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Individuals with duodenal adenomas (DAs) and FAP with Spigelman class 2,3 or 4, treated with cryoballoon ablation (intervention)

Individuals with at least 1 sporadic duodenal adenoma (DA) between 1-5 cm in maximum diameter, treated with cryoballoon ablation (intervention)

Endoscopic cryoablation (cryogen is contained nitrous) using a CryoBalloon catheter to ablate up to 4 separate DA.

CryoBalloon ablation

Marcia I. Canto, MD

This multicenter prospective non-randomized interventional study (clinical trial) that will assess the safety and efficacy of cryoballoon ablation treatment using the C2 Cryoballoon device (Pentax Medical Corporation) as an alternative primary treatment modality for sporadic and familial nonampullary nonpolypoid (flat) duodenal adenomas.

Duodenal adenomas are precursors to adenocarcinoma. Treatment with endoscopic polypectomy is technically challenging problematic and associated with a high rate of complication - overall 26%, with bleeding 22-40%, higher with larger polyps. Surgery to remove these benign polyps would be a Whipple operation, which has a high morbidity and 1-4% mortality rate. Medical therapies like celecoxib decrease the number of polyps but do not prevent cancer.

This multicenter prospective cohort study will assess the safety and efficacy of cryoablation treatment as an alternative primary treatment modality for sporadic and familial nonampullary nonpolypoid (flat) duodenal adenomas

Prospective studies have demonstrated the safety and efficacy of nitrous oxide focal cryoballoon ablation for complete eradication of Barrett's esophagus (including a clinical trial published by the Principal Investigator), which is intestinal metaplasia, which is histologically similar to normal duodenal mucosa.

When inflated, the cryoballoon flattens the duodenal folds allowing improved visibility of the duodenal lesions. The focal ablation allows precise targeting and avoidance of the ampulla to minimize pancreatitis risk.

Two cases at Johns Hopkins Hospital have been treated successfully and safely using cryogen dose of 10 seconds. The procedures were easy and short, with excellent views of the lesion with balloon inflation and high definition endoscope. No major adverse events, pain requiring treatment, or bleeding were noted. Minor adverse events included transient abdominal bloating lasting for \< 3 days in 1 patient. In one patient with sporadic laterally spreading large Paris 2A polyp who declined standard treatments, complete eradication was achieved with 2 ablation sessions.

In the other patient with familial adenomatous polyposis (FAP) who had 2 hospitalizations for post-polypectomy bleeding after duodenal EMR, complete eradication was noted after 1 treatment of 3 Paris 2A and 2B adjacent polyps.

Follow-up of these two patients shows no recurrence \> 1 year and at the most recent follow-up procedures. Clinical and endoscopic surveillance continues.

In addition, another physician at the University of Texas Health Science Center at San Antonio (UTHSCSA) reported another two patients with duodenal adenomas in her practice treated successfully with cryoballoon ablation without complications. Two other collaborating physicians at Memorial Hermann Texas Medical Center in Houston, Texas, and Geisinger Medical Center in Pennsylvania have also reported favorable response of these challenging neoplasms to endoscopic cryoballoon ablation. The group is currently preparing a case series report and a separate Institutional Review Board application is being submitted.

This study may impact on the management of patients with duodenal adenomas by demonstrating the potential for safe and effective non-operative eradication using cryoballoon ablation. The safety profile of endoscopic cryoballoon ablation is likely to be better than endoscopic resection based on a large clinical and research experience in Barrett's esophagus patients (\>250) and small clinical experience in duodenal adenoma patients, with \<=5% bleeding, no perforation, and transient, mild post-treatment discomfort.

Non-randomized pilot study of highly selected patients

CryoBalloon Ablation for Treatment of Duodenal Adenomas

Safety and Efficacy of Cryoballoon Ablation for Treatment of Sporadic and Familial Nonampullary Nonpolypoid Duodenal Adenomas (the C2D2 Trial)

Submit request to P.I. and study team with study goal.

To assess incidence of treatment-related adverse events following cryoablation using the C2 cryoballoon system, defined by frequency or number of adverse events in all treated patients (per patient analysis).

