CryoBalloon Focal Ablation System for Residual Barretts Esophagus Post Ablation; a Pilot Study.
Phase: NA
Conditions: Barrett's Esophagus
Sponsor: Mayo Clinic

 
 
The use of CryoBalloon Focal Ablation 
System for residual Barrett's Esophagus 
Post ablation; a pilot study. 
 
 
NCT02230410 
 
April 4, 2016 

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General Study Information 
 
Principal Investigator:       Kenneth Wang MD 
 
 
 
 
 
 
 
 
Study Title:    The use of CryoBalloon Focal Ablation System for residual Barrett's Esophagus Post ablation; a 
pilot study. 
 
Protocol version number and date:     Version 1 June 2014 
 
Purpose 
 
Hypothesis:  Radiofrequency ablation (RFA) is a commonly used method for eliminating Barrett’s esophagus 
(BE). RFA is highly effective, yet there is a set of patients who continue to have persistent dysplasia or 
intestinal metaplasia despite several treatments, thus this population requires follow up endoscopic therapy with 
a different ablative modality such as cryotherapy.  
 
Aims, purpose, or objectives: 
The primary objective of this study is to evaluate the usefulness of the C2 CryoBalloon Focal Ablation (510K 
cleared K131523, C2 Theraputics, Redwood City CA) in treating patients with persistent Barrett’s Esophagus 
(less than 2 cm) despite 2 or more serial Radio Frequency ablation or endoscopic mucosal resection treatment 
sessions.  
 
Background (Include relevant experience, gaps in current knowledge, preliminary data, etc.):   
 
Barrett’s esophagus (BE) is a pre-neoplastic condition formed by the metaplasia of the normal squamous 
mucosa of the distal esophagus into a specialized intestinal mucosa. Its development is mostly associated with 
chronic injury from gastroesophageal reflux. BE is widely considered the leading risk factor for the 
development of esophageal adenocarcinoma (EAC). (1) In 2009 alone, EAC accounted for 14,500 deaths in the 
U.S.(2)  It is one of the fastest growing malignancies which carries a dismal prognosis of less than 15% survival 
in a 5-year period.(3) 
 
The development of ablative therapy for BE with high grade dysplasia (HGDDYS) aims to prevent neoplastic 
progression to EAC.  Several emerging endoscopic strategies have become attractive to gastroenterologists as 
standard esophagectomy portends 4% to 12% perioperative mortality with other long term complications.(4) 
Endoscopic mucosal resection (EMR), in spite of its potential therapeutic and diagnostic advantages, requires 
further endoscopic skills and procedural time. Radiofrequency ablation (RFA) is another ablative technique. 
RFA employs bipolar electrodes, which deliver ablative energy to the tissue.(5) The latest results of the AIM 
Dysplasia Trial 10 at their 2-year follow-up shows 85% and 83% eradication of dysplasia and intestinal 
metaplasia, respectively, after intention-to-treat analysis.(6)At these rates, there is a set of patients who continue 
to have persistent dysplasia or intestinal metaplasia despite serial RFA treatments and may benefit from a 
different ablative modality such as cryotherapy. 
 
 

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Subject Information – charts, records, images, or specimens are considered ‘subjects’ 
 
Target accrual: In this pilot study we propose to enroll up to 20 participants. We estimate that due to potential of 
unforeseen ulcerations, lesions or other abnormalities at the time endoscopy we may need to invite 24 
participants to meet our accrual target.  
 
Subject population:   
Inclusion Criteria 
 
Eligible patients for enrollment in this study must fulfill all of the following criteria: 
 
a)  
Age > 18 years old 
 
b) 
Able to provide informed consent 
 
c) 
Patients with unifocal or multifocal BE with 2 cm who have failed at least 2 serial RFA or other 
endoscopic therapy such as Endoscopic Mucosal resection.  
 
