Endoesophageal Cryotherapy For Ablating Barrett's Esophagus and Early Stage Esophageal Cancer - Full Text View

Sponsors and Collaborators:	Walter Reed Army Medical Center CSA Medical, Inc.
Information provided by:	Walter Reed Army Medical Center
ClinicalTrials.gov Identifier:	NCT00628784

Purpose

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).

Condition	Intervention	Phase
Barrett's Esophagus	Procedure: Endoscopic spray cryotherapy	Phase IV

MedlinePlus related topics: Cancer Endoscopy Esophageal Cancer Esophagus Disorders

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Active Control, Single Group Assignment, Safety/Efficacy Study
Official Title:	Endoesophageal Cryotherapy: A New Technique For Ablating Barrett's Esophagus And Early Stage Esophageal Cancer

Further study details as provided by Walter Reed Army Medical Center:

Primary Outcome Measures:

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. [ Time Frame: These outcomes are measured at each endoscopy, with limits set on the number of procedures that can be done based on group assignment. ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Assess the incidence of side effects, complications, adverse events and number of treatment sessions needed to reach primary endpoints. [ Time Frame: Measured throughout the protocol during the treatment phase with cryotherapy. ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	100
Study Start Date:	March 2007
Estimated Study Completion Date:	March 2012
Estimated Primary Completion Date:	March 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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 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.
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 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.
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 After passing a special orogastric venting tube, the cryocatheter is used to spray liquid nitrogen onto the tumor to achieve a white frost (frozen state) for 20 seconds. A 45-60 sec thaw is allowed and then retreatment x 2 for a total of 60 seconds therapy per session. Repeat treatments are permitted every 2 weeks for a maximum of 8 treatments.
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 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.

Show Detailed Description

Eligibility

Ages Eligible for Study:	18 Years to 85 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

** 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)

Exclusion Criteria:

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00628784

Contacts

Contact: John D Horwhat, MD

202-782-5263

john.horwhat@na.amedd.army.mil

Locations

United States, District of Columbia
Walter Reed Army Medical Center	Recruiting
Washington, District of Columbia, United States, 20307
Principal Investigator: John D Horwhat, MD

Sponsors and Collaborators

Walter Reed Army Medical Center

CSA Medical, Inc.

Investigators

Principal Investigator:

John D Horwhat, MD

Walter Reed Army Medical Center

More Information

Responsible Party:	Gastroenterology Service Walter Reed Army Medical Center ( LTC John David Horwhat MD FACG )
Study ID Numbers:	06-14034
Study First Received:	February 25, 2008
Last Updated:	July 22, 2008
ClinicalTrials.gov Identifier:	NCT00628784
Health Authority:	United States: Federal Government

Keywords provided by Walter Reed Army Medical Center:

Dysplasia
Ablation
Squamous dysplasia
Early esophageal adenocarcinoma
Cryotherapy

Study placed in the following topic categories:

Digestive System Neoplasms
Esophageal disorder
Gastrointestinal Diseases
Esophageal Neoplasms
Digestive System Abnormalities
Digestive System Diseases
Head and Neck Neoplasms

Gastrointestinal Neoplasms
Barrett Esophagus
Esophageal Diseases
Adenocarcinoma
Congenital Abnormalities
Esophageal neoplasm

Additional relevant MeSH terms:

Neoplasms
Neoplasms by Site

ClinicalTrials.gov processed this record on January 16, 2009