Capecitabine and Oxaliplatin With or Without Cetuximab in Treating Patients With Metastatic Colorectal Cancer 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 capecitabine and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. 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. Cetuximab may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether giving capecitabine and oxaliplatin together with cetuximab is more effective than capecitabine and oxaliplatin in treating colorectal cancer. PURPOSE: This randomized phase II trial is studying how well giving capecitabine and oxaliplatin together with cetuximab works compared to capecitabine and oxaliplatin in treating patients with metastatic colorectal cancer that cannot be removed by surgery.

Detailed Description
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OBJECTIVES: Compare the efficacy of capecitabine and oxaliplatin with vs without cetuximab in patients with epidermal growth factor receptor-positive metastatic unresectable colorectal cancer. Compare the objective response (complete and partial response) in patients treated with these regimens. Secondary Compare the safety of these regimens in these patients. Compare the clinical benefit (complete response, partial response, or stable disease for at least 18 weeks) in patients treated with these regimens. Compare overall survival, time to progression, and time to treatment failure in patients treated with these regimens. OUTLINE: This is a multicenter, randomized study. Patients are stratified according to performance status (0 vs 1), type of metastases (synchronous vs metachronous), prior adjuvant chemotherapy (yes vs no), and participating center. Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive oral capecitabine twice daily on days 1-15 and oxaliplatin IV over 2 hours on day 1. Arm II: Patients receive capecitabine and oxaliplatin as in arm I and cetuximab IV over 1-2 hours on days 1 and 8. In both arms, courses repeat every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients will be followed every 3 months for 1 year and then every 6 months thereafter. PROJECTED ACCRUAL: A total of 74 patients (37 per treatment arm) will be accrued for this study within 1.5 years.

Official Title
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Capecitabine and Oxaliplatin Alone or in Combination With Cetuximab as First-Line Treatment for Metastatic EGFR-Positive Colorectal Cancer, A Randomized Multicenter Phase II Trial

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: capecitabine and oxaliplatin + cetuximab
* Drug: capecitabine and oxaliplatin


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed metastatic colorectal cancer Unresectable disease Primary tumor or metastases must be epidermal growth factor receptor-positive by immunohistochemistry Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by CT scan Measurable lesion must not be in a previously irradiated area No prior or current CNS metastases PATIENT CHARACTERISTICS: Age 18 and over Performance status WHO 0-1 Life expectancy Not specified Hematopoietic Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hepatic Bilirubin normal Renal Creatinine clearance > 50 ml/min Cardiovascular No New York Heart Association class III or IV congestive heart failure No symptomatic coronary artery disease No uncontrolled cardiac arrhythmia No myocardial infarction within the past 12 months No other significant cardiac disease Other Not pregnant or nursing Fertile patients must use effective contraception during and for 12 months after study participation Negative pregnancy test No peripheral neuropathy of any origin > grade 1 (e.g., alcohol or diabetes) No nausea, vomiting, or malabsorption syndrome that would preclude ingestion or absorption of oral medication No severe reaction attributed to fluoropyrimidine therapy No known hypersensitivity to fluorouracil or any other component of the trial drugs No known dihydropyrimidine dehydrogenase deficiency No other medical condition (e.g., uncontrolled diabetes or active autoimmune disease), geographical situation, or psychiatric disorder that would preclude study compliance No other malignancy within the past 5 years except adequately treated carcinoma in situ of the cervix or localized nonmelanoma skin cancer PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy No prior chemotherapy for advanced or metastatic cancer At least 6 months since prior adjuvant chemotherapy Endocrine therapy Not specified Radiotherapy Not specified Surgery Not specified Other At least 30 days since prior experimental drugs No other concurrent experimental drugs No concurrent drugs that are contraindicated for use with the trial drugs No other concurrent anticancer therapy No concurrent sorivudine or any of its chemically-related analogues (e.g., lamivudine)

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: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm I<br>Patients receive oral capecitabine twice daily on days 1-15 and oxaliplatin IV over 2 hours on day 1. | Drug: capecitabine and oxaliplatin<br>* capecitabine and oxaliplatin without cetuximab<br>|
| Active Comparator: Arm II<br>Patients receive capecitabine and oxaliplatin as in arm I and cetuximab IV over 1-2 hours on days 1 and 8 | Drug: capecitabine and oxaliplatin + cetuximab<br>* cetuximab<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response (complete response [CR] and partial response [PR]) measured after completion of study treatment |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical benefit (CR, PR, and stable disease [SD]) measured at 18 weeks after randomization |  |  | 
| Time to progression |  |  | 
| Overall survival |  |  | 
| Time to treatment failure measured after completion of study treatment |  |  | 
| Adverse drug reactions measured after completion of study treatment |  |  | 

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