To assess incidence of treatment-related adverse events following cryoablation using the C2 cryoballoon system, defined by frequency or number of adverse events in all treatment procedures (per procedure analysis).

Complete eradication (CE) rate of DAs as assessed by a combination of endoscopic and pathologic absence of adenomatous tissue in treated areas.

Endoscopic assessment: percent change in adenoma size by blinded review by 3-person expert panel of still images with region of interest marked by tattoo - per lesion analysis and per patient analysis.

Technical failure rate is the proportion of treatment procedures with cryoballoon ablation that did not complete delivery of cryogen to all targeted sites.

Percent change in Spigelman classification for polyp burden in FAP patients from baseline to 1 year after treatment is completed. The Spigelman classification assigns points based upon polyp number, polyp size, histology and dysplasia grade, where Stage 0 = 0 points, Stage I = 1-4 points, Stage II = 5-6 points, Stage III = 7-8 points, and Stage IV = 9-12 points. The higher the score, the more severe or advanced the FAP disease in the duodenum.

Progression rate: percentage of patients with progression of dysplasia grade to high grade dysplasia or invasive cancer, compared to baseline biopsies, at any time during the study.

Time to complete eradication (in months) of all duodenal adenomas in each patient

Time to complete eradication (in months) of each treated DA lesion

Median number of cryoballoon ablation treatments to achieve complete eradication.

Pentax Medical

Johns Hopkins University

Barrett Esophagus

Precancerous Conditions

Esophageal Diseases

Analgesics

Central Nervous System Depressants

All Drugs and Chemicals

Nitrous Oxide

C2 CryoBalloon 180 Ablation System will be used to ablate visible Barrett's esophagus

The C2 CryoBalloon 180° Ablation System is a cryosurgical device with a nitrous oxide cooled balloon probe that is compatible with upper gastrointestinal therapeutic endoscopes.

C2 CryoBalloon 180° Ablation System

Koen Munters, Msc

Erik Schoon, Prof. dr.

Jacques Bergman, Prof. dr.

Bas Weusten, Prof. dr.

Arjun Koch, Dr.

Wouter Nagengast, Prof. dr.

Evaluate the efficacy and safety of the C2 CryoBalloon 180° Ablatie Systeem (CBAS180) at decremental doses for the treatment of dysplastic Barrett's epithelium.

Cryoballoon ablation is a relatively new ablation technique for the treatment of dysplastic Barrett's esophagus (BE). Previous studies with this technique have shown that treatment is safe and effective. When compared to other ablation techniques, cryoballon ablation has several potential advantages, including less pain and less complications such as stricture formation after treatment. Recently, a cryoballoon ablation system has become available which enables treatment of larger esophageal surfaces. Although a recent clinical study with this new device has shown promising results, the lowest possible dose that optimally balances safety and efficacy is still unknown.

This study is a multicenter, prospective, intervention study consisting of two phases: the treatment phase and the follow-up phase.

During the treatment phase, patients will undergo an upper endoscopy during which CBAS180 treatment will be performed. Treatment consists of two CBAS180 applications, starting just below the gastroesophageal junction (GEJ), resulting in a circumferential ablation of 3cm in length. During the treatment phase, two doses will be tested consecutively starting with the lowest dose (i.e. 1.2mm/sec). For each dose a total of 25 patients will be included. An interim analysis will be performed after treatment of the first 25 patients with the lowest dose of 1.2mm/sec, before proceeding to treatment of the additional 25 patients with a higher dose of 1.1mm/sec.

The follow-up phase starts after CBAS180 treatment and ends after first follow-up endoscopy at 10 weeks (±2 weeks) after treatment. Therefore, the study duration will be approximately 3 months for each individual patient. The investigators expect to report the primary outcome for all participating patients within 2 years.

