RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies such as cetuximab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Combining chemotherapy with cetuximab may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy plus cetuximab in treating patients who have unresectable liver metastases from colorectal cancer.

Condition	Treatment or Intervention	Phase
liver metastases stage IV colon cancer Stage IV rectal cancer adenocarcinoma of the colon adenocarcinoma of the rectum	Drug: cetuximab  Drug: fluorouracil  Drug: leucovorin calcium  Drug: oxaliplatin  Procedure: antibody therapy  Procedure: biological response modifier therapy  Procedure: chemotherapy  Procedure: monoclonal antibody therapy	Phase II

OBJECTIVES:

• Determine the surgical resectability rate of patients with unresectable hepatic metastases secondary to metastatic colorectal adenocarcinoma expressing epidermal growth factor receptor (EGFR) treated with oxaliplatin, fluorouracil, leucovorin calcium, and cetuximab.
• Determine the response rate and overall survival of patients treated with this regimen.
• Determine, preliminarily, the importance of EGFR levels in predicting response in patients treated with this regimen.
• Determine the quality of life of patients treated with this regimen.
• Determine the toxicity of this regimen in these patients.

OUTLINE: This is a multicenter study.

Patients receive cetuximab IV over 1 hour (except over 2 hours on day 1 of course 1 only) on days 1 and 8. Patients also receive oxaliplatin IV over 2 hours and leucovorin calcium IV over 20 minutes on day 1 and fluorouracil IV continuously on days 1-2. Treatment repeats every 2 weeks in the absence of disease progression or unacceptable toxicity, for a minimum of 12 courses or until deemed to have resectable disease.

Quality of life is assessed at baseline and prior to each treatment course.

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

PROJECTED ACCRUAL: A total of 67-73 patients will be accrued for this study within 3 years.

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

Criteria

DISEASE CHARACTERISTICS:

• History of completely resected primary adenocarcinoma of the colon or rectum
• No gross or microscopic evidence of residual disease
• Liver metastases, meeting 1 of the following criteria:
• Not optimally resectable
• Requires resection of all 3 major hepatic veins, the portal vein bifurcation, or the retrohepatic vena cava
• Includes the main right or main left portal vein and the main hepatic vein of the opposite lobe
• Requires more than a right or left trisegmentectomy
• At least 6 metastatic lesions distributed diffusely in both lobes of the liver
• Tumor expressing epidermal growth factor receptor (EGFR)
• No evidence of extrahepatic metastases by physical examination or x-ray
• No previously resected extrahepatic metastases
• At least 1 measurable lesion at least 20 mm

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• Not specified

Hematopoietic

• Hemoglobin at least 9 g/dL
• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic

• AST no greater than 3 times upper limit of normal (ULN)
• Bilirubin no greater than ULN
• No preexisting chronic hepatic disease (e.g., chronic active hepatitis, cirrhosis) that would preclude surgical resection of metastases

Renal

• Creatinine no greater than 1.5 times ULN

Cardiovascular

• No myocardial infarction within the past 6 months
• No clinical evidence of congestive heart failure
• No significant cardiac disease
• No uncontrolled hypertension
• No unstable angina
• No congestive heart failure
• No uncontrolled arrhythmias

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Adequate oral nutrition with estimated caloric intake of at least 1,500 calories/day
• Able to tolerate major surgery
• No other malignancy within the past 5 years except basal cell or squamous cell skin cancer, carcinoma in situ, or tumors associated with less than 10% probability of death within 5 years of diagnosis
• No severe anorexia or frequent nausea and/or vomiting
• No grade 2 or greater preexisting neuropathy

PRIOR CONCURRENT THERAPY: Biologic therapy

• No colony-stimulating factors within 24 hours of day 1 of each course
• No concurrent immunotherapy

Chemotherapy

• At least 1 year since prior adjuvant systemic fluorouracil with or without levamisole or with or without leucovorin calcium
• No prior systemic chemotherapy for metastatic disease
• No prior chemoembolization for metastatic disease
• No prior hepatic artery infusion chemotherapy for metastatic disease
• No other concurrent chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy to the liver
• No prior radiotherapy to more than 25% of the bone marrow
• At least 12 months since prior adjuvant radiotherapy
• Prior radiofrequency ablation allowed
• No concurrent radiotherapy

Surgery

• See Disease Characteristics
• More than 21 days since prior abdominal exploration (with or without intestinal resection)

Other

• No prior anti-EGFR-directed therapy
• Prior cryotherapy allowed
• No oral cryotherapy on day 1 of each course

Study chairs or principal investigators

Steven R. Alberts, MD,  Study Chair,  Mayo Clinic Cancer Center   

Study ID Numbers:  CDR0000271923; NCCTG-N014A
Record last reviewed:  October 2003
Record first received:  March 6, 2003
ClinicalTrials.gov Identifier:  NCT00056030
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2004-10-20