Clinical trial NCT05740189: CBAS180 De-escalation Study
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Barrett's Esophagus
Ablation Therapy
Cryotherapy
Cryoballoon Ablation
Lead sponsor: St. Antonius Hospital
Sponsor class: OTHER
Collaborators: name: Pentax Medical
First posted: 2023-02-22
Enrollment: 62
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. Flat type BE esophagus, with an indication for ablation therapy, defined as:

   1. Diagnosis of LGD or HGD in BE (confirmed by BE expert pathologist) or;
   2. Residual BE with any grade of dysplasia after endoscopic resection (by means of EMR or ESD) to treat non-flat BE, ≥6 weeks prior to enrolling the patient to this study. The ER pathology should indicate endoscopic treatment (i.e. only mucosal invasion or limited submucosal invasion (sm1), no lymphovascular infiltration, free vertical resection margins and not poorly differentiated).
2. Prague Classification Score of C≤3 and M≥1.
3. Patients should be ablation-naïve, meaning they have not undergone any previous endoscopic ablation therapy of the esophagus.
4. Older than 18 years of age at time of consent.
5. Fit for endoscopic therapy per institution's standards.
6. Provides written informed consent on the IRB-approved informed consent form.
7. Willing and able to comply with follow-up requirements.

Exclusion Criteria:

1. Esophageal stenosis preventing advancement of a therapeutic endoscope.
2. Any endoscopically visualized lesion such as ulcers, masses or nodules. Neoplastic nodules must first be treated with ER ≥6 weeks prior to planned treatment under this protocol.
3. Prior ER of \>2cm in length and/or \>50% of the esophageal lumen circumference.
4. History of locally advanced (\>sm1) esophageal cancer.
5. History of esophageal varices.
6. Prior distal esophagectomy.
7. Active esophagitis LA grade B or higher.
8. Severe medical comorbidities precluding endoscopy.
9. Uncontrolled coagulopathy.
10. Pregnant or planning to become pregnant during period of study.

Primary outcomes:
measure: Efficacy: Dose response
timeFrame: 3 months
measure: Safety: Incidence of Dose-related SAEs
timeFrame: 24hours
measure: Safety: Incidence of Dose-related SAEs
timeFrame: 7 days
measure: Safety: Incidence of Dose-related SAEs
timeFrame: 30 days
Secondary outcomes:
measure: Feasibility: technical succes
timeFrame: Directly after procedure
measure: Post-procedural pain
timeFrame: Directly after procedure
measure: Post-procedural pain
timeFrame: 24 hours
measure: Post-procedural pain
timeFrame: 7 days
measure: Post-procedural pain
timeFrame: 30 days
measure: Post-procedure dysphagia
timeFrame: Directly after procedure
measure: Post-procedure dysphagia
timeFrame: 24 hours
measure: Post-procedure dysphagia
timeFrame: 7 days
measure: Post-procedure dysphagia
timeFrame: 30 days
measure: Incidence AE and SAE
timeFrame: 30 days
measure: BE regression
timeFrame: 3 months
Other outcomes:
Locations:
city: Eindhoven
country: Netherlands
facility: Catharina Hospital
state: Noord-Brabant
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC
state: Noord-Holland
city: Nieuwegein
country: Netherlands
facility: St Antonius hospital
state: Utrecht
city: Rotterdam
country: Netherlands
facility: Erasmus MC
state: Zuid-Holland
city: Groningen
country: Netherlands
facility: UMC Groningen
city: Utrecht
country: Netherlands
facility: UMC Utrecht
Study officials:
References: