Leucovorin, Fluorouracil, Cetuximab, and Oxaliplatin in Treating Patients With Stage IV Colorectal Cancer and Liver Metastases That Cannot Be Removed by Surgery

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as leucovorin, fluorouracil, and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving more than one drug (combination chemotherapy) and giving them together with cetuximab may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving leucovorin together with fluorouracil, cetuximab, and oxaliplatin works in treating patients with stage IV colorectal cancer and liver metastases that cannot be removed by surgery.

Detailed Description
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OBJECTIVES: Primary Determine the efficacy of this regimen by the measurement of objective response rate (RECIST criteria). Secondary Determine the toxicity of this regimen. Evaluate the duration of tumor response. Determine the duration and rate of tumor control. Determine the rate of secondary resectability of hepatic metastases. Evaluate progression-free survival Determine rate of progression of the tumor. Determine overall survival. OUTLINE: This is a multicenter study. Patients receive cetuximab IV over 1 hour, leucovorin calcium IV over 2 hours, and fluorouracil IV continuously over 46 hours. Patients also receive oxaliplatin by hepatic arterial infusion over 2 hours. Treatment continues for at least 3 months in the absence of disease progression or unacceptable toxicity.

Official Title
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Phase II Study Evaluating the Effectiveness of the Association of Chemotherapy LV5FU2 Simplified and Cetuximab With Intra-arterial Hepatic Chemotherapy Using Oxaliplatin in Patients With Colorectal Cancer and Nonresectable Hepatic Metastases

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: Histologically confirmed primary cancer of the colon or rectum Isolated hepatic metastases Not amenable to curative resection or requirement for complex and or larger (i.e., > 4 liver segments) liver resection Measurable disease (RECIST criteria) Original tumor must be (or have been) removed PATIENT CHARACTERISTICS: Inclusion criteria: WHO performance status 0-1 Life expectancy > 3 months ANC ≥ 1,500/mm³ Platelet count ≥ 100,000/mm³ Hemoglobin ≥ 9 g/dL Creatinine ≤ 1.5 times normal Bilirubin ≤ 1.5 times upper limit of normal Transaminases ≤ 5 times normal Not pregnant or nursing Fertile patients must use effective contraception Exclusion criteria: Contraindication or allergy grade 3-4 to any components of the study drugs Peripheral neuropathy Intestinal occlusion or subocclusion or prior inflammatory intestinal disease Severe cardiac disease including any of the following: Symptomatic coronary disease Myocardial infarction in the past 6 months New York Heart Association grade II-IV cardiac insufficiency Severe arrhythmia (even if treated) Active or uncontrolled infection Other concurrent serious disorder Severe uncontrolled medical condition Other malignancy within the past 5 years or concurrently except basal cell skin cancer or carcinoma in situ of the cervix Study impossible due to psychological, geographical, or social reasons Prisoners or patients under guardianship PRIOR CONCURRENT THERAPY: Exclusion criteria: Prior chemotherapy except adjuvant chemotherapy comprising fluorouracil, leucovorin calcium, capecitabine, oxaliplatin, irinotecan hydrochloride, and/or bevacizumab (completed > 6 months ago if oxaliplatin- or irinotecan-based) Prior epidermal growth factor (EGF), monoclonal antibody inhibiting transduction of EGF receptor (EGFR), or any other treatment targeting the EGFR Other concurrent anticancer immunotherapy, chemotherapy, or hormone therapy Participation in another study in the past 30 days

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Allocation: Non-Randomized
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: cetuximab|nan|
|Drug: fluorouracil|nan|
|Drug: leucovorin calcium|nan|
|Drug: oxaliplatin|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy: objective tumor response rate (RECIST criteria) |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity as assessed by NCI CTCAE v3.0 |  |  | 
| Duration of response |  |  | 
| Duration and rate of tumor control |  |  | 
| Secondary resectability of hepatic metastases |  |  | 
| Progression-free survival |  |  | 
| Overall survival |  |  | 
| Tumor progression rate |  |  | 

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