Cetuximab and Combination Chemotherapy as First-Line Therapy in Treating Patients With Colorectal Cancer That Has Spread to the Liver and/or Lung

Study Overview
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Brief Summary
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RATIONALE: 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. Drugs used in chemotherapy, such as irinotecan, leucovorin, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving cetuximab together with combination chemotherapy may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving cetuximab together with combination chemotherapy works as first-line therapy in treating patients with colorectal cancer that has spread to the liver and/or lung.

Detailed Description
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OBJECTIVES: Primary Determine the tumor response rate in patients with colorectal cancer and hepatic and/or pulmonary metastases treated with cetuximab and FOLFIRI chemotherapy comprising irinotecan hydrochloride, leucovorin calcium, and fluorouracil as first-line therapy. Secondary Determine the rate of resectability in patients treated with this regimen. Determine the overall and disease-free survival of patients treated with this regimen. Determine the tolerability of this regimen in these patients. OUTLINE: This is a multicenter study. Patients receive cetuximab IV over 60-120 minutes on days 1 and 8. Patients also receive FOLFIRI chemotherapy comprising irinotecan hydrochloride IV over 90 minutes and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV continuously over 48 hours on days 1 and 2. Patients with 7/6 or 7/7 genotypes also receive filgrastim (G-CSF) as primary prophylaxis (patients with 6/6 genotypes receive G-CSF as secondary prophylaxis). Treatment repeats every 2 weeks for up to 8 courses in the absence of disease progression or unacceptable toxicity. Within 6 weeks after the completion of cetuximab and FOLFIRI chemotherapy, patients with responding disease undergo surgical resection of visceral metastases.

Official Title
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Frontline Chemotherapy Reinforced for Cancers of the Colon and Rectum With Potentially Resectable Hepatic and/or Pulmonary Metastases: Association of FOLFIRI and ERBITUX

Conditions
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Colorectal Cancer, Metastatic Cancer

Intervention / Treatment
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* Biological: cetuximab
* Biological: filgrastim
* Drug: fluorouracil
* Drug: irinotecan hydrochloride
* Drug: leucovorin calcium


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed adenocarcinoma of the colon or rectum Must have synchronous or metasynchronous unresectable hepatic metastases Less than 8 hepatic metastases Less than 6 segments of liver involvement with metastases No more than 2 potentially resectable extrahepatic (e.g., pulmonary) metastases Patients with visceral metastases that are potentially resectable after chemotherapy (i.e., tumor regression) are eligible At least 1 measurable metastasis by CT scan or MRI No brain metastases, bone metastases, or carcinomatous meningitis No celiac lymph node involvement or peritoneal cancer PATIENT CHARACTERISTICS: WHO performance status 0-1 Life expectancy > 3 months ANC ≥ 1,500/mm³ Platelet count ≥ 100,000/mm³ PT rate > 70% Bilirubin < 30 μmol/L Creatinine < 130 μmol/L Creatinine clearance > 60 mL/min Not pregnant or nursing No other prior malignancy except basal cell skin cancer or carcinoma in situ of the cervix No severe unstable angina No symptomatic heart failure No other concurrent illness PRIOR CONCURRENT THERAPY: At least 3 months since prior adjuvant anticancer chemotherapy No concurrent participation in another clinical trial

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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: cetuximab, FOLFIRI<br> | Biological: cetuximab<br> <br> Biological: filgrastim<br> <br> Drug: fluorouracil<br> <br> Drug: irinotecan hydrochloride<br> <br> Drug: leucovorin calcium<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor response rate |  | From baseline to end of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of resectability |  | From baseline to end of treatment | 
| Overall and disease-free survival |  | From baseline to end of treatment | 
| Tolerability |  | From baseline to end of treatment | 

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