Esophageal Squamous Cell Neoplasia (ESCN)
Conditions
Brief summary
Multicenter, prospective cohort clinical trial in greater China
Interventions
DEVICERadiofrequency ablation
RFA
Sponsors
Medtronic - MITG
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
1. Patient is 18-85 years of age 2. Patient has evidence of ESCN, within the last 3 months, patient demonstrated a new diagnosis or a reconfirmed diagnosis of squamous MGIN and/or HGIN of the esophagus 3. On endoscopic examination, subject has at least one USL that measures at least 3 cm in at least one dimension and greater than ¼ of the esophageal circumference and has MGIN or HGIN on biopsy, confirmed by central pathologist 4. All lesions in the esophagus are completely flat (Paris type 0-IIb), both on WLE and Lugol's chromoendoscopy 5. The maximum allowable linear length of USL-bearing esophagus is 12 cm 6. Baseline endoscopic ultrasound (EUS) (if applicable) shows no exclusionary findings for the trial 7. Computed Tomography )CT( scan of chest and upper third of the abdomen (if applicable) shows no exclusionary findings for the trial 8. Based on the judgment of the study endoscopist, the patient is eligible for treatment, follow-up endoscopy, and biopsy as required by the protocol 9. EMR or ESD occurred \> 3 months before enrollment, patients may be eligible for the study if procedure was curative (negative margins and no risk of lymph node involvement) and the patient has no other findings concerning for cancer 10. The subject is willing to provide written, informed consent to participate in this clinical study and understands the responsibilities of trial participation
Exclusion criteria
1. Patient has esophageal squamous cell carcinoma (ESCC) 2. Any non-flat (Paris type 0-I, 0-IIa, 0-IIc, 0-III) abnormalities anywhere in the esophagus 3. Any abnormalities under WLE, Lugol's chromoendoscopy or NBI that are suspicious for ESCC anywhere in the esophagus (e.g. 'pink sign' USL, defined as a color change after Lugol's staining: initially whitish yellow and pink 2-3 minutes later) 4. Any USL with MGIN or worse on biopsy outside the treatment area 5. Esophageal stricture preventing passage of a therapeutic endoscope 6. Prior endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) which occurred \< 3 months before enrollment 7. Any esophageal dilation in the past 12 months 8. Any history of a non-squamous cell cancer of the esophagus, or any history of a squamous cell cancer of the esophagus (any stage) 9. 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 10. Previous esophageal surgery, except fundoplication without complications (i.e., no slippage, dysphagia, etc.) 11. Evidence of esophageal varices detected within last 6 months or at initial RFA procedure 12. Patient has active reflux esophagitis grade C or D 13. Evidence of eosinophilic esophagitis on endoscopy and/or histology 14. Inner diameter of the esophagus measuring \<18 mm 15. 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) 16. Patient is using anti-thrombotic agents that cannot be discontinued 7 days before and after therapeutic sessions 17. Patient has an implantable pacing device (examples: automated implantable cardioverter defibrillator, neurostimulator, cardiac pacemaker) and has not received clearance for enrollment in this study by specialist responsible for the pacing device 18. Patient has life expectancy less than 5 years 19. Patient suffers from psychiatric or other illness and/or 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 20. Patient is considered to be part of a vulnerable population (e.g. prisoners or those without sufficient mental capacity) 21. The subject has participated in an investigational drug or device research study within 30 days of enrollment that would interfere with this study 22. Patient is pregnant or 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 to be eligible)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects With Complete Response (CR) | 12 month | The primary endpoint is the percentage of subjects with complete response (CR), defined as complete eradication of squamous histological abnormalities (MGIN or worse) within the treatment area (TA) at 12 months after the initial treatment session |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete Response at Three Months | 3 Months | Number of patients with a CR after primary RFA, defined as absence of MGIN or worse in any of the biopsies from the treatment area at the three months visit |
| Complete Response Within the Treatment Area | 3, 6 and 12 Month | Number of patients demonstrating complete response within the treatment area (TA), defined as detection of ESCC in biopsy or resection specimen at any time within the first 12 months. |
| Disease Progression Outside the Treatment Area | Initial, 3, 6, 9 and 12 month | Proportion of patients demonstrating MGIN or worse outside the TA during treatment phase or follow-up |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Radiofrequency Ablation Step-wise endoscopic RFA with the Barrx™ Flex Radiofrequency Ablation System using will be performed in 3 month intervals up to 12 months.
Radiofrequency ablation: RFA | 34 |
| Total | 34 |
Baseline characteristics
| Characteristic | Radiofrequency Ablation |
|---|---|
| Age, Continuous | 62.41 years STANDARD_DEVIATION 8.03 |
| Height (cm) | 162.88 cm STANDARD_DEVIATION 7.79 |
| Race/Ethnicity, Customized Chinese | 34 Participants |
| Sex: Female, Male Female | 16 Participants |
| Sex: Female, Male Male | 18 Participants |
| Weight (kg) | 64.93 kg STANDARD_DEVIATION 10.3 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 34 |
| other Total, other adverse events | 1 / 34 |
| serious Total, serious adverse events | 3 / 34 |
Outcome results
Primary
Percentage of Subjects With Complete Response (CR)
The primary endpoint is the percentage of subjects with complete response (CR), defined as complete eradication of squamous histological abnormalities (MGIN or worse) within the treatment area (TA) at 12 months after the initial treatment session
Time frame: 12 month
Population: As the study was terminated early, only 8 subjects completed 12 month follow up.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Radiofrequency Ablation | Percentage of Subjects With Complete Response (CR) | 8 Participants |
Secondary
Complete Response at Three Months
Number of patients with a CR after primary RFA, defined as absence of MGIN or worse in any of the biopsies from the treatment area at the three months visit
Time frame: 3 Months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Radiofrequency Ablation | Complete Response at Three Months | 5 Participants |
Secondary
Complete Response Within the Treatment Area
Number of patients demonstrating complete response within the treatment area (TA), defined as detection of ESCC in biopsy or resection specimen at any time within the first 12 months.
Time frame: 3, 6 and 12 Month
Population: Not all patients in the study were followed for the duration of the treatment phase of 12 months due to study termination. Therefore, primary and secondary endpoint data sample size may vary based on how many visits each subject completed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Radiofrequency Ablation | Complete Response Within the Treatment Area | 3 Month Complete Response | 5 Participants |
| Radiofrequency Ablation | Complete Response Within the Treatment Area | 6 Month Complete Response | 22 Participants |
| Radiofrequency Ablation | Complete Response Within the Treatment Area | 12 Month Complete Response | 14 Participants |
Secondary
Disease Progression Outside the Treatment Area
Proportion of patients demonstrating MGIN or worse outside the TA during treatment phase or follow-up
Time frame: Initial, 3, 6, 9 and 12 month
Population: Not all patients in the study were followed for the duration of the treatment phase of 12 months due to study termination. Therefore, primary and secondary endpoint data sample size may vary based on how many visits each subject completed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Radiofrequency Ablation | Disease Progression Outside the Treatment Area | Primary RFA | 1 Participants |
| Radiofrequency Ablation | Disease Progression Outside the Treatment Area | 3-Month | 9 Participants |
| Radiofrequency Ablation | Disease Progression Outside the Treatment Area | 6-Month | 6 Participants |
| Radiofrequency Ablation | Disease Progression Outside the Treatment Area | 9-Month | 4 Participants |
| Radiofrequency Ablation | Disease Progression Outside the Treatment Area | 12-Month | 1 Participants |