Pre-operation Chemo and Antibody Therapy Followed by Surgical Resection and Adjuvant Chemoradiation for Gastric Cancer

Study Overview
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Brief Summary
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This study intends to evaluate the feasibility and treatment efficacy of adding an antibody blocking the epidermal growth factor (EGF) pathway to a neoadjuvant approach with proven efficacy developed at New York University.

Detailed Description
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The overall objective of this study is the development of definitive treatments for patients with locally advanced gastric cancer. To this end, this trial is evaluating the feasibility and treatment efficacy of adding an antibody blocking the EGF pathway to a neoadjuvant approach with proven efficacy developed at New York University (NYU). The combination of Irinotecan and Cisplatin has been shown to be synergistic and active against gastric carcinoma. This trial therefore builds upon NYU previous experience with the neoadjuvant administration of Irinotecan combined with Cisplatin as well as the reported enhanced activity of Irinotecan, Cisplatin and External beam radiation when combined with Cetuximab to develop a novel neoadjuvant and adjuvant approach for the treatment of gastric and gastro-esophageal junction (GEJ) cancers. The program includes: 1) systemic combination of Irinotecan, Cisplatin and Cetuximab used as an induction, 2) followed by potentially curative gastrectomy or GEJ resection, and 3) post-operative chemoradiation as reported in the Intergroup study with the addition of Cetuximab.

Official Title
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Neoadjuvant Therapy of Gastric Cancer With Irinotecan, Cisplatin and Cetuximab Followed by Surgical Resection and Adjuvant Chemoradiation

Conditions
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Gastric Cancer, Stomach Cancer

Intervention / Treatment
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* Drug: Cetuximab
* Drug: Irinotecan
* Drug: Cisplatin
* Procedure: Surgery
* Drug: 5-FU
* Radiation: Radiation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have signed an approved informed consent. must have histologically documented untreated gastric/GEJ carcinoma (clinical stage T3 N0 or T4, or any T with N1-N3 M0) Patients with tumor tissue available for assessment of EGF receptor status by immuno-histochemistry (IHC). Patients with Performance Status 0-2. Patients, 18 years and older, must either be not of child bearing potential or have a negative pregnancy test within 7 days of treatment. Patients are considered not of child bearing potential if they are surgically sterile (they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are postmenopausal. Bone marrow function: absolute neutrophil count (ANC) at least 1,500/ul; platelets at least 100,000/ul. Renal function: creatinine not greater than 1.5 x institutional upper limit of normal (ULN). The PT and PTT should be within the range of normal values Hepatic function: bilirubin not greater than 1.5 x ULN; aspartate aminotransferase (AST) not greater than 2.5 x ULN. Exclusion Criteria: Acute hepatitis or known HIV. Active or uncontrolled infection. Significant history of uncontrolled cardiac disease; i.e., uncontrolled hypertension, unstable angina, and congestive heart failure. Prior therapy that affects or targets the EGF pathway. Prior allergic reaction to chimerized or murine monoclonal antibody therapy or documented presence of human anti-mouse antibodies (HAMA). Any concurrent chemotherapy not indicated in the study protocol or any other investigational agent(s).

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Induction/ surgery/ chemoRT<br>Induction treatment (3 weeks/cycle x 4 cycles): Cisplatin and Irinotecan on days 1 and 8; Cetuximab on days 1, 8, and 15. Surgery (starts 3-4 weeks after induction treatment). Chemoradiation treatment (starts 4-6 weeks after surgery): weeks 1-19: Cetuximab on day 1 of every week; week 1: 5-FU and Leucovorin (LV) x 5 days; weeks 2-4: recovery; weeks 5-9: radiation, 150 cGy x 5 fractions/week x 5 weeks; week 5: 5-FU+ LV on days 1-4; week 9: 5-FU+ LV on days 1-3; weeks 14 and 19: 5-FU+LV x 5days | Drug: Cetuximab<br> <br> * Other names: Erbitux;Drug: Irinotecan<br> <br> * Other names: Camptosar;Drug: Cisplatin<br> <br> * Other names: Platinol-AQ;Procedure: Surgery<br> <br> Drug: 5-FU<br> <br> * Other names: Fluorourocil;Radiation: Radiation<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Response Rate of an Induction Regimen Consisting of Irinotecan, Cisplatin and Cetuximab | Clinical response rate is defined as the percentage of patients who responded to the induction regimen. The response is determined based on endoscopic ultrasonography (EUS) staging pre-treatment and post-treatment, CT scans pre- and post- operatively, and initial clinical stage (based on these tests) compared with the pathologic stage. Any down-staging of T or N stage is considered to be a result of induction therapy and counted as a clinical response. | 4 months from the beginning of the induction regimen | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Clearance of Nodal Involvement Among Patients Who Have Received the Induction Therapy | This is defined as the percentage of patients whose nodal involvement of cancer has been cleared based on surgery results. | 4 months from the beginning of the induction treatment | 
| Rate of Potentially Curative Surgery | This is defined as the percentage of patients who underwent curative surgery (surgery to remove all cancerous tissue). | 4 months from the beginning of the induction treatment | 
| Rate of Down-staging From Pre-operative Clinical Staging | This is defined as the percentage of patients who had a reduction from T3/T4 disease. | 4 months from the beginning of the induction treatment | 
| Safety of the Induction Regimen | This describes the number of patients who experienced grade 3 and higher adverse events related to the regimen. | 4 months from the beginning of the induction | 
| Median Overall Survival (Induction Treatment and Curative Surgery) | This is the length of time from the start of treatment that half of the patients are still alive. | up to 5 years | 
| Median Overall Survival (Adjuvant Therpary) | This is the length of time from the start of treatment that half of the patients are still alive. | up to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stomach cancer, biologics, antibody, chemotherapy, chemoradiation, adjuvant therapy, neoadjuvant therapy, epidermal growth factor receptor, combination therapy