Oxaliplatin, Capecitabine, and Radiation Therapy in Patients Undergoing Surgery for Stage II, III, IV Esophageal Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as oxaliplatin and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving chemotherapy together with radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. PURPOSE: This phase II trial is studying how well giving oxaliplatin and capecitabine together with radiation therapy works in treating patients undergoing surgery for stage II, stage III, or stage IV esophageal cancer.

Detailed Description
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OBJECTIVES: Primary Determine the complete pathologic response (complete response [CR]) rate in patients with stage II-IVA esophageal cancer treated with neoadjuvant oxaliplatin, capecitabine, and radiotherapy. Secondary Determine the clinical efficacy and toxicity of this regimen in these patients. Determine the quality of life of patients treated with this regimen. Identify basal expression and changes in gene expression that relate to CR, relapse, and survival of patients treated with this regimen. OUTLINE: Neoadjuvant chemoradiotherapy: Patients receive oxaliplatin IV over 2 hours on days 1, 15, and 29 (weeks 1, 3, and 5). Patients also undergo radiotherapy on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-38 and receive oral or enteral capecitabine twice daily on the same days they undergo radiotherapy. Surgery: At 4-6 weeks after completion of neoadjuvant chemoradiotherapy, patients who are eligible undergo esophagectomy. Adjuvant chemotherapy: Beginning 4-6 weeks after surgery, patients receive oxaliplatin IV over 2 hours on days 1, 15, and 29 and oral or enteral capecitabine twice daily on days 1-5, 8-12, 15-19, 22-26, and 29. Treatment repeats approximately every 14 days for up to 2 courses in the absence of disease progression or unacceptable toxicity. Patients undergo tumor biopsies periodically. Collected samples are analyzed by gene expression studies, microarray analysis, and real-time quantitative reverse transcriptase-PCR to identify basal expression and changes in gene expression. Quality of life is assessed periodically. After completion of study treatment, patients are followed periodically for 5 years. PROJECTED ACCRUAL: A total of 36 patients will be accrued for this study.

Official Title
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Phase II Study of Capecitabine in Combination With Oxaliplatin and Radiotherapy for Esophageal and Gastroesophageal Junction Cancer

Conditions
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Esophageal Cancer

Intervention / Treatment
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* Drug: capecitabine
* Drug: oxaliplatin
* Genetic: gene expression analysis
* Genetic: microarray analysis
* Genetic: reverse transcriptase-polymerase chain reaction
* Procedure: adjuvant therapy
* Procedure: biopsy
* Procedure: conventional surgery
* Procedure: neoadjuvant therapy
* Procedure: quality-of-life assessment
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of squamous cell carcinoma of the esophagus or adenocarcinoma of the esophagus Stage II-IVA disease as determined by clinical staging, including endoscopy and CT scan with or without endoscopic ultrasound Bulk of gastroesophageal junction tumor should be in the esophagus Bronchoscopy with biopsy and cytology required if primary esophageal cancer is < 26 cm from incisors No known brain metastases PATIENT CHARACTERISTICS: ECOG performance status 0-1 Life expectancy > 4 months WBC > 4,000/mm³ ANC > 1,500/mm³ Platelet count > 100,000/mm³ Hemoglobin > 9 g/dL Bilirubin normal Creatinine normal AST < 2.5 times upper limit of normal (ULN) Alkaline phosphatase ≤ 3 times ULN Able to take oral medication or undergo enteral administration of medication No peripheral neuropathy ≥ grade 2 Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 90 days after completion of study treatment No hypersensitivity to platinum compounds, fluoropyrimidines, or antiemetics administered in combination with protocol-directed chemotherapy No concurrent uncontrolled illness, including, but not limited to, any of the following: Ongoing or active infection Symptomatic congestive heart failure Unstable angina pectoris Cardiac arrhythmia Psychiatric illness or social situation that would preclude study compliance No history of second malignancy except for curatively treated carcinoma in situ of the cervix or nonmelanoma skin cancer Other cured tumors allowed at discretion of the principal investigator No known HIV or hepatitis B or C (active and/or previously treated) PRIOR CONCURRENT THERAPY: No prior therapy for esophageal cancer No other concurrent investigational agents

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: Chemo<br>Oxaliplatin 85 mg/m2 will be administered IV on days 1, 15 and 29. Capecitabine 1250 mg/m2 will be administered in 2 divided daily doses P0 or via enteral tube, on radiation days only (Monday- Friday/ weekly). Capecitabine will be continued until the final dose of radiotherapy | Drug: capecitabine<br>* Oral<br>Drug: oxaliplatin<br>* IV<br>Genetic: gene expression analysis<br>* Correlative Study<br>Genetic: microarray analysis<br>* Correlative Study<br>Genetic: reverse transcriptase-polymerase chain reaction<br>* Correlative Study<br>Procedure: adjuvant therapy<br>* Metastatic growth control<br>Procedure: biopsy<br>* Examination of tissue type<br>Procedure: conventional surgery<br>* Tissue removal<br>Procedure: neoadjuvant therapy<br>* Tumor shrinkage<br>Procedure: quality-of-life assessment<br>* Correlative Study<br>Radiation: radiation therapy<br>* Undergoing radiation therapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Response |  | 5.5 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (Complete and Partial Response) as Measured by RECIST Criteria After Course 1 |  | 5.5 weeks | 
| Median Time to Progression |  | 5.5 weeks | 
| Quality of Life Improved Rate |  | 5.5 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adenocarcinoma of the esophagus, squamous cell carcinoma of the esophagus, stage II esophageal cancer, stage III esophageal cancer, stage IV esophageal cancer