CryoBalloon Ablation for Barrett's Esophagus

(NO FEAR-BE Trial)

Recruiting at 11 trial locations

Overseen By Susan Moist, MPH

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of North Carolina, Chapel Hill

Must not be taking: Anticoagulants, Antiplatelets

Disqualifiers: Severe comorbidities, Esophageal malignancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

Duration: Up to 12 months

70 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial requires participants to stop using anti-coagulation medications or non-aspirin anti-platelet agents for a certain period, as recommended for high-risk endoscopy procedures. Other medications are not specifically mentioned, so it's best to discuss with the trial team.

What data supports the effectiveness of the CryoBalloon Ablation treatment for Barrett's Esophagus?

Research shows that the CryoBalloon Ablation treatment is effective in completely eradicating Barrett's Esophagus (BE) in targeted areas, with a study reporting 100% success in removing abnormal tissue in treated areas. Additionally, the treatment is considered safe and precise, with no significant complications observed. ^{1 2 3 4 5}

Is CryoBalloon Ablation safe for humans?

Research shows that the CryoBalloon Ablation System is generally safe for treating Barrett's esophagus and other esophageal conditions. Studies have found it to be feasible and safe in both human and animal models, with no major safety concerns reported. ^{2 3 4 5 6}

How is the CryoBalloon Ablation System treatment different from other treatments for Barrett's Esophagus?

The CryoBalloon Ablation System is unique because it uses cold energy to target and eradicate Barrett's Esophagus tissue, offering precise targeting and the ability to treat larger areas in a single step. Unlike other treatments like radiofrequency ablation, it does not require complex sizing or multiple deployment steps, making it simpler and potentially more efficient. ^{1 3 4 5 6}

Research Team

Nicholas J Shaheeen, MD, MPH

Principal Investigator

UNC Chapel Hill

Eligibility Criteria

This trial is for adults who've had at least 2-3 unsuccessful radiofrequency ablations to treat Barrett's Esophagus with dysplasia or intestinal metaplasia. Candidates should not have used certain esophageal treatments before, must be in good health overall, and willing to follow the study plan.

Inclusion Criteria

Provides written informed consent.

I have abnormal cell growth in my esophagus.

I have Barrett's esophagus with confirmed low or high-grade dysplasia, or treated early-stage cancer with low risk of coming back.

Exclusion Criteria

I have or had high blood pressure in the liver or swollen veins in my esophagus.

Pregnant or planning to become pregnant during period of study participation.

My esophagus was narrow but has been widened to at least 15mm.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Cryoballoon Focal Ablation System (CbFAS) treatment every 3 months +/- 6 weeks for up to 12 months or until complete eradication of intestinal metaplasia (CEIM) and dysplasia (CED) are achieved

Up to 12 months

Every 3 months +/- 6 weeks

Follow-up

Participants are monitored for safety and effectiveness after achieving CEIM and CED, with follow-up visits at 3, 6, 9, and 12 months depending on baseline condition

12 months

3, 6, 9, and 12 months (for HGD or IMC); 6 and 12 months (for LGD)

Treatment Details

Interventions

• CryoBalloon Focal Ablation System

Trial Overview The NO FEAR-BE trial tests the C2 CryoBalloon Focal Ablation System's safety and effectiveness on patients whose Barrett's Esophagus hasn't improved after multiple radiofrequency ablations. It’s a single-group study without randomization.

Participant Groups

Group I: Cryoballoon Focal Ablation System (CbFAS) Treatment Experimental Treatment 1 Intervention

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

CryoBalloon Focal Ablation System is already approved in European Union, United States, China for the following indications:

Approved in European Union as C2 CryoBalloon Ablation System for:

• Ablation of unwanted tissue in the gastrointestinal tract, including treatment of Barrett’s Esophagus and squamous dysplasia with application of extreme cold

Approved in United States as C2 CryoBalloon Ablation System for:

• Ablation of Barrett’s esophagus with dysplasia

Approved in China as C2 CryoBalloon Ablation System for:

• Treatment of Esophageal Squamous Cell Neoplasia (ESCN)

Who Is Running the Clinical Trial?

University of North Carolina, Chapel Hill

Lead Sponsor

Trials

1,588

Recruited

4,364,000+

PENTAX of America, Inc.

