Chemotherapy, Radiation Therapy and Immunotherapy Prior to Surgery in Operable Esophageal Cancer

Study Overview
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Brief Summary
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The purpose of this study is to see if adding two targeted drugs (bevacizumab and erlotinib) further improves the response to chemotherapy (5-FU, paclitaxel, carboplatin) and radiation therapy in patients with operable esophageal cancer. Side effects (toxicity) information will also be collected.

Detailed Description
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Surgical removal has been the standard treatment for operable esophageal cancer. However, recent studies have shown improved results when patients receive a short course of chemotherapy and radiation therapy prior to surgery. Prior to surgery study treatment will be given over a 6 weeks (Days 1-42) period. Beginning Day 1 and continuing through Day 35 patients will receive a continuous infusion of 5-FU by vein. A small portable pump will be used to administer this drug into a tube that has been surgically inserted into the patient's vein. On Day 1 and 22 patients will also receive the drugs paclitaxel, carboplatin and bevacizumab by vein. Erlotinib is given by mouth beginning on Day 1 and continuing through Day 45. Patients will receive radiation therapy daily, Monday through Friday, beginning Day 1-35 (approximately 5 weeks). Surgery will be performed approximately 12-14 weeks after beginning this combined treatment.

Official Title
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A Phase II Trial of Preoperative Concurrent Chemotherapy/Radiation Therapy Plus Bevacizumab/Erlotinib in the Treatment of Localized Esophageal Cancer

Conditions
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Esophageal Cancer

Intervention / Treatment
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* Drug: Erlotinib
* Drug: Bevacizumab
* Drug: Paclitaxel
* Drug: Carboplatin
* Drug: 5-FU
* Procedure: Radiation therapy
* Procedure: Surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinically confirmed esophageal or gastroesophageal junction cancer stage I, II or III No prior treatment for esophageal cancer Must be surgical candidate based on stage and location of disease Measurable or evaluable disease Able to be up and perform self care Adequate liver, renal function and bone marrow function Patients will have to have a central venous access device placed Able to give written informed consent. Age 18 or older Exclusion Criteria: Stage IV disease Prior cancer treatment for advanced cancer in the last 5 years Pregnant or lactating women History of stroke, transient ischemic attacks, or acute MI within the past 6 months or any other serious cardiovascular disease History of neurological disease Recent history of blood in the sputum or vomitus Non-healing wounds, ulcer or long bone fractures History of bleeding problems or coagulation problems History of abdominal fistula, gi perforation or intrabdominal abscess within 6 months History of uncontrolled hypertension Please note: There are additional inclusion/exclusion criteria. The study center will determine if you meet all of the criteria. If you do not qualify for the trial, study personnel will explain the reasons. If you do qualify, study personnel will explain the trial in detail and answer any questions you may have. You can then decide if you wish to participate.

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: Treatment<br>Prior to surgery study treatment will be given over a 6 weeks (Days 1-42) period. Beginning Day 1 and continuing through Day 35 patients will receive a continuous infusion of 5-FU by vein. A small portable pump will be used to administer this drug into a tube that has been surgically inserted into the patient's vein. On Day 1 and 22 patients will also receive the drugs paclitaxel, carboplatin and bevacizumab by vein. Erlotinib is given by mouth beginning on Day 1 and continuing through Day 45. Patients will receive radiation therapy daily, Monday through Friday, beginning Day 1-35 (approximately 5 weeks). Surgery will be performed approximately 12-14 weeks after beginning this combined treatment. | Drug: Erlotinib<br>* Erlotinib<br>* Other names: Tarceva;Drug: Bevacizumab<br>* Bevacizumab<br>* Other names: Avastin;Drug: Paclitaxel<br>* Paclitaxel<br>* Other names: Taxol;Drug: Carboplatin<br>* Carboplatin<br>* Other names: Paraplatin;Drug: 5-FU<br>* 5-FU<br>* Other names: Fluorouracil;Procedure: Radiation therapy<br>* Radiation therapy<br>Procedure: Surgery<br>* Surgery<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathologic Complete Response (pCR) Rate | pCR was defined as no residual viable cancer found at the primary site or regional lymph nodes upon pathologic review of the surgical specimen for patients who went to surgical resection. | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Overall Survival (OS) is defined as the time interval from the start of treatment until death. Patients who remained alive were censored at the date of their last tumor assessment. | 32 months | 
| Progression-Free Survival | Progression-free survival (PFS) was defined as the interval from the date of first treatment until the date of disease progression or death, whichever occurred first. Patients who did not progress were censored at the date of their last tumor assessment. | 36 months |