Study of Cryotherapy Treatment of Barrett's Esophagus and Early Esophageal Cancer

Study Overview
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Brief Summary
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The purpose of this study is to confirm the effectiveness and safety of a new medical device which sprays liquid nitrogen through an upper endoscope (cryotherapy) to treat Barrett's esophagus with high-grade dysplasia and early esophageal cancer. It is hypothesized that this treatment will remove the abnormal lining of the esophagus and allow the normal esophageal lining to return.

Detailed Description
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Barrett's esophagus (BE) with high grade dysplasia (HGD) is a precursor of esophageal adenocarcinoma. Eliminating this condition may control the current rapid rise of adenocarcinoma. Ablative techniques are attempted to avoid the high morbidity and mortality of esophagectomy or for use in patients who cannot undergo surgery. Current ablative techniques have achieved mucosal ablation with variable success but are associated with high cost, patient discomfort and/or significant complications. A novel device which sprays liquid nitrogen through an upper endoscope (cryotherapy) has been shown to be a safe and effective procedure to ablate the esophageal mucosa in swine and dog models and in pilot studies in humans. Successful reversal of BE, LGD, HGD and superficial adenocarcinoma and squamous cell carcinoma have been demonstrated when cryotherapy with this device is followed by healing of the esophageal lining in a low acid environment. This study is undertaken to demonstrate the efficacy and safety in the ablation of Barrett's esophagus with high-grade, neoplasia, and severe esophageal squamous dysplasia and to confirm preliminary results in humans.

Official Title
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Cryotherapy Ablation of Barrett's Esophagus and Early Esophageal Cancer

Conditions
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Barrett Esophagus, Esophageal Neoplasms, Deglutition Disorders, GERD, Neoplasm

Intervention / Treatment
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* Device: CSA System (CryoSpray AblationTM System)
* Device: CryoSpray Ablation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: High Grade-IMCancer: Diagnosis of Barrett's esophagus and high-grade dysplasia or intramucosal carcinoma Deemed inoperable based on the following criteria: co-morbid conditions such as severe heart, lung, kidney or liver disease; or refusal of surgical intervention after a thorough discussion of the highly experimental nature of cryotherapy CT scan of the chest and abdomen with oral and intravenous contrast (unless allergic), demonstrating no evidence of advanced esophageal cancer (extension into or through the wall or lymph node involvement) Endoscopic ultrasound evaluation demonstrating no evidence of metastatic lymph node involvement or extension of carcinoma beyond the mucosa Pathology review of esophageal biopsies by two independent reviewers, including at least one from the Department of Pathology at the University of Maryland, to confirm the diagnosis of Barrett's esophagus with HGD and/or IMCA Presentation and discussion at Thoracic Tumor Board Mucosal/submucosal cancer: Diagnosis of esophageal carcinoma Deemed inoperable based on the following criteria: co-morbid conditions such as severe heart, lung, kidney or liver disease; or refusal of surgical intervention after a thorough discussion of the highly experimental nature of cryotherapy CT scan of the chest and abdomen with oral and intravenous contrast (unless allergic), demonstrating no evidence of advanced esophageal cancer (extension through the wall or lymph node involvement) Endoscopic ultrasound evaluation demonstrating no evidence of metastatic lymph node involvement and primary lesion extending into submucosa or muscularis propria (T1smN0 or T2N0) Presentation and discussion at Thoracic Tumor Board Patients who have undergone previous ablation therapies are eligible for this study. Severe squamous dysplasia: Diagnosis of severe dysplasia within esophageal squamous mucosa Deemed inoperable based on the following criteria: co-morbid conditions such as severe heart, lung, kidney or liver disease; or refusal of surgical intervention after a thorough discussion of the highly experimental nature of cryotherapy CT scan of the chest and abdomen with oral and intravenous contrast (unless allergic), demonstrating no evidence of advanced esophageal cancer (extension into or through the wall or lymph node involvement) Endoscopic ultrasound evaluation demonstrating no evidence of metastatic lymph node involvement or extension of carcinoma beyond the mucosa Pathology review of esophageal biopsies by two independent reviewers, including at least one from the Department of Pathology at the University of Maryland, to confirm the diagnosis Presentation and discussion at Thoracic Tumor Board Exclusion Criteria: Age less than 18 years Co-morbid illness expected to cause death within 6 months Pregnancy Medically unfit or other contraindication to tolerate upper endoscopy Inability to tolerate therapy with a proton pump inhibitor (PPI) Refusal or inability to give consent

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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Arms and Interventions

| Intervention/Treatment |
| --- |
|Device: CSA System (CryoSpray AblationTM System)|10 second spray times|
|Device: CryoSpray Ablation|10 second spray times|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HGD or inoperable intramucosal or submucosal carcinoma and severe squamous dysplasia: measure of reduction in size of HGD or carcinoma | HGD or inoperable intramucosal or submucosal carcinoma and severe squamous dysplasia: measure of reduction in size of HGD or carcinoma | Study end | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HGD or inoperable intramucosal carcinoma: Rate of complete ablation of all BE and associated HGD or intramucosal carcinoma | HGD or inoperable intramucosal carcinoma: Rate of complete ablation of all BE and associated HGD or intramucosal carcinoma | Study midpoint and end | 
| Number of treatment sessions needed to ablate BE and associated HGD or intramucosal carcinoma | Number of treatment sessions needed to ablate BE and associated HGD or intramucosal carcinoma | Study end | 
| Rate of adverse events | Rate of adverse events | Throughout study | 
| Inoperable mucosal or submucosal carcinoma (T1mN0, T1smN0 and T2N0): Time to cancer recurrence | Inoperable mucosal or submucosal carcinoma (T1mN0, T1smN0 and T2N0): Time to cancer recurrence | Throughout study | 
| Inoperable severe squamous dysplasia: Rate of complete ablation of all dysplasia | Inoperable severe squamous dysplasia: Rate of complete ablation of all dysplasia | Study end | 
| Number of treatment sessions needed to ablate dysplasia | Number of treatment sessions needed to ablate dysplasia | Throughout study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Barrett Esophagus, Esophageal Neoplasm, Deglutition disorders, Cryotherapy, Cryosurgery, GERD, Neoplasm, Esophagus, Endoscopy, Digestive System