 
 
4.2 
Exclusion Criteria 
 
 
Exclusion from the study with any of the following: 
 
 
a) 
Age younger than 18 years old 
 
b) 
Presence of esophageal varices 
 
c) 
Esophageal stricture precluding passage of an endoscope  
 
d) 
Inability to provide informed consent 
 
e) 
Esophageal cancer (T2 and above) 
 
f)  
 Coagulopathy with INR > 2.0, thrombocytopenia with platelet counts < 50,000 
 
g)  
pregnancy (if required a pregnancy test would be performed as part of routine clinical care) 
 
Will a Certificate of Confidentiality be obtained? No 
 
 
 
 

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Study Design  
 
Methods: Describe, in detail, the research activities that will be conducted under this protocol:   
 
In this pilot study results of treatment response will be documented. During clinically indicated endoscopic 
procedures, the Barrett’s segment length, length and presence of islands or tongues of Barrett’s mucosa, mucosa 
abnormalities (type and size) will be documented. The battery-powered Cryoballoon Focal Ablation System 
(CbFAS) is a 510K cleared disposable through-the-scope balloon-based catheter made of conformable material 
obviating the need for sizing. The balloon catheter will place at the area of persistent visible Barrett’s mucosa (2 
cm. or less) for treatment following standard endoscopic technique. Upon activation by the physician, the 
balloon probe at the end of the catheter is simultaneously inflated and cooled with nitrous oxide.  The balloon 
probe comes in contact with the wall of the target tissue and ablates unwanted tissue. Nitrous oxide is fully 
contained within the balloon.  The nitrous oxide gas exits the patient through the proximal end of the catheter. 
The participants will be here for clinically indicated endoscopy and therapy. Patients will return in 3 months for 
clinically indicated endoscopy and surveillance of Barrett’s Esophagus and/or esophageal cancer. At that 
endoscopy the Barrett’s segment length, length and presence of islands or tongues of Barrett’s mucosa, mucosa 
abnormalities (type and size) will again be documented to evaluate results. Results of clinical histological 
specimens obtained at both endoscopies that have been reviewed by expert GI Pathologists per clinical routine 
for classification of adenocarcinoma, high-grade dysplasia, low-grade dysplasia, indefinite for dysplasia, non-
dysplastic intestinal metaplasia, normal squamous mucosa and normal gastric mucosa as established guidelines 
will be documented. Patient demographics, Endoscopy and Pathology results will be review in the Electronic 
Medical record including the GI Endoscopy database, MICS and Synthesis. Patients will be identified for 
participation from the GI Endoscopy database. Participants may have up to three cryo ablation endoscopic 
procedures performed.  
 
1. 
Levine DS, Rubin CE, Reid BJ, Haggitt RC. Specialized metaplastic columnar epithelium in Barrett's 
esophagus. A comparative transmission electron microscopic study. Lab Invest 1989;60:418-32. 
2. 
Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin 
2009;59:225-49. 
3. 
Umar SB, Fleischer DE. Esophageal cancer: epidemiology, pathogenesis and prevention. Nature clinical 
practice Gastroenterology & hepatology 2008;5:517-26. 
4. 
Swisher SG, Deford L, Merriman KW, et al. Effect of operative volume on morbidity, mortality, and 
hospital use after esophagectomy for cancer. J Thorac Cardiovasc Surg 2000;119:1126-32. 
5. 
Fleischer DE, Overholt BF, Sharma VK, et al. Endoscopic ablation of Barrett's esophagus: a multicenter 
study with 2.5-year follow-up. Gastrointest Endosc 2008;68:867-76. 
6. 
Inadomi JM. Time to Burn? Endoscopic Ablation for Barrett's Esophagus. Gastroenterology 
2011;141:417-9. 

Minimal Risk Protocol Template [IRB 10429.004] 
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Check all that apply. If none apply, leave blank: 
 
  This is a multisite study involving Mayo Clinic and non-Mayo Clinic sites.  
When checked, describe the research procedures/activities being conducted only at Mayo Clinic: 
 
  Mayo Clinic staff will be engaged in research activity at a non-Mayo Clinic site.  When checked, provide 
the location and a detailed description of the Mayo Clinic research staff involvement. 
 
 
  This study is to establish and/or maintain an ongoing database or registry for research purposes only. 
 
  The research involves contact or interaction with subjects, for example, surveys, questionnaires, 
observation, blood draw. 
 
