Safety and Efficacy of Cryoballoon Ablation for Treatment of Sporadic and Familial Nonampullary Nonpolypoid Duodenal Adenomas (the C2D2 Trial)
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- Enrollment
- 33
- Locations
- 7
- Primary Endpoint
- Safety of cryoBalloon ablation in treating non-ampullary non-polypoid duodenal adenomas (DAs) as assessed by the incidence of adverse events in all treated patients
Study Overview
Brief Summary
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.
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.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
Arms & Interventions
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).
Intervention: CryoBalloon ablation (Device)
Outcomes
Primary Outcomes
Safety of cryoBalloon ablation in treating non-ampullary non-polypoid duodenal adenomas (DAs) as assessed by the incidence of adverse events in all treated patients
Time Frame: 5 years
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).
Safety of cryoBalloon ablation in treating non-ampullary non-polypoid duodenal adenomas (DAs) as assessed by the incidence of adverse events in all treatment procedures
Time Frame: 5 years
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 rate of DAs
Time Frame: 1 year
Complete eradication (CE) rate of DAs as assessed by a combination of endoscopic and pathologic absence of adenomatous tissue in treated areas.
Safety of CryoBalloon Ablation in Treating Non-ampullary Non-polypoid Duodenal Adenomas (DAs) as Assessed by Participants With Adverse Events
Time Frame: 1 year
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
Participants With Complete Eradication of DA
Time Frame: 1 year
Complete eradication (CE) rate of DAs as assessed by a combination of endoscopic and pathologic absence of adenomatous tissue in treated areas.
Secondary Outcomes
- Percent change in the treated duodenal adenoma size(Baseline, 1 year, 2 years, 3 years, 4 years, 5 years)
- Technical failure rate(5 years)
- Change in Spigelman class score(Baseline, 1 year, 2 years, 3 years, 4 years, 5 years)
- Progression rate to high grade dysplasia or duodenal cancer(5 years)
- Time to complete eradication of DAs in each patient(5 years)
- Median number of CryoBalloon treatments to complete eradication.(5 years)
- Time to complete eradication of each treated DA lesion(5 years)
- Technical Failure Rate(1 year)
- Progression to High Grade Dysplasia or Duodenal Cancer(1 year)
- Number of Patients With Complete Eradication of All Eligible Treated DAs at 1 Year(1 year)
- Mean Number of CryoBalloon Treatments Per Patient to Achieve Complete Eradication of DAs(1 year)
- Eligible Duodenal Adenomas Treated(1 year)