CryoBalloon Ablation for Treatment of Duodenal Adenomas (C2D2)

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

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.

Study Overview

• Status: Completed
• Conditions: Familial Adenomatous Polyposis; Duodenal Adenomas
• Intervention / Treatment: Device: CryoBalloon ablation

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Hospital
  • New York
    • Manhasset, New York, United States, 11030
      • Northwell Health
  • Pennsylvania
    • Danville, Pennsylvania, United States, 17822
      • Geisinger Medical Center
  • Texas
    • Dallas, Texas, United States, 75203
      • Methodist Dallas Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Sporadic duodenal adenomas between 1 to 5 cm in widest diameter
• FAP patient with Spigelman class 2, 3 or 4 (see definition below)
• Polyp characteristics: Non-polypoid lesions Paris 2A and 2B, or
• Sessile adenomas, occupying no more than 50% circumference of duodenum, and no more than 3 duodenal folds
• Individuals must be considered high risk for surgery or endoscopic resection, due to complication risk, or declined standard therapies.
• Prior endoscopic mucosal resection (EMR) or saline-assisted polypectomy allowed if polyp characteristics meet inclusion criteria.

Exclusion Criteria:

• Suspected or proven duodenal carcinoma
• Paris 1p pedunculated, Paris 2c, or 3 lesions
• Paris 1s lesion > 4 mm thick (estimated with closed biopsy forceps)
• Ampullary lesion or lesion involving the ampulla
• Prior failed ablative treatment with Argon Plasma Coagulation, laser, or cryotherapy
• Pre-existing esophageal, gastric, pyloric, or duodenal stenosis/stricture preventing advancement of a therapeutic endoscope during screening/baseline esophagogastroduodenoscopy (EGD.) Subjects are eligible if the stenosis/stricture is dilated to at least 15mm, but baseline treatment may need to be delayed.
• Any endoscopically-visualized abnormalities such as ulcers, masses or nodules during screening/baseline EGD within 3 cm of the treatment area.
• Subjects with nodular polyps or suspicion of invasive cancer by white light endoscopy /enhanced imaging/biopsy identified during screening/baseline EGD
• Suspicion of malignancy by abdominal or endoscopic ultrasound imaging based on malignant lymph nodes, invasion of lesion beyond mucosa.
• EMR or polypectomy < 6 weeks prior to baseline treatment.
• Untreated invasive esophageal malignancy, including margin-positive EMR.
• Active duodenitis in treatment zone during screening/baseline EGD.
• Severe medical comorbidities precluding endoscopy, or limiting life expectancy to less than 2 years in the judgment of the endoscopist.
• Uncontrolled coagulopathy or inability to be off anticoagulation or anti-platelet medication per standards of the institutions performing cryoablation.
• Known portal hypertension, visible esophageal, gastric, or duodenal varices, or history of varices.
• General poor health, multiple co-morbidities placing the patient at risk, or otherwise unsuitable for trial participation.
• Pregnant or planning to become pregnant during period of study participation.
• Patient refuses or is unable to provide written informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: cryoballoon ablation; Individuals with duodenal adenomas (DAs) and FAP with Spigelman class 2,3 or 4, treated with cryoballoon ablation (intervention), and individuals with at least 1 sporadic duodenal adenoma (DA) between 1-5 cm in maximum diameter, treated with cryoballoon ablation (intervention).	Device: CryoBalloon ablation; Endoscopic cryoablation (cryogen is nitrous oxide) using a CryoBalloon catheter to ablate up to 4 separate DAs.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of CryoBalloon Ablation in Treating Non-ampullary Non-polypoid Duodenal Adenomas (DAs) as Assessed by Participants With Adverse Events	To assess participants with any adverse event following cryoablation using the C2 cryoballoon system (per patient analysis). This includes serious adverse events (hospitalization, emergency room visit, bleeding requiring intervention) and post-procedure upper abdominal pain, nausea and gas-bloat	1 year
Participants With Complete Eradication of DA	Complete eradication (CE) rate of DAs as assessed by a combination of endoscopic and pathologic absence of adenomatous tissue in treated areas.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Technical Failure Rate	Technical failure rate is the number of patients with any treatment procedure of cryoballoon ablation that did not complete delivery of cryogen to all targeted sites.	1 year
Progression to High Grade Dysplasia or Duodenal Cancer	Progression: Patients with progression of dysplasia grade to high grade dysplasia or invasive cancer, compared to baseline biopsies, at any time during the study.	1 year
Number of Patients With Complete Eradication of All Eligible Treated DAs at 1 Year	Number of patients with duodenal adenomas with completely eradication of all eligible treated DAs at 1 year, combining FAP and sporadic DA patients	1 year
Mean Number of CryoBalloon Treatments Per Patient to Achieve Complete Eradication of DAs	Mean number of CryoBalloon treatments for each patient to achieve complete eradication of all eligible treated DAs by one year	1 year
Eligible Duodenal Adenomas Treated	duodenal adenomas measuring between 1cm-5cm treated with CryoBalloon ablation.	1 year

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: Pentax Medical
• Investigators: Principal Investigator: Marcia I. Canto, MD, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (Actual): May 13, 2019
• Primary Completion (Actual): June 1, 2025
• Study Completion (Actual): June 1, 2026

Study Registration Dates

• First Submitted: February 15, 2019
• First Submitted That Met QC Criteria: February 19, 2019
• First Posted (Actual): February 20, 2019

Study Record Updates

• Last Update Posted (Actual): August 5, 2026
• Last Update Submitted That Met QC Criteria: August 3, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Genetic Diseases, Inborn; Intestinal Diseases; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Neoplasms, Glandular and Epithelial; Colonic Diseases; Adenoma; Neoplastic Syndromes, Hereditary; Adenomatous Polyps; Intestinal Polyposis; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Adenomatous Polyposis Coli
• Other Study ID Numbers: IRB00163804

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Submit request to P.I. and study team with study goal.
• IPD Sharing Time Frame: 4 years
• IPD Sharing Access Criteria: Submit request to P.I. and study team with study goal.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes