C2 CryoBalloon™ 180 Ablation System Dose De-escalation Study.

Not Applicable

• Conditions: Barrett Esophagus
• Interventions: Device: C2 CryoBalloon 180° Ablation System

• Registration Number: NCT03311451
• Lead Sponsor: Pentax Medical

Brief Summary

The primary objective is to determine the safety, performance and efficacy of the C2 CryoBalloon 180 Ablation System ("CryoBalloon 180") used at decreasing doses in treatment naïve patients with low- or high-grade dysplastic Barrett's Esophagus (BE) or with residual BE after resection of dysplasia or early adenocarcinoma.

Detailed Description

The procedure will be performed on an outpatient basis, and the CryoBalloon 180 Ablation system will be used for all ablations following the instructions for use provided with the product.

Patients who meet the eligibility criteria will be assigned to one of the treatment groups and doses, depending on the order of their enrollment:

In phase I, the first 25 patients will be treated with Dose 1 (lowest), in one application to ablate 50% of the esophageal circumference.

All patients will undergo 10 week (±2 weeks) follow-up EGD to evaluate efficacy of the dose before the study continues.

If follow-up shows that Dose 1 eradicates ≤60% of the treated BE (by median percentage) and no SAE's are reported, the treatment phase will continue but at the next incremental higer dose (Second Dose) after approval from the IRB.

If the Dose 1 median BE surface regression percentage is ≥60%, the dose is defined as the therapeutic dose. In that case, an additional group of 25 patients will be enrolled at this dose, pending IRB approval.

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Dose-related SAEs include pain in the treatment area greater than 6 (0-10 VAS score) at 24 hours AND seven (7) days post-treatment; symptomatic stricture requiring an additional EGD with endoscopic dilation before the first follow-up EGD; symptomatic stricture at follow-up EGD; or any stricture (symptomatic or asymptomatic) preventing passage of the therapeutic endoscope at follow-up EGD. Any other serious adverse events within 30 days after treatment will also be evaluated by the Data and Safety Monitoring Board (DSMB) for relationship to the dose and severity.

When a Dose-related serious adverse event occurs, the Holding Rule will be invoked and enrollment at that dose will be held until the DSMB has evaluated the event.

Study Timeline

• Study First Submitted: 2017-10-10
• Study First Submitted QC: 2017-10-13
• Study First Posted: 2017-10-17
• Study Start: 2023-01-16
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-09
• Last Update Posted: 2025-01-13
• Primary Completion: 2025-08-01
• Study Completion: 2026-12-01

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

1. Patients with flat- type BE esophagus, with an indication for ablation therapy, defined as:

   • Diagnosis of LGD or HGD in BE (confirmed by central pathology review), OR
   • Residual BE with any grade of dysplasia 6 weeks after endoscopic resection

2. Prague Classification Score C≤3 and ≥M1

3. Patients should be ablation-naïve (no previous ablation therapy of the esophagus)

4. Older than 18 years of age at time of consent

5. Operable per institution's standards

6. Patient provides written informed consent on the IRB-approved informed consent form

7. Patient is 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 more than 2cm in length 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
11. Patient refuses or is unable to provide written informed consent
12. Participation in another study with investigational drug within the 30 days preceding or during the present study, interfering with participation in the current study
13. General poor health, multiple co-morbidities placing the patient at risk or otherwise unsuitable for trial participation

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
C2 CryoBalloon 180 Ablation System	C2 CryoBalloon 180° Ablation System	C2 CryoBalloon 180 Ablation System will be used to ablate visible Barrett's esophagus

Primary Outcome Measures

Name	Time	Method
Safety: Incidence of Dose-related SAEs	30 days	Safety will be evaluated by the incidence of Dose-related SAEs.; Dose-related SAEs include pain in the treatment area, or any stricture (symptomatic or asymptomatic) preventing passage of the diagnostic endoscope at follow-up EGD.
Efficacy: Dose response	10 weeks	Dose response (efficacy) is defined as eradication percentage of BE confirmed by histological evidence of eradication of BE, after treatment with the therapeutic dose (phase II).

Secondary Outcome Measures

Name	Time	Method
Incidence of AEs	30 days	Incidence of all serious and non-serious adverse events up to 30 days post-treatment
Efficacy: Treatment	10 weeks	Efficacy of treatment with CryoBalloon 180 Ablation system, defined as the proportion of patients with ≥80% regression of BE after 1 hemi-circumferential and after full circumferential treatment.
Patient reported post-procedure pain	24hours and 7 days post-procedure	Post-procedure pain in the area of the cryoablation treatment (0-10 VAS score)
Efficacy: Percent Regression	10 weeks	Efficacy, defined as the regression percentage at the first follow-up endoscopy, after one (1) treatment covering 50% of circumference of the esophagus with the therapeutic dose.

Trial Locations

Locations (5)

AMC Medical Research B.V.; 🇳🇱 Amsterdam, Netherlands

St. Antonius Hospital; 🇳🇱 Nieuwegein, Netherlands

UMC Groningen; 🇳🇱 Groningen, Netherlands

Erasmus Medical Center; 🇳🇱 Rotterdam, Netherlands

UMC Utrecht; 🇳🇱 Utrecht, Netherlands