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Subjects undergoing CbFAS treatment as part of their clinical care for their condition.

CryoBalloon Focal Ablation System

Lindsay Cortright, MA

Susan Moist, MPH

Sharon Tang

Shajan Peter, MD

Keval Thakkar

Farhat Ahmed

Shervin Shafa, MD

Hilary Cosby

Marcia Canto, MD

Caryn Anderson

Melissa Passe

Prasad Iyer, MD

Molly Stewart

Victoria Barone

Arvind Trindade, MD

Michel Cohen

Michael Smith, MD

Katharine Boyce

Rowena Fang

Julian Abrams, MD

Julia Kim

Shilpa Karanjit

Nicholas J Shaheen, MD, MPH

Wendy Brock

Amitabh Chak, MD

John Dumot, MD

Nikolas Antinnes

Harshit Khara, MD

David Diehl, MD

Whitney Brako-Kusi

Ashley Warden

Puja Sukwhani Elias

Brenda Hoffman

Angie Rivera

Nirav Thosani, MD

Nicholas J Shaheeen, MD, MPH

A multicenter, prospective, single arm, non randomized clinical trial to evaluate the safety and efficacy of the C2 CryoBalloon Focal Ablation System (CbFAS) for the treatment of persistent dysplasia or intestinal metaplasia (IM) in the tubular esophagus after 3 or more radiofrequency ablations (RFA) for dysplastic BE, or \<50% eradication of Barrett's Esophagus (BE) after 2 RFA treatments.

Eligibility will be determined based on historical local pathology and medical record information. Informed consent will be obtained and eligible subjects will be treated with the Cryoballoon Focal Ablation System (CbFAS) at baseline.

Subjects will return every 3 months +/- 6 weeks for repeat treatment for up to 12 months OR until complete eradication of intestinal metaplasia (CEIM) and complete eradication of dysplasia (CED) are achieved (at which point subjects enter the follow-up phase), whichever occurs first.

Treatment procedures will be performed on an outpatient basis according to the site's standards of care for anesthesia and sedation during esophagogastroduodenoscopy (EGD) procedures. EGD examinations will be performed using high definition White Light Endoscopy (WLE), plus Narrow Band Imaging (NBI) or i-SCAN to assess BE Prague Score and identify tissue landmarks and ablation zones.

A high definition endoscope will be used for all ablations performed with the CryoBalloon Focal Ablation System (CbFAS). The System will be used according to the instructions for use provided with the product and in accordance with the current standard of care for treatment of BE.

Repeat cryoablation may be performed if esophageal columnar mucosa is visible on EGD or if intervening biopsies (if a site chooses to obtain intervening biopsies as standard of care) are positive for any esophageal columnar epithelium until complete eradication of all unwanted tissue is achieved.

Intervening endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) after enrollment may be performed for nodular areas detected after baseline. EMR/ESD may be performed at the same session as the cryoablation if the EMR/ESD site is \>=3cm away from the ablation target site. Cryoablation should be performed before EMR/ESD. If the EMR/ESD site is within 3cm of target treatment area, then CbFAS will be delayed for at least 6 weeks.

Residual islands of columnar mucosa of \<5 mm in diameter each and \<= 3 total can be treated with Argon Plasma Coagulation (APC) and/or CbFAS at the discretion of the treating physician to avoid over treatment of neo-squamous mucosa.

Stenosis requiring treatment based on the physician's discretion, which develops after enrollment, will be treated with standard of care balloon- or wire-guided dilation. Cryoablation may be performed at the same session if the dilated site is \>= 3 cm from the target cryoablation site. Otherwise, cryoablation will be postponed to another visit within 1 month +/- 2 weeks.

When CbFAS treatment is received, subjects will be asked to complete assessments immediately after CbFAS treatment, and will be contacted 1 day, 7 days, and 30 days after the procedure.

If no visible BE is present during the endoscopy, then biopsies will be taken following the standard Seattle biopsy protocol (4 quadrant biopsies at 1cm intervals starting at the gastric cardia 1cm distal to the gastroesophageal junction (GEJ) (top of the gastric folds) and continuing proximally throughout the length of the original extent of BE, including any neosquamous or re-epithelialized tissue).

Biopsies will be read by local expert pathologist. If biopsies indicate CEIM and CED, then subjects will enter the 12 month follow-up phase. If biopsies do not indicate CEIM and CED, then subjects will return for additional CbFAS treatment in 3 months +/-6 weeks.

