CryoBalloon Ablation for Barrett's Esophagus

(NO FEAR-BE Trial)

Not currently recruiting at 13 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

What You Need to Know Before You Apply

What is the purpose of this trial?

The trial aims to test a new treatment called the CryoBalloon Focal Ablation System for individuals with Barrett's Esophagus who haven't fully responded to other treatments. Barrett's Esophagus is a condition where the esophageal lining changes and can lead to cancer. The trial seeks to determine if this new method can safely and effectively treat the condition in those who have already tried radiofrequency ablation, a heat-based treatment, but still have areas of concern. Individuals with Barrett's Esophagus with dysplasia (abnormal cells) who have undergone at least two prior treatments might be suitable candidates for this study. As an unphased trial, this study offers a unique opportunity to explore a promising treatment option for those seeking alternatives.

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 prior data suggests that the CryoBalloon Focal Ablation System is safe for treating Barrett's Esophagus?

Research has shown that the CryoBalloon Focal Ablation System (CbFAS) is generally safe for treating Barrett's Esophagus. A multi-center study found that patients tolerated the treatment well and experienced positive outcomes. Another study from the UK supported these findings, demonstrating similar safety and effectiveness, consistent with larger studies. These studies indicate that while the treatment remains experimental, it has been used safely in many patients without major issues. Always discuss potential risks and benefits with your doctor before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for Barrett's Esophagus, which often involve endoscopic mucosal resection or radiofrequency ablation, the CryoBalloon Focal Ablation System (CbFAS) uses a unique cryotherapy approach. This system delivers extreme cold directly to the affected tissue through a balloon catheter, which can precisely target and eliminate abnormal cells in the esophagus. Researchers are excited about this because it potentially offers a more controlled and less invasive method of treatment, minimizing damage to surrounding healthy tissue and possibly reducing recovery time and side effects.

What evidence suggests that the CryoBalloon Ablation System is effective for Barrett's Esophagus?

Research has shown that the CryoBalloon Focal Ablation System, which participants in this trial will receive, effectively treats Barrett's Esophagus (BE). A recent study found that using the CryoBalloon for just 10 seconds can completely remove BE. Other studies confirm that this system is safe and effective for treating this condition. Patients in these studies experienced positive results, with significant improvements in eliminating BE. These findings suggest that the CryoBalloon is a promising option for those dealing with persistent BE. ^{2 3 5 6 7}

Who Is on the Research Team?

Nicholas J Shaheeen, MD, MPH

Principal Investigator

UNC Chapel Hill

Are You a Good Fit for This Trial?

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

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

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

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

Timeline for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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 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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/27997963/

Efficacy of the CryoBalloon Focal Ablation System for ... A recent dosimetry study, using the CryoBalloon Focal Ablation System (CryoBalloon), demonstrated that 10-second ablations result in complete eradication of BE.

2. sciencedirect.com sciencedirect.com/science/article/pii/S0016510722017680

Comparison of focal cryoballoon ablation with 10- and 8- ... Focal cryoballoon ablation (FCBA) is currently being investigated for the treatment of Barrett's esophagus (BE)-related neoplasia in a European multicenter ...

3. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/33/NCT02534233/Prot_SAP_000.pdf

CryoBalloon Focal Ablation System Study C2 Therapeutics, Inc. Preliminary results show the full-circumferential system is safe and has good efficacy on the ... Barrett's Esophagus. Through evaluation of the ... outcomes with ...

4. gut.bmj.com gut.bmj.com/content/74/Suppl_1/A36

O56 Clinical evaluation of cryoballoon ablation for barrett's ... Conclusions These results from the UK cryoablation registry suggest that CbFA is a safe and effective treatment for BE-D and mirror findings from larger ...

5. journals.lww.com journals.lww.com/ajg/fulltext/2020/11000/multifocal_cryoballoon_ablation_for_eradication_of.23.aspx

Multifocal Cryoballoon Ablation for Eradication of Barrett's ... In patients with neoplastic BE, CBA was safe and effective. Head-to-head comparisons between CBA and other ablation modalities are warranted.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11394299/

Efficacy and Safety of Cryoablation in Barrett's Esophagus ... Conclusions: Cryoablation provides equal outcomes compared to RFA in the treatment of patients with BE, with the cryoballoon achieving ...

7. accessdata.fda.gov accessdata.fda.gov/cdrh_docs/pdf24/K240457.pdf

July 24, 2024 PENTAX of America, Inc. Gurvinder Singh ... A multi-center retrospective study evaluated the C2 CryoBalloon ablation system focal for the treatment and management of GAVE. 28 subjects ...