CBAS180 De-escalation Study

Clinical Trial to Evaluate Safety and Efficacy of the C2 Cryoballoon 180° Ablation System for the Treatment of Dysplastic Barrett's Esophagus: CBAS180 De-escalation Study

Efficacy (dose response) will be evaluated by the BE surface regression percentage after 1 circumferential treatment session, as evaluated by the EGD-Adjudication Committee (EGD-AC) and confirmed by histological evidence of eradication of BE.

Safety will be evaluated by the incidence of dose-related SAEs. Dose-related SAEs include pain in the treatment area greater than 6 (scored on a 0 to 10-point numeric rating scale (NRS)) at 24 hours post-treatment; symptomatic stricture requiring an additional EGD plus endoscopic dilation before first follow-up EGD; symptomatic stricture requiring endoscopic dilation at follow-up EGD; or any stricture (symptomatic or asymptomatic) preventing passage of the diagnostic endoscope at follow-up EGD.

Safety will be evaluated by the incidence of dose-related SAEs. Dose-related SAEs include pain in the treatment area greater than 6 (scored on a 0 to 10-point numeric rating scale (NRS)) at 7 days post-treatment; symptomatic stricture requiring an additional EGD plus endoscopic dilation before first follow-up EGD; symptomatic stricture requiring endoscopic dilation at follow-up EGD; or any stricture (symptomatic or asymptomatic) preventing passage of the diagnostic endoscope at follow-up EGD.

Safety will be evaluated by the incidence of dose-related SAEs. Dose-related SAEs include pain in the treatment area greater than 6 (scored on a 0 to 10-point numeric rating scale (NRS)) at 30 days post-treatment; symptomatic stricture requiring an additional EGD plus endoscopic dilation before first follow-up EGD; symptomatic stricture requiring endoscopic dilation at follow-up EGD; or any stricture (symptomatic or asymptomatic) preventing passage of the diagnostic endoscope at follow-up EGD.

Feasibility (technical success) defined as the percentage of patients in whom all BE could be treated as intended by the treating endoscopist.

Post-procedure pain in the area of the cryoablation treatment (scored on a 0 to 10-point numeric rating scale (NRS)), described as the median pain score directly after treatment.

Post-procedure pain in the area of the cryoablation treatment (scored on a 0 to 10-point numeric rating scale (NRS)), described as the median pain score 1 day after treatment.

Post-procedure pain in the area of the cryoablation treatment (scored on a 0 to 10-point numeric rating scale (NRS)), described as the median pain score 7 days after treatment.

Post-procedure pain in the area of the cryoablation treatment (scored on a 0 to 10-point numeric rating scale (NRS)), described as the median pain score 30 days after treatment.

Post-procedure dysphagia (scored on a 0-4 dysphagia score), described as the median dysphagia score directly after treatment.

Post-procedure dysphagia (scored on a 0-4 dysphagia score), described as the median dysphagia score 1 day after treatment.

Post-procedure dysphagia (scored on a 0-4 dysphagia score), described as the median dysphagia score 7 days after treatment.

Post-procedure dysphagia (scored on a 0-4 dysphagia score), described as the median dysphagia score 30 days after treatment.

Incidence of all serious and non-serious AEs up to 30 days post-treatment.

BE surface regression percentage after 1 circumferential treatment session as assessed by the treating endoscopist.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
CryoBalloon Ablation for Treatment of Duodenal Adenomas	NCT03847636	Duodenal Adenom... Familial Adenom...	CryoBalloon abl...	18 Years -	Johns Hopkins University
CBAS180 De-escalation Study	NCT05740189	Barrett's Esoph... Ablation Therap... Cryotherapy Cryoballoon Abl...	C2 CryoBalloon ...	18 Years -	St. Antonius Hospital
CryoBalloon Ablation for Treatment of Duodenal Adenomas	NCT03847636	Duodenal Adenom... Familial Adenom...	CryoBalloon abl...	18 Years -	Johns Hopkins University
CBAS180 De-escalation Study	NCT05740189	Barrett's Esoph... Ablation Therap... Cryotherapy Cryoballoon Abl...	C2 CryoBalloon ...	18 Years -	St. Antonius Hospital

Spots Global Cancer Trial Database for cryoballoon ablation