Phase II Trial for Patients With Loco-Regional Esophageal Carcinoma

Study Overview
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Brief Summary
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The purpose of this study is to determine whether bevacizumab can improve the outcome of treatment for patients with esophageal cancer whose disease is confined to the esophagus or the closely surrounding lymph nodes.

Detailed Description
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Standard treatment is pre-operative chemotherapy and radiation, followed by surgery. In this study, bevacizumab will be added to the pre-operative chemotherapy and radiation, and then bevacizumab will also be administered for a year after surgery. Bevacizumab is a humanized monoclonal antibody (a type of protein that is normally made by the immune system to help defend the body from infection and cancer) produced by Genentech, Inc. using recombinant DNA technology. Bevacizumab has been approved by the FDA for the treatment of metastatic colorectal cancer in combination with chemotherapy. Bevacizumab is experimental in the treatment of esophageal cancer and has not been approved by the FDA for the treatment of esophageal cancer. Bevacizumab is an antibody directed against vascular endothelial growth factor, or VEGF. VEGF is a growth factor with a well defined role in normal and abnormal blood vessel formation. It is present in a wide variety of normal tissues, but is produced in excess by most solid cancers (tumors). In the setting of cancer, VEGF promotes the growth of blood vessels that bring nutrients to tumor cells. In studies with laboratory animals, bevacizumab inhibits the growth of several different types of human cancer cells, including colon cancer cells, by blocking the effects of VEGF. By blocking VEGF, your doctors hope that bevacizumab may decrease blood supply to the tumor, and therefore decrease the ability of the tumor to grow and come back after chemotherapy, radiation, and surgery.

Official Title
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Phase II Trial of Pre-Operative Chemoradiation Plus Bevacizumab, Followed by Surgery, and Post-Operative Adjuvant Bevacizumab for Patients With Loco-Regional Esophageal Carcinoma

Conditions
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Loco-regional Esophageal Cancer

Intervention / Treatment
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* Drug: Bevacizumab
* Drug: Paclitaxel
* Drug: Cisplatin
* Drug: 5-Fluorouracil
* Radiation: Radiation Therapy
* Procedure: Esophagectomy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: No prior treatment for esophageal cancer No prior radiation to the chest or upper abdominal area No prior treatment with an EGFR inhibitor or an anti-angiogenic agent Disease should be limited to the esophagus and regional lymph nodes - Exclusion Criteria: History of stroke History of heart attack Inadequately controlled high blood pressure

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bevacizumab<br> | Drug: Bevacizumab<br>* Pre-Operative Treatment: Bevacizumab will be given over 60-90 minutes through an I.V. catheter on days # 2 and 16. Post-Operative Treatment:Bevacizumab given over 60-90 minutes through an I.V. catheter every 21 days for 12 months, starting 6-8 weeks after surgery.<br>* Other names: Avastin;Drug: Paclitaxel<br>* Pre-Operative Chemotherapy treatment: Paclitaxel 45 mg/m2 will be administered as a 1-hour intravenous infusion on days #2, 9, 16, 23, and 30. It will be given before cisplatin administration.<br>Drug: Cisplatin<br>* Pre-Operative Chemotherapy Treatment: Cisplatin 30 mg/m2 over 1 hour on days #2, 9, 16, 23, and 30. It will be given after paclitaxel.<br>Drug: 5-Fluorouracil<br>* Pre-Operative Chemotherapy Treatment: 5-Fluorouracil at 200 mg/m2/day will be given as a continuous intravenous infusion on days #2-33.<br>Radiation: Radiation Therapy<br>* Pre-Operative Treatment: Radiotherapy will be given Monday through Friday five days a week on days 1-5, 8-12, 15-19, 22-26, and 29-33. Radiotherapy will be administered using MV x-rays. CT scans, the barium swallow, the endoscopy and endoscopic ultrasound reports and PET scans should be used for tumor definition. Post-Operative Radiotherapy: In the event that gross residual disease is left behind at the time of surgery or the patient is found to have a microscopic positive deep or gastric margin following surgery, additional treatment with radiation therapy will be considered.<br>Procedure: Esophagectomy<br>* Transhiatal esophagectomy performed on approximately Day #57 (6 weeks after last dose of bevacizumab.)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Free Survival Time | The primary outcome that will be measured is the length of time that patients are alive without recurrence of cancer following this therapy. | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Number of Patients Cancer Free at the Time of Surgery | Determination of whether the pre-operative treatment can eliminate all the cancer cells at the time of surgery. | 1 year | 
| The Proportion of Toxicities Experienced by Participants | To assess the toxicity of this regimen. | Every three weeks for one year |