forks,  North Dakota,  58201,  United States
      Medcenter One Health System, Bismarck,  North Dakota,  58501-5505,  United States
Ohio
      CCOP - Dayton, Dayton,  Ohio,  45429,  United States
      CCOP - Toledo Community Hospital, Toledo,  Ohio,  43623-3456,  United States
Pennsylvania
      Allegheny General Hospital, Pittsburgh,  Pennsylvania,  15212-4772,  United States
      CCOP - Geisinger Clinic and Medical Center, Danville,  Pennsylvania,  17822-2001,  United States
South Carolina
      CCOP - Upstate Carolina, Spartanburg,  South Carolina,  29303,  United States
South Dakota
      CCOP - Sioux Community Cancer Consortium, Sioux Falls,  South Dakota,  57104,  United States
Wisconsin
      Medical College of Wisconsin Cancer Center, Milwaukee,  Wisconsin,  53226,  United States

Study chairs or principal investigators

Steven R. Alberts, MD,  Study Chair,  Mayo Clinic Cancer Center   
Michael J. O'Connell, MD,  Study Chair,  Allegheny General Hospital   

Study ID Numbers:  CDR0000069011; NCCTG-N9945; NSABP-CI-66
Record last reviewed:  March 2005
Last Updated:  March 10, 2005
Record first received:  November 9, 2001
ClinicalTrials.gov Identifier:  NCT00026234
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08