Combination Chemotherapy Plus Cetuximab in Treating Patients With Liver Metastases From Colorectal Cancer

Study Overview
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Brief Summary
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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: This phase II trial is studying how well giving combination chemotherapy together with cetuximab works in treating patients with unresectable liver metastases from colorectal cancer.

Detailed Description
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OBJECTIVES: Determine the surgical resectability rate of patients with unresectable hepatic metastases secondary to metastatic colorectal adenocarcinoma treated with oxaliplatin, fluorouracil, leucovorin calcium, and cetuximab. Determine the response rate and overall survival of 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 (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 2 hours 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 4 years.

Official Title
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A Phase II Study Of Oxaliplatin (OXAL), 5-Fluorouracil (5-FU), Leucovorin (CF), and Cetuximab (C225) For Patients With Unresectable Hepatic Metastases From Metastatic Adenocarcinoma Of The Colon Or Rectum

Conditions
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Colorectal Cancer, Metastatic Cancer

Intervention / Treatment
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* Biological: cetuximab
* Drug: fluorouracil
* Drug: leucovorin calcium
* Drug: oxaliplatin


Participation Criteria
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Eligibility Criteria
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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 Measurable disease At least 1 measurable lesion ≥ 20 mm No evidence of extrahepatic metastases by physical examination or x-ray No previously resected extrahepatic metastases PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 0-1 Life expectancy Not specified Hematopoietic Hemoglobin ≥ 9 g/dL Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hepatic AST ≤ 3 times upper limit of normal (ULN) Bilirubin ≤ ULN No preexisting chronic hepatic disease (e.g., chronic active hepatitis, cirrhosis) that would preclude surgical resection of metastases Renal Creatinine ≤ 1.5 times ULN Cardiovascular No myocardial infarction within the past 6 months No clinical evidence of congestive heart failure No New York Heart Association class III-IV heart disease No significant cardiac disease No uncontrolled hypertension No unstable angina No congestive heart failure No uncontrolled arrhythmias Gastrointestinal Adequate oral nutrition with estimated caloric intake of ≥ 1,500 calories/day No severe anorexia or frequent nausea and/or vomiting No history of gastrointestinal bleeding that has not been appropriately addressed Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Able to tolerate major surgery No prior allergic reaction or known sensitivity to chimerized or murine monoclonal antibody therapy No documented presence of human anti-mouse antibodies No known allergy to other platinum compounds 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 preexisting neuropathy ≥ grade 2 No symptomatic pulmonary fibrosis or interstitial pneumonitis No uncontrolled bacterial or viral infection HIV negative No fungal infection 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 oxaliplatin 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 At least 12 months since prior adjuvant radiotherapy Prior radiofrequency ablation allowed No prior radiotherapy to the liver No prior radiotherapy to more than 25% of the bone marrow 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: cetuximab + oxaliplatin + leucovorin + fluorouracil<br>Patients receive cetuximab IV over 1 hour (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 2 hours 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. | Biological: cetuximab<br> <br> Drug: fluorouracil<br> <br> Drug: leucovorin calcium<br> <br> Drug: oxaliplatin<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Surgical resectability rate as assessed by surgical resection of liver metastases |  | Up to 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate as measured by RECIST criteria every 6 weeks |  | Up to 4 years | 
| Overall survival |  | Up to 4 years | 
| Quality of life as assessed by UNISCALE and Symptom Distress Scale every 6 weeks |  | Up to 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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liver metastases, stage IV colon cancer, stage IV rectal cancer, adenocarcinoma of the colon, adenocarcinoma of the rectum