Clinical Trials

To assess the effect of ablation therapy on Barrett's esophagus. Proposal Ablation therapy is an FDA approved treatment to decrease cancer risk in Barrett's esophagus mucosa. This is being performed in our Barrett's Esophagus Unit on a regular basis. However, the longterm outcomes of this therapy is not established and there are patients who have been treated who later re-develop Barrett's mucosa. This study will allow us store tissue samples that can later be used to assess the effect of ablative therapy on Barrett's esophagus.

The primary objective of this clinical trial is to evaluate the performance of the Nvision Volumetric Laser Endomicroscopy (VLE) system to visualize subsurface tissue in subjects undergoing esophagogastroduodenoscopy (EGD) and to identify work-flow and training implications for introducing this new imaging modality.

This research study is trying to determine whether Barrett's esophagus and associated esophageal cancers, specifically esophageal adenocarcinoma are inherited in certain families. Persons who are affected with Barrett's esophagus or esophageal cancer (adenocarcinoma type) are asked to complete a questionnaire that determines their habits and asks a detailed family history. Family members of patients seen at University Hospitals of Cleveland and the Cleveland Clinic are also being recruited for screening tests of their esophagus. The investigators plan to eventually screen family members at all participating institutions. This research will eventually lead to the identification of inherited genetic changes that cause Barrett's esophagus and esophageal cancer. It will help the investigators develop better methods for preventing or identifying esophageal cancer at an early curable stage.

Barrett's esophagus (BE) is a complication of gastroesophageal reflux disease in which the normal squamous lining of the esophagus is replaced by specialized columnar epithelium.1 Approximately 5%-10% of patients diagnosed with BE are thought to be at risk of developing esophageal adenocarcinoma.2 Patients with high-grade dysplasia (HGD) on biopsy are at the greatest cancer risk³. EMR is being performed clinically in our Barrett's Esophagus Unit on a regular basis during endoscopy for patients with Barrett's Esophagus and/or early esophageal adenocarcinoma. There are two predominant endoscopic mucosal resection (EMR) techniques exist using FDA approved devices - the EMR cap method using a transparent cap/snare combination and the endoscopic variceal ligation method using a band ligator/snare combination to resect tissue.

PRIMARY OBJECTIVES:

     l. To determine if trastuzumab increases disease-free survival when combined with trimodality treatment (radiation plus chemotherapy followed by surgery) for patients with HER2-overexpressing esophageal adenocarcinoma.

     SECONDARY OBJECTIVES:

     I. To evaluate if the addition of trastuzumab to trimodality treatment increases the pathologic complete response rate and overall survival for patients with HER2-overexpressing esophageal adenocarcinoma.

     II. To develop a tissue bank of tumor tissue from patients with non-metastatic esophageal adenocarcinoma.

     III. To determine molecular correlates of complete pathologic response, disease-free survival, and overall survival for patients with HER2-overexpressing esophageal adenocarcinoma treated with neoadjuvant and maintenance trastuzumab.

     IV. To evaluate predictors of cardiotoxicity in patients with esophageal cancer treated with trastuzumab and chemoradiation.

     V. To evaluate adverse events associated with the addition of trastuzumab to trimodality treatment for patients with non-metastatic esophageal adenocarcinoma.

     TERTIARY OBJECTIVES:

     I. To determine if the addition of trastuzumab to trimodality treatment improves the patient-reported Functional Assessment of Cancer Therapy for Esophageal Cancer (FACT-E) Esophageal Cancer Subscale (ECS) score.

     II. To determine if an improvement in the FACT-E ECS score at 6-8 weeks post completion of neoadjuvant chemoradiation correlates with pathologic complete response.

     III. To determine if pathologic complete response correlates with the FACT-E ECS score at 1 year and/or 2 years from the start of chemoradiation.

     IV. To determine if the addition of trastuzumab to trimodality treatment improves the Swallow Index and Eating Index Subscale scores of the FACT-E.

     V. To determine if the addition of trastuzumab to paclitaxel, carboplatin, and radiation impacts quality-adjusted survival.

     OUTLINE: This is a multicenter study. Patients are stratified according to presence of adenopathy (yes vs no), and involved celiac nodes (absent vs presence ≤ 2 cm). Patients are randomized to 1 of 2 treatment arms.

     ARM I: Patients undergo radiotherapy once daily 5 days a week for 5.5 weeks. Patients also receive paclitaxel IV over 60 minutes and carboplatin IV over 60 minutes on days 1, 8, 15, 22, 29, and 36 and trastuzumab IV over 30-90 minutes on days 1, 8, 15, 22, 29, 36, and 57. Beginning 21-56 days after surgery, patients receive trastuzumab IV over 30-90 minutes. Treatment repeats every 21 days for 13 courses in the absence of disease progression or unacceptable toxicity.

     ARM II: Patients undergo radiotherapy once daily 5 days a week for 5.5 weeks. Patients also receive paclitaxel IV over 60 minutes and carboplatin IV over 60 minutes on days 1, 8, 15, 22, 29, and 36.

     Within 5-8 weeks after completion of radiotherapy, all patients undergo surgery.

     Patients may undergo blood and tumor tissue samples collection (during surgery) for correlative studies and tissue bank. Patients may complete the Functional Assessment of Cancer Therapy for Esophageal Cancer (FACT-E) and the EuroQol (EQ-5D) questionnaires at baseline and periodically during study.

     After completion of study therapy, patients are followed up every 4 months for 2 years and then yearly thereafter.

The purpose of this study is to determine whether cryotherapy is effective in the treatment of persistent high grade dysplasia (HGD) or early esophageal adenocarcinoma (IMCA) in patients who have not responded to radiofrequency ablation (RFA).

This study is being done to advance the understanding of how esophagus cancer and Barrett's Esophagus develop as well as ways to treat these conditions.  This will be done by analyzing blood and tissue to identify genes that may be involved in the development of esophagus cancer and Barrett's Esophagus.

A group of doctors and scientists at the Mayo Clinic in Rochester, Minnesota, along with doctors from many other medical centers throughout the US, are working together to advance our understanding of Barrett's esophagus and esophagus cancer. The main aim of the present study is to collect blood for future testing. Once all the samples have been collected, tests to identify genes that may be involved in the development of Barrett's will be performed. A future goal is to learn if there is a genetic difference between those people who have Barrett's and develop cancer, and those who do not.