RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Hepatic arterial infusion uses a catheter to deliver chemotherapy directly to the liver. Chemoprotective drugs such as dexamethasone may protect normal cells from the side effects of chemotherapy. Combining more than one chemotherapy drug and giving them after surgery may kill any remaining tumor cells.

PURPOSE: Phase I trial to study the effectiveness of combining adjuvant hepatic arterial infusion with combination chemotherapy in treating patients who have resectable hepatic (liver) metastases from colorectal cancer.

Condition	Treatment or Intervention	Phase
Colon Cancer liver metastases Rectal Cancer	Drug: dexamethasone  Drug: floxuridine  Drug: fluorouracil  Drug: leucovorin calcium  Drug: oxaliplatin  Procedure: adjuvant therapy  Procedure: chemoprotection  Procedure: chemotherapy  Procedure: conventional surgery  Procedure: hepatic arterial infusion  Procedure: supportive care/therapy  Procedure: surgery	Phase I

Further Study Details: 

OBJECTIVES:

• Determine the maximum tolerated dose of intravenous oxaliplatin and fluorouracil when administered with leucovorin calcium in combination with hepatic arterial infusion of floxuridine and dexamethasone in patients with resectable hepatic metastases secondary to colorectal adenocarcinoma.
• Correlate thymidylate synthase, dihydropyrimidine dehydrogenase, and excision repair cross-complementing genes in normal and tumor liver tissue with survival and recurrence in patients treated with this regimen.

OUTLINE: This is a dose-escalation study of oxaliplatin and fluorouracil.

Patients undergo surgery for resection of the liver and placement of the hepatic artery pump.

• Hepatic arterial infusion (HAI) therapy: Approximately 4 weeks after surgery, patients receive HAI therapy comprising floxuridine and dexamethasone on day 1.
• Patients receive oxaliplatin IV and leucovorin calcium IV over 120 minutes and fluorouracil IV bolus (followed by a 48-hour infusion of fluorouracil) on days 15 and 29. Cohorts of 3-6 patients receive escalating doses of oxaliplatin and fluorouracil until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Treatment repeats every 36 days for up to 6 courses in the absence of disease recurrence or unacceptable toxicity.

Patients are followed every 3 months after the completion of treatment.

PROJECTED ACCRUAL: A total of 2-54 patients will be accrued for this study within 12-16 months.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed colorectal adenocarcinoma metastatic to the liver
• No clinical or radiographic evidence of extrahepatic disease
• Potentially completely resectable hepatic metastases without current evidence of other metastatic disease
• No ascites

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• Karnofsky 60-100%

Life expectancy

• Not specified

Hematopoietic

• WBC at least 3,000/mm^3
• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic

• Bilirubin no greater than 1.5 mg/dL
• No hepatic encephalopathy

Renal

• Not specified

Other

• Not pregnant or nursing
• Negative pregnancy test
• No active infection

PRIOR CONCURRENT THERAPY: Biologic therapy

• Not specified

Chemotherapy

• At least 3 weeks since prior chemotherapy
• No prior oxaliplatin
• No prior cisplatin
• No prior hepatic arterial infusion of floxuridine

Endocrine therapy

• Not specified

Radiotherapy

• At least 4 weeks since prior radiotherapy to the pelvis
• No prior radiotherapy to the liver

Surgery

• Not specified

New York
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States; Recruiting

Study chairs or principal investigators

Nancy E. Kemeny, MD,  Study Chair,  Memorial Sloan-Kettering Cancer Center   

Study ID Numbers:  CDR0000298988; MSKCC-03005; NCT00059930
Record last reviewed:  October 2004
Last Updated:  December 6, 2004
Record first received:  May 6, 2003
ClinicalTrials.gov Identifier:  NCT00059930
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08