C2 CryoBalloon™ 180 Ablation System Dose Escalation Study.

Study Overview
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Brief Summary
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The primary objective is to determine the safety, performance and efficacy of the C2 CryoBalloon 180 Ablation System (CryoBalloon 180) used at increasing 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
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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 6 patients will be treated with Dose 1 (lowest), in one application to ablate 50% of the esophageal circumference. All patients will undergo 8 week (±2 weeks) follow-up EGD to evaluate efficacy of the dose before the study continues. If follow-up shows that Dose 1 eradicates ≥80% of the treated BE (by median percentage) and no SAE's are reported, this dose is defined as the therapeutic dose and enrollment will proceed to phase II. If Dose 1 eradicates <80% of the treated BE, enrollment in Phase I will continue at the next higher dose (Second Dose). Treatment doses will be escalated in this manner until the first of the therapeutic doses (based on endoscopic exam) is determined, or the incidence of a dose-related Serious Adverse Event (SAE). When the therapeutic dose is determined, the study will proceed to Phase II to generate additional safety and efficacy data. --------------------------------------------------------------- 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.

Official Title
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Clinical Trial To Evaluate Safety and Dose Response Using the C2 CyroBalloon™ 180 Ablation System for the Treatment of Dysplastic Barrett's Esophagus.

Conditions
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Barrett Esophagus

Intervention / Treatment
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* Device: C2 CryoBalloon 180° Ablation System


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Prague Classification Score C≤3 and ≥M1 Patients should be ablation-naïve (no previous ablation therapy of the esophagus) Older than 18 years of age at time of consent Operable per institution's standards Patient provides written informed consent on the IRB-approved informed consent form Patient is willing and able to comply with follow-up requirements. Exclusion Criteria: Esophageal stenosis preventing advancement of a therapeutic endoscope 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. Prior ER of more than 2cm in length or >50% of the esophageal lumen circumference History of locally advanced (>SM1) esophageal cancer History of esophageal varices Prior distal esophagectomy Active esophagitis LA grade B or higher Severe medical comorbidities precluding endoscopy Uncontrolled coagulopathy Pregnant or planning to become pregnant during period of study Patient refuses or is unable to provide written informed consent Participation in another study with investigational drug within the 30 days preceding or during the present study, interfering with participation in the current study General poor health, multiple co-morbidities placing the patient at risk or otherwise unsuitable for trial participation

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Patients with previously untreated (by means of ablation therapy) flat type Barrett's Esophagus (BE) (extent BE ≤C3 and ≥M1) with Low-Grade Dysplasia (LGD) or High-Grade Dysplasia (HGD), or residual BE after endoscopic resection of dysplasia or early adenocarcinoma.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: C2 CryoBalloon 180 Ablation System<br>C2 CryoBalloon 180 Ablation System will be used to ablate visible Barrett's esophagus | Device: C2 CryoBalloon 180° Ablation System<br>* The C2 CryoBalloon 180° Ablation System is a cryosurgical device with a nitrous oxide cooled balloon probe that is compatible with upper gastrointestinal therapeutic endoscopes.<br>* Other names: CryoBalloon 180;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: Incidence of Dose-related SAEs | 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. | 30 days | 
| Efficacy: Dose response | 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). | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of AEs | Incidence of all serious and non-serious adverse events up to 30 days post-treatment | 30 days | 
| Pain | Post-procedure pain in the area of the cryoablation treatment (0-10 VAS score) | 24hours and 7 days post-procedure | 
| Efficacy: Percent Regression | 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. | 8 weeks | 
| Efficacy: Treatment | 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. | 8 weeks |