  The study involves audiotaping or videotaping   
 
 
 
 
Blood Collection 
 
If this study involves prospective blood collection by finger, heel, ear stick or venipuncture, complete the 
following:  
 
 
  From healthy, non pregnant, adult subjects who weigh at least 110 pounds. For a minimal risk 
application, the amount of blood drawn from these subjects may not exceed 550ml in an 8 week period 
and collection may not occur more frequently than 2 times per week. 
Volume per blood draw: _____ml   
Frequency of blood draw (e.g. single draw, time(s) per week, per year, etc.) _______ 
 
 
  From other adults and children considering age, weight, and health of subject. For a minimal 
risk application, the amount of blood drawn from these subjects may not exceed the lesser of 50 ml or 3 
ml per kg in an 8 week period, and collection may not occur more frequently than 2 times per week. 
Volume per blood draw: _____ml 
Frequency of blood draw (e.g. single draw, time(s) per week, per year, etc.)_______  
 
 
 
 

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Review of Chart, Images, Specimens 
Provide the date range for collection of data and/or specimens that will be included in your research dataset.  
(Example: 01/01/2000 to 12/31/2012)  
Date range: From ___/___/_____  to ___/___/_____ 
 
Check all that apply: 
 
  This study involves only data and/or specimens that exist at the time this application is submitted to the IRB 
(IRB submission date). No data or specimens will be collected beyond this date.  
 
 
  This study involves only data and/or specimens that will be collected after submission to the IRB. 
 
  The study involves data and/or specimens that exist at the time of submission to the IRB and data and/or 
specimens that will be collected after submission to the IRB, for example a study that includes collection of 
existing data and prospective collection of specimens. 
 
  Data and/or specimens used in this study are collected under another IRB protocol. When checked, provide 
the IRB number(s) from which the research material will be obtained and check the box below to attest that 
subjects have provided consent for future use of their data and/or specimens, as described in this protocol.  
 
 
IRB Number(s): 
 
 
□Subjects have provided consent for use of their data and/or specimens, as described in this protocol. 
 
  Other data sources will be utilized in this study. When checked, provide all data sources: 
 
 
Data Confidentiality, HIPAA Subject Identifiers 
 
Review the list of subject identifiers below and, if applicable, check the box next to each subject identifier being 
recorded at the time you are collecting/abstracting data/specimens for use in this study. 
 
Subject Identifiers:  Individually identifiable information, including demographic data, that identifies the 
individual or for which there is reasonable basis to believe it can be used to identify the individual.  NOTE: 
Identifiers apply to subjects enrolled in your study and to the subject’s relatives, household members, 
employers, etc. 
 
Internal refers to subject identifiers that will be included in the dataset maintained by the study team. 
External refers to subject identifiers that will be shared with persons outside of the immediate study team, for 
example, sent to an external collaborator or shared with a national registry.  
 

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SUBJECT IDENTIFIERS 
Check all that apply 
INTERNAL 
IDENTIFIER 
EXTERNAL 
IDENTIFIER 
Name 
 
 
Social Security number 
 
 
Medical record/patient registration number, lab accession, specimen or 
radiologic image number 
X 
 
Study number, subject ID, or any other unique identifying number, 
characteristic or code that can be used to link the identity of the subject to the 
data 
X 
 
Dates: All elements of dates [month, day, and year] directly related to an 
individual. Their birth date, date of death, date of diagnosis, etc.   
Note: Recording a year only is not a unique identifier.  
X 
 
Medical device identifiers and serial numbers 
 
 
Biometric identifiers, including finger and voice prints, full face photographic 
images and any comparable images 
 
 
Web Universal Resource Locators (URLs), Internet Protocol (IP) address 
numbers, email address 
 
 
Street address, city, county, precinct, zip code, and their equivalent geocodes 
 
 
Phone or fax numbers 
 
 
Account, member, certificate or professional license numbers, health 
beneficiary numbers 
 
 
Vehicle identifiers and serial numbers, including license plate numbers 
 
 
If None of the above identifiers will be recorded or maintained in the 
dataset and/or sent outside of the study team, please check “None”. 
 None 
X None 
 
 
Statistical Information 
 
Note: Power analyses and study endpoints are not needed for a pilot or feasibility studies.  
 
 
X No statistical information. If checked, please explain: Pilot study, small study numbers.  
 
 
Statistical Considerations 
 
Power Statement:   
    
 
Data Analysis Plan:  
 

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Endpoints 
    
 
Primary:  
 
       
 
 
 
 
Secondary: