Endoesophageal Cryotherapy For Ablating Barrett's Esophagus and Early Stage Esophageal Cancer

NCT00628784 | Unknown Phase 4 DMC

• 1 other identifier: 06-14034
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

In this prospective single center study, up to 25 patients with Barrett's esophagus with LGD or no dysplasia (Group 1), 25 patients with HGD/IMCA (Group 2), 25 patients with esophageal carcinoma confined to the esophageal wall (Group 3) and 25 patients with severe esophageal squamous dysplasia (Group 4) will be treated with endoscopic cryotherapy. This study is single arm and no blinding will be utilized. Interim analysis of the data will be reviewed with a DCI statistician after 14 patients in each group have been treated with cryotherapy and if safety and efficacy is documented to that point in time, we will request the ability to extend the enrollment to a maximum allowable amount of 25 patients per group. The proposed study duration is seven years, allowing two years for patient enrollment and 5 years for post treatment follow-up. Study duration per patient will total approximately six years. Patients with Barrett's esophagus with no dysplasia or low grade dysplasia (group 1) will be treated with cryotherapy at six week intervals until Barrett's mucosa is ablated or six treatments are administered. Patients with Barrett's HGD and IMCA or severe esophageal squamous dysplasia (groups 2 and 4) will be treated with cryotherapy at six-week intervals until Barrett's mucosa is ablated or six treatments are administered. More advanced mass lesions are typically more difficult to eradicate with ablative therapies and may progress faster than patients with IMCA, therefore, patients with more advanced cancer (group 3) will be treated every 2 weeks until the lesion is eradicated up to eight treatments. After cryotherapy treatment is complete (i.e. the esophagus has re-epithelialized with normal squamous epithelium for Groups 1, 2, 4 and the tumor is locally controlled/absent in Group 3), patients will be assessed by endoscopy and biopsy every three months for one year, every six months for two years, then annually for two years (flow sheet - appendix 1; study schedule - appendix 2).

Conditions

Barrett's Esophagus

Keywords

Dysplasia; Ablation; Squamous dysplasia; Early esophageal adenocarcinoma; Cryotherapy

Outcome Measures

Primary Outcomes (1)

• Confirm the feasibility and safety of endoscopic cryotherapy in patients with Barrett's esophagus with LGD, HGD, intramucosal cancer and in patients with severe squamous dysplasia.

  These outcomes are measured at each endoscopy, with limits set on the number of procedures that can be done based on group assignment.

Secondary Outcomes (1)

• Assess the incidence of side effects, complications, adverse events and number of treatment sessions needed to reach primary endpoints.

  Measured throughout the protocol during the treatment phase with cryotherapy.

Study Arms (4)

Group 1

EXPERIMENTAL

Specialized intestinal metaplasia (Barrett's esophagus) documented via endoscopic esophageal biopsy, with standard surveillance biopsies (four-quadrant biopsies obtained every 2-cm the entire length of the specialized intestinal metaplasia in the esophagus) performed within the past two years prior to study enrollment. Biopsies show either low grade dysplasia, indeterminate for dysplasia, or no dysplasia.

Procedure: Endoscopic spray cryotherapy

Group 2

EXPERIMENTAL

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. CT scan demonstrating no evidence of advanced esophageal cancer (extension into or through the wall or lymph node involvement). Endoscopic ultrasound\* (EUS) demonstrating no evidence of metastatic lymph node involvement or extension of carcinoma beyond the mucosa (T1).

Procedure: Endoscopic spray cryotherapy

Group 3

EXPERIMENTAL

Diagnosis of esophageal carcinoma (T1smN0 or T2N0 via EUS). Deemed inoperable based on the following criteria: co-morbid conditions such as severe heart, lung, kidney, or liver disease; or refusal of surgical intervention. CT scan demonstrating no evidence of advanced esophageal cancer (extension into or through the wall or lymph node involvement).

Procedure: Endoscopic spray cryotherapy

Group 4

EXPERIMENTAL

Diagnosis of severe dysplasia within esophageal squamous mucosa on pathology review. Deemed inoperable based on the following criteria: co-morbid conditions such as severe heart, lung, kidney or liver disease; or refusal of surgical intervention. CT scan demonstrating no evidence of advanced esophageal cancer (extension into or through the wall or lymph node involvement). EUS with no evidence of metastatic lymph node involvement or extension of carcinoma beyond the mucosa.

Procedure: Endoscopic spray cryotherapy

Interventions

Endoscopic spray cryotherapy PROCEDURE

A special orogastric venting tube is passed alongside the endoscope and the cryocatheter then used to perform cryotherapy. Liquid nitrogen is sprayed through the catheter to achieve a uniform white frost in a hemicircumferential sector for 10 seconds. A thaw time of 45-60seconds is observed. This freeze-thaw cycle is repeated x 3 for a total of 40sec cryotherapy per segment. This therapy is repeated every 6 weeks until visible re-epithelialization is seen or a maximum of 6 sessions. Once a squamous lining is seen, biopsies are taken throughout the original area to assess for buried Barretts. If none is seen, followup with 4 quadrant q2cm biopsies are taken at 3,6,9,12, 18, 24, 36, 48 months.

Also known as: Cryotherapy

Group 1; Group 2; Group 4

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \*\* You must be eligible for care within the Department of Defense (DEERS eligible) to be enrolled into this protocol \*\*
• Per Groups 1,2,3,4 (above)
• Specifically:
• Diagnosis of specialized intestinal metaplasia (Barrett's esophagus) with either low grade, indeterminate or no dysplasia (Group 1)
• high grade or intramucosal cancer and deemed inoperable based on co-morbid conditions such as severe heart, lung, kidney or liver disease; or refusal of surgical intervention; CT scan and EUS demonstrating no evidence of trans-mural tumor or lymph node involvement; pathology review of esophageal biopsies by 2 independent reviewers to include 1 from the Walter Reed Army Medical Center Pathology Department; presentation at tumor board (Group 2)
• T1smN0 or T2NO adenocarcinoma arising in Barrett's esophagus and all criteria as for group 2 (Group 3)
• diagnosis of severe squamous dysplasia and all criteria as for group 2 (Group 4)

You may not qualify if:

• Not eligible for care within the Department of Defense medical system
• Age less than 18 years or greater then 85 years (at time of entry)
• Co-morbid illness expected to cause death within 6 months
• Pregnancy (as determined by urine HCG)
• Medically unfit or other contraindications to tolerate upper endoscopy
• Inability to tolerate therapy with a proton pump inhibitor
• Refusal or inability to give consent

Sponsors & Collaborators

• Walter Reed Army Medical Center: lead
• CSA Medical, Inc.: collaborator

Study Sites (1)

Walter Reed Army Medical Center

Washington D.C., District of Columbia, 20307, United States

RECRUITING

MeSH Terms

Conditions

Barrett Esophagus; Adenocarcinoma Of Esophagus

Interventions

Cryotherapy

Condition Hierarchy (Ancestors)

Precancerous Conditions; Neoplasms; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• John D Horwhat, MD

  Walter Reed Army Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

John D Horwhat, MD

CONTACT

202-782-5263; john.horwhat@na.amedd.army.mil

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: FED

Study Record Dates

• First Submitted: February 25, 2008
• First Posted: March 5, 2008
• Study Start: March 1, 2007
• Primary Completion: March 1, 2010
• Study Completion: March 1, 2012
• Last Updated: July 24, 2008

Record last verified: 2008-07

Locations

US (1)