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

Clinical Trial To Evaluate Safety and Efficacy of the C2 CyroBalloon™ 180 Ablation System for the Treatment of Dysplastic Barrett's Esophagus: CBAS180 De-escalation Study

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

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 62 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 higher 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, the study will be prematurely terminated without the consecutive treatment of an additional 62 patients with a higher dose.

---------------------------------------------------------------

Dose-related SAEs include pain in the treatment area greater than 6 (0-10 NRS 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.

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 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
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