Radiofrequency Ablation for Patients With Esophageal Squamous Cell Neoplasia

A Single-center Trial of Endoscopic Radiofrequency Ablation of Moderate and High-grade Intra-epithelial Squamous Neoplasia and Early Flat-type Squamous Cell Carcinoma Using the HALO Ablation System

Patients with MGIN, HGIN or flat-type early SCCA of the esophagus will be treated on 3 month intervals with Radiofrequency Ablation (RFA) until complete eradication (CR: no MGIN or worse in the biopsies) will be achieved. All patients will undergo an endoscopy at 12 months after baseline, and the patients with CR will undergo annual endoscopy with biopsies for 5 years.

A patient population with a histopathological diagnosis of moderate-grade intra-epithelial neoplasia (MGIN), high-grade intra-epithelial neoplasia (HGIN) and/or early flat-type SCCA of the esophagus, in lesions measuring 3 to 12cm in length, will be treated with radiofrequency ablation (RFA) using the HALO ablation system. Additional RFA sessions will be performed on 3 month intervals until complete response (CR; no MGIN or worse in biopsies) will be achieved. All patients will then undergo an endoscopy at 12 months after baseline. Patients with CR at 12 months will be followed-up for 5 years with annual endoscopy and biopsies, and additional treatment if necessary. Patients with no CR at 12 months are considered failures.

Inclusion Criteria:

1. Subject is 18-80 years of age, inclusive

2. Subject meets at least one of the following inclusion criteria:

   1. Within the last 3 months, subject demonstrated a new diagnosis or a reconfirmed diagnosis of squamous MGIN and/or HGIN of the esophagus, or...
   2. within the last 3 months, subject demonstrated a new diagnosis of a flat-type (type 0-IIb) SCCA (G1/G2 only)

3. On endoscopic examination, subject has at least one USL that measures at least 3 cm in at least one dimension and has MGIN or worse (MGIN+) on biopsy

4. The maximum allowable linear length of "USL-bearing esophagus" is 12 cm

5. Baseline EUS (all patients) shows no exclusionary findings for the trial

6. CT scan of chest and upper third of the abdomen (all HGIN and SCCA patients) shows no exclusionary findings for the trial

7. Subject is not pregnant nor has plans to become pregnant in the ensuing 12 months (confirmation of non-pregnant status in women of child-bearing age and ability required with urine or blood test)

8. Subject is eligible for treatment and follow-up endoscopy and biopsy as required by the protocol

9. The subject is willing to provide written, informed consent to participate in this clinical study and understands the responsibilities of trial participation

Exclusion Criteria:

the Eligibility CRF.

1. Esophageal stricture preventing passage of a therapeutic endoscope
2. Any prior endoscopic resection
3. Any esophageal dilation in the past 12 months
4. Any history of a non-squamous cell cancer of the esophagus, or any history of a squamous cell cancer of the esophagus (any stage) prior to 3 months before screening for this trial
5. Any N or M positive status, if patient has a present diagnosis of esophageal SCCA
6. Any previous ablative therapy within the esophagus (photodynamic therapy, multipolar electrical coagulation, argon plasma coagulation, laser treatment, or other) or any radiation therapy to the esophagus.
7. Any previous esophageal surgery, except fundoplication without complications (i.e. no slippage, dysphagia, etc)
8. Evidence of esophageal varices detected within last 6 months or at initial RFA procedure
9. Evidence of eosinophilic esophagitis on endoscopy and/or histology
10. Report of uncontrolled coagulopathy with international normalized ratio (INR) > 2 or platelet count <75,000 platelets per µL (note: a complete blood count is not required for all subjects in this study)
11. Subject is using aspirin, clopidogrel, or non-steroidal anti-inflammatory drugs that can not be discontinued 7 days before and after therapeutic sessions
12. Subject has a known history of unresolved drug or alcohol dependency that would limit ability to comprehend or follow instructions related to informed consent, post-treatment instructions, or follow-up guidelines
13. Subject has an implantable pacing device (examples; AICD, neurostimulator, cardiac pacemaker) and has not received clearance for enrollment in this study by specialist responsible for the pacing device
14. Subject suffers from psychiatric or other illness deemed by the investigator as an inability to comply with protocol
15. Subject has life expectancy less than 2 years