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

Terminated

• Conditions: Barrett Esophagus; Deglutition Disorders; Neoplasm; Esophageal Neoplasms; GERD

• Registration Number: NCT00321958
• Lead Sponsor: University of Maryland, Baltimore

Brief Summary

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

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.

Study Timeline

• Study Start: 2006-04
• Study First Submitted: 2006-05-03
• Study First Submitted QC: 2006-05-03
• Study First Posted: 2006-05-04
• Primary Completion: 2007-05
• Study Completion: 2007-05
• Status Verified: 2022-01
• Last Update Submitted: 2022-01-25
• Last Update Posted: 2022-02-08

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 23

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
HGD or inoperable intramucosal or submucosal carcinoma and severe squamous dysplasia: measure of reduction in size of HGD or carcinoma	Study end	HGD or inoperable intramucosal or submucosal carcinoma and severe squamous dysplasia: measure of reduction in size of HGD or carcinoma

Secondary Outcome Measures

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

Trial Locations

Locations (1)

University of Maryland School of Medicine and Greenebaum Cancer Center; 🇺🇸 Baltimore, Maryland, United States