Evaluation of Endoscopic Ultrasound-Guided Radiofrequency Ablation for the Management of Pancreatic Tumors, ERASE Study

Study Overview
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Brief Summary
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This clinical trial evaluates the safety and effectiveness of endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) for the management of patients with pancreatic tumors (including cysts) performed during recommended surveillance endoscopic ultrasound examinations. Pancreatic tumors (cysts) can progress to pancreatic cancer at rate of more than 25% per year risk. Pancreatic cancer is a fatal disease that is difficult to diagnose at an early stage, and the five-year survival rate is currently less than 10%. It is projected to be the second leading cause of cancer-related mortality by the year 2030. A procedure known as radiofrequency ablation may help. Radiofrequency ablation is an established way to treat benign and cancerous tumors in the human body. In the last 5 years, radiofrequency ablation has been applied to treat precancerous tumors (including cysts) in the pancreas. This procedure implements a medical technology that destroys tumors in a much less invasive way compared to traditional surgical removal. By delivering a high-frequency alternating current, radiofrequency ablation uses electrical energy and heat to destroy cancer cells. Radiofrequency ablation is being recognized as a management option in patients with high-risk pancreatic tumors (cysts) but are not deemed surgical candidates. While surgical removal offers a chance of cure, pancreatic surgeries have 20-40% morbidity rate (short and long-term complication) and a 1-2% mortality rate in patients who are surgical candidates. Furthermore, radiofrequency ablation can potentially decrease the need for frequent imaging/surveillance of the pancreatic tumor (cyst). In patients with immediate prohibitive, but reversible risks for surgery, radiofrequency ablation of a high-risk tumors (cysts) can potentially prevent further progression of the lesion and bridge the time before the need for surgical resection.

Detailed Description
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PRIMARY OBJECTIVE: I. To assess the efficacy of EUS-RFA of pancreatic cystic neoplasms (PCNs). SECONDARY OBJECTIVES: I. To assess the safety of EUS-guided RFA of PCNs. II. To assess the long-term response to EUS-RFA. OUTLINE: Patients undergo standard of care EUS-fine-needle aspiration (FNA) followed by EUS-RFA on study and may undergo repeat EUS-RFA or EUS-guided chemoablation during surveillance. Patients undergo magnetic resonance imaging (MRI)/magnetic resonance cholangiopancreatography (MRCP), computed tomography (CT), or EUS-FNA at baseline and at follow-up timepoints. After completion of study treatment, patients are followed up every 3-6 months for cysts >= 3 cm or every 6-12 months for cysts < 3 cm for up to 3 years.

Official Title
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Endoscopic Ultrasound-Guided Radiofrequency Ablation of Pancreatic Cysts - A Safety and Efficacy Trial (ERASE Study)

Conditions
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Pancreatic Neoplasm

Intervention / Treatment
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* Procedure: Chemical Ablation
* Procedure: Computed Tomography
* Other: Electronic Health Record Review
* Procedure: Endoscopic Ultrasound-Guided Fine-Needle Aspiration
* Procedure: Endoscopic Ultrasound-Guided Radiofrequency Ablation
* Procedure: Magnetic Resonance Cholangiopancreatography
* Procedure: Magnetic Resonance Imaging


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > 18 years A diagnosis of a PCN confirmed by EUS-FNA including cyst fluid next generation sequencing (NGS) and/or EUS-guided needle-based confocal laser endomicroscopy (nCLE) and/or EUS- guided through-the-needle biopsy (TTNB) The pancreatic cystic lesion (PCL) measures at least 2 cm in diameter on either CT or MRI/MRCP or EUS and demonstrates concerning worrisome and/or high-risk features as defined by International Consensus Guidelines (2017 revised Fukuoka Guidelines) The patient is not a surgical candidate. Common clinical scenarios include - Cirrhosis of the liver (common clinical scenario) Advanced ( >= 75 years) age (common clinical scenario) Morbid obesity