Non-responders are defined as subjects who have not achieved CEIM and CED at 12 months post baseline CbFAS treatment. Non-responders at 12 months will exit the study and continue treatment at the physician's discretion and according to standard of care at each site.

Subjects who achieve CEIM and CED within 12 months of the baseline CbFAS procedure will enter a 12 month follow-up phase. Subjects will be followed per routine care guidelines for their condition, described below:

Subjects with baseline LGD will return at 6 and 12 months from the initial CEIM and CED date for follow-up (+/-2 weeks). Subjects with baseline HGD or IMC will return at 3, 6, 9, and 12 months from initial CEIM and CED date for follow-up (+/- 2 weeks).

During follow-up procedures, high definition WLE, plus NBI or i-SCAN will be used to assess Prague score, and biopsies will be taken following the standard Seattle biopsy protocol (4 quadrant biopsies at 1cm intervals starting at the gastric cardia 1cm distal to the gastroesophageal junction (GEJ) (top of the gastric folds) and continuing proximally throughout the length of the original extent of BE, including any neosquamous or re-epithelialized tissue). Biopsies will be read by local expert pathologist.

If recurrent BE is detected during follow-up endoscopy with biopsy demonstrating compatible histology, then subjects will be exited from the study and treated at the physician's discretion.

Study participation is complete if: 1) Subject has not reached CEIM and CED at 12 month post baseline treatment; or 2) If BE or dysplasia recur after initial CEIM and CED post enrollment; or 3) After completion of the 12 month follow-up EGD with biopsies.

Nitrous Oxide For Endoscopic Ablation of Refractory Barrett's Esophagus (NO FEAR-BE)

Stratified by prior type of ablation treatment and baseline grade (LGD or HGD) will also be reported.

Relation of serious adverse events to CryoBalloon device will be assessed by the PI

The device worked as expected on every application, defined as proportion of all CbFAS that perform as intended.

All columnar tissue that was planned to be treated was treated.

Percentage of subjects with progression of dysplasia from LGD to HGD or esophageal cancer, or progression of HGD to cancer at 12 months from enrollment date.

Time to complete eradication of intestinal metaplasia (CEIM). Survival curve analysis from first treatment.

Time to progression of dysplasia from LGD to HGD or esophageal cancer, or progression of HGD to cancer at 12 months from enrollment date. Survival curve analysis from first treatment.

Time to recurrence. Survival curve analysis from first treatment.

Risk factors associated with failure to respond to CryoBalloon ablation

Median number of CryoBalloon ablation treatments required to achieve CED and CEIM by 12 months from enrollment date.

Mean number of CryoBalloon ablation treatments required to achieve CED and CEIM by 12 months from enrollment date.

Proportion of subjects requiring narcotic analgesic at day 1 post treatment.

Proportion of subjects requiring narcotic analgesic at day 7 post treatment.

Proportion of subjects requiring narcotic analgesic at day 30 post treatment.

Median pain score immediately post-procedure day 1 as assessed by self-reported pain scale (0-10) where 0 is no pain and 10 is worst pain imaginable. Higher scores indicate more severe pain.

Median pain score 7 days after treatment as assessed by self-reported pain scale (0-10) where 0 is no pain and 10 is worst pain imaginable. Higher scores indicate more severe pain.

Median pain score 30 days after treatment as assessed by self-reported pain scale (0-10) where 0 is no pain and 10 is worst pain imaginable. Higher scores indicate more severe pain.

Mean pain score immediately post-procedure day 1 as assessed by self-reported pain scale (0-10) where 0 is no pain and 10 is worst pain imaginable. Higher scores indicate more severe pain.

Mean pain score 7 days after treatment as assessed by self-reported pain scale (0-10) where 0 is no pain and 10 is worst pain imaginable. Higher scores indicate more severe pain.

Mean pain score 30 days after treatment as assessed by self-reported pain scale (0-10) where 0 is no pain and 10 is worst pain imaginable. Higher scores indicate more severe pain.

For those who do not achieve CEIM and CED at 12 months from enrollment date, proportion of Barrett's Esophagus surface area reverted to neosquamous epithelium based on physician report.

Spots Global Cancer Trial Database for cryoballoon focal ablation system