Study of XELOX With Cetuximab in Advanced Gastric Cancer

Study Overview
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Brief Summary
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The combination of capecitabine and oxaliplatin as 'backbone' regimen, adding a newer biologic agent, cetuximab, is a reasonable strategy of further chemotherapy development in advanced gastric cancer, which is the investigators study rationale.

Detailed Description
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There is presently no chemotherapy regimen considered to be the global standard of care for patients with AGC, and there is still a need for new agents and/or regimens to improve the efficacy and safety of chemotherapy in advanced stomach cancers. The combination of 5-fluorouracil plus cisplatin (FP) has been widely used for the first-line treatment of advanced gastric cancer in many countries. Randomized phase III trial investigating capecitabine plus cisplatin(XP) versus FP showed XP is at least as good as FP with improved patients' preference. A Phase II study of capecitabine plus oxaliplatin (XELOX) was conducted in our study group.

Official Title
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A Prospective Phase II Study of Cetuximab (Erbitux®) in Combination With XELOX [XELoda® (Capecitabine) and OXaliplatin] in Patients With Advanced Gastric Cancer

Conditions
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Gastric Cancer

Intervention / Treatment
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* Drug: Capecitabine, Oxaliplatin, Cetuximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Having given signed written informed consent Patients must have histologically or cytologically documented stomach adenocarcinoma including adenocarcinoma of the esophagogastric junction. Patients must have unresectable metastatic disease or recurrent disease after curative surgical resection with uni-dimensionally measurable disease according to RECIST (at least longest diameter 1 cm on computed tomography scan, or at least 2 cm on chest x-ray or physical examination Age 18 to 70 years old Estimated life expectancy of more than 3 months ECOG performance status < 2 (See Appendix E) Adequate bone marrow function (WBC>3,000/µL, ANC>1,500/µL, and platelets>100,000/µL, Hb>8g/dl) Adequate kidney function (creatinine<1.5 mg/dL) Adequate liver function [bilirubin< 2.0 mg/dL, transaminases levels<3 times the Upper Normal Value (5 times for patients with liver metastasis)] Prothrombin time not less than 50% of Lower Normal Value No prior chemotherapy No prior radiation therapy Patients must not have psychological, familial, sociological or geographical conditions which do not permit medical follow-up and compliance with this study. Women of childbearing potential must have a negative serum HCG pregnancy test on admission. Men and women of reproductive potential must have agreed to use an effective method of contraception while on treatment and for 6 months after study treatment. Exclusion Criteria: Past or concurrent history of neoplasm other than gastric adenocarcinoma within the last five years, except for curatively treated non-melanoma skin cancer or in situ carcinoma of the cervix uteri. Central nervous system (CNS) metastases. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study treatment start Gastric outlet obstruction, intestinal obstruction and obvious peritoneal seeding. Evidence of serious gastrointestinal bleeding. The patient has bony lesions as the sole evaluable disease. Pregnant or lactating women, women of childbearing potential not employing adequate contraception. Patients with sensory neuropathy (grade> 1 according to NCI CTCAE v. 3.0). Hypersensitivity to any of the study drugs or ingredients. Other serious illness or medical conditions that would not allow study participation in the best interest of the patient as decided by the investigator. Unstable cardiac disease despite treatment, myocardial infarction within 6 months prior to study entry. History of significant neurologic or psychiatric disorders including dementia or seizures. Active uncontrolled infection. Pre-existing clinically significant diarrhea. Unstable diabetes mellitus. Severe hypercalcemia of > 12 mg/dL and uncontrolled with bisphosphonates. Active disseminated intravascular coagulation. Concurrent treatment with corticosteroids (or equivalent) except as use for the prophylactic medication regimen, treatment of acute hypersensitivity reactions or nausea, or unless chronic treatment (initiated > 6 months prior to study entry) at low dose (<20 mg methyl prednisolone or equivalent). Concomitant or administration of any other experimental drug under investigation within 4 weeks before the study. Concomitant or previous hormonal therapy, or immunotherapy.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Capecitbine, oxaliplatin, cetuximab<br>Capecitbine, oxaliplatin and cetuximab every three week; Capecitabine 1,000 mg/m2 was administered twice daily on days 1-14. Oxaliplatin 130 mg/m2 i.v. for 2 h was given on day 1 after cetuximab infusion. Cetuximab at an initial loading dose of 400 mg/m2 i.v. for 2 h and, thereafter, maintenance dose of 250 mg/m2 for 1 h every week. | Drug: Capecitabine, Oxaliplatin, Cetuximab<br>* Xelox(Capecitbine, Oxaliplatin) and Cetuximab every three week; Capecitabine 1,000 mg/m2 was administered twice daily on days 1-14. Oxaliplatin 130 mg/m2 i.v. for 2 h was given on day 1 after cetuximab infusion. Cetuximab at an initial loading dose of 400 mg/m2 i.v. for 2 h and, thereafter, maintenance dose of 250 mg/m2 for 1 h every week.<br>* Other names: xeloda, oxalitin, Erbitux;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate | Tumor response was evaluated every two cycles by CT scans and other indicated methods, and the patients with complete or partial response required a confirmatory response evaluation at least 4 weeks later. Patients without confirmatory evaluation were not regarded as responders. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival |  | 1 year | 
| Overall Survival |  | 1 year | 
| Toxicity Profile | Number of patients who experienced toxicity from study treatment to evaluate the safety and tolerability of XELOX plus Cetuximab | 1 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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gastric cancer, chemotherapy, cetuximab, capecitabine, oxaliplatin