Collaborator

Trials

1

Recruited

70+

Johns Hopkins University

Collaborator

Trials

2,366

Recruited

15,160,000+

Findings from Research

In a study involving 30 patients with Barrett's esophagus, a 10-second cryoablation using the CryoBalloon successfully targeted 94% of the BE islands, demonstrating effective treatment precision.

Complete eradication of intestinal metaplasia and dysplasia was achieved in all areas that were completely ablated, with no reported complications such as stenoses, indicating a safe and effective intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of the CryoBalloon Focal Ablation System for the eradication of dysplastic Barrett's esophagus islands. Künzli, HT., Schölvinck, DW., Meijer, SL., et al.[2018]

In a study involving 80 patients with esophageal squamous cell neoplasia, the cryoballoon focal ablation system (CbFAS) demonstrated a high efficacy rate, achieving complete response in 97% of patients after 12 months, indicating its effectiveness for treating this condition.

The CbFAS was found to be safe and well tolerated, with no serious adverse events reported, and only minor self-limiting mucosal lacerations occurring in a few patients, suggesting it is a promising alternative to traditional treatments like EMR and ESD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective study of endoscopic focal cryoballoon ablation for esophageal squamous cell neoplasia in China. Ke, Y., van Munster, SN., Xue, L., et al.[2021]

The study demonstrated that combining endoscopic resection (ER) with the Cryoballoon focal ablation system (CbFAS) is technically feasible in porcine models, indicating potential for effective treatment of dysplastic Barrett's esophagus.

No significant tissue damage differences were observed between CbFAS alone and the combination therapy, suggesting that the combination does not increase risks of complications such as bleeding or perforation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endoscopic resection combined with the Cryoballoon focal ablation system in the porcine normal esophagus: a preclinical study. Sunakawa, H., Yoda, Y., Takeshita, N., et al.[2021]

The Cryoballoon Focal Ablation System (CbFAS) is a safe and feasible method for treating Barrett's epithelium, with no major adverse events reported and only minor complications observed in a study of 39 patients.

The treatment resulted in full squamous regeneration in 82% of areas treated with 8 seconds of ablation and 100% in areas treated with 10 seconds, indicating effective dose response and potential for successful outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Barrett's esophagus with a novel focal cryoablation device: a safety and feasibility study. Schölvinck, DW., Künzli, HT., Kestens, C., et al.[2022]

The novel 90°-swipe cryoballoon ablation system (CbSAS90) demonstrated a high technical success rate of 92% in treating dysplastic Barrett's esophagus (BE) in a study of 25 patients, indicating its feasibility and effectiveness for ablating larger areas.

The treatment resulted in significant BE surface regression, with a median of 85% regression at the effective dose, while post-procedural pain and dysphagia were low, suggesting a favorable safety profile, although further evaluation is needed to optimize the balance between safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel cryoballoon ablation system for eradication of dysplastic Barrett's esophagus: a first-in-human feasibility study. van Munster, SN., Overwater, A., Raicu, MGM., et al.[2021]

In a study of 311 patients with dysplastic Barrett's esophagus, both cryoballoon ablation (CBA) and radiofrequency ablation (RFA) showed similar effectiveness in achieving complete remission of intestinal metaplasia and dysplasia, indicating that both methods are viable options for endoscopic eradication therapy.

However, CBA was associated with a higher rate of strictures (10.4%) compared to RFA (4.4%), suggesting that while both techniques are effective, CBA may carry a greater risk of complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative outcomes of radiofrequency ablation and cryoballoon ablation in dysplastic Barrett's esophagus: a propensity score-matched cohort study. Agarwal, S., Alshelleh, M., Scott, J., et al.[2022]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Efficacy of the CryoBalloon Focal Ablation System for the eradication of dysplastic Barrett's esophagus islands. [2018]

2. United States pubmed.ncbi.nlm.nih.gov

Prospective study of endoscopic focal cryoballoon ablation for esophageal squamous cell neoplasia in China. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Endoscopic resection combined with the Cryoballoon focal ablation system in the porcine normal esophagus: a preclinical study. [2021]

4. Germany pubmed.ncbi.nlm.nih.gov

Treatment of Barrett's esophagus with a novel focal cryoablation device: a safety and feasibility study. [2022]

5. Germany pubmed.ncbi.nlm.nih.gov

A novel cryoballoon ablation system for eradication of dysplastic Barrett's esophagus: a first-in-human feasibility study. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Comparative outcomes of radiofrequency ablation and cryoballoon ablation in dysplastic Barrett's esophagus: a propensity score-matched cohort study. [2022]