A Study of Cetuximab(Erbitux) With Cisplatin and Capecitabine(Xeloda)as 1st Line Treatment in the Advanced Gastric Cancer

Study Overview
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Brief Summary
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The purpose of this study is to investigate whether cetuximab (Erbitux®) with cisplatin and capecitabine (Xeloda) as 1st line treatment in the advanced gastric cancer is effective.

Detailed Description
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Gastric cancer remains one of the major causes of cancer deaths around the world, especially in Asia. Previous study of ML17032 has proved that XP(capecitabine plus cisplatin)is effective in advanced gastric cancer, with the overall response rate of 41%, the median PFS of 5.6 month. Recently, the EGFR monoclonal antibody of cetuximab has shown to be successful in treating advanced colorectal cancer with or without chemotherapy. Since EGFR also express in gastric cancer, A single arm, open, multicenter phase II study of cetuximab in combination with cisplatin and capecitabine as first line treatment in patient with advanced gastric cancer.If applicable, the value of mutations in k-ras, b-raf, P53, and EGFR copy number to predict the clinical response to cetuximab in advanced gastric cancer patients will also be accessed.Tumor tissue from study patients will be checked for k-ras, b-raf, and P53 mutation by sequencing and for EGFR copy number by chromogenic in situ hybridization. DNA will be extracted from paraffin-embedded samples.

Conditions
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Gastric Cancer

Intervention / Treatment
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* Drug: cetuximab, cisplatin, capecitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Having signed informed consent Age 18 to 75 years old Histologically confirmed gastric adenocarcinoma Unresectable recurrent or metastatic disease Previous neo-adjuvant or adjuvant treatment for gastric cancer, if applicable, more than 12 months Measurable disease according to the RECIST criteria Karnofsky performance status ≥60 Life expectancy of ≥2 month No prior radiotherapy except radiotherapy at non-target lesion of the study more than 4 weeks ALT and AST<2.5 times ULN (≤5 times ULN in patients with liver metastases) Serum albumin level ≥3.0g/dL Serum AKP < 2.5 times ULN Serum creatinine <1.5mg/dL Bilirubin level < 1.5mg/dL Serum creatinine <1.5 times ULN WBC>3,000/mm3, absolute neutrophil count ≥2000/mm3, platelet>100,000/mm3, Hb>9g/dl Exclusion Criteria: Brain metastasis (known or suspected) Previous systemic therapy for metastatic gastric cancer Inability to take oral medication Previous EGFR pathway-targeting therapy Surgery (excluding diagnostic biopsy) within 4 weeks prior to study entry Heart failure, coronary artery disease, myocardial infarction within the last 6 months Known allergy to any study treatment Pregnancy or lactation period Any investigational agent within the past 28 days Other previous malignancy within 5 year, except non-melanoma skin cancer Previous adjuvant therapy with capecitabine+platinum Pre-existing neuropathy>grade 1 Legal incapacity

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: C225+Chemotherapy<br> | Drug: cetuximab, cisplatin, capecitabine<br>* Product 1: Cetuximab(Erbitux®) Dosing schedule: 400mg/m2 initial dose and then 250mg/m2 ,weekly dose Mode of administration: intravenously Product 2: capecitabine Dosing schedule: 1000mg/m2 bid, days 1-14, every 3 weeks Mode of administration: orally Product 3: cisplatin Dosing schedule: 80mg/m2, day 1 of every 3 weeks Mode of administration: intravenously<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor response rate |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to progression Disease control rate Overall survival K-ras, b-raf, p53 gene mutation and EGFR gene copy number vs. tumor response safety |  | 5 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cetuximab, cisplatin, capecitabine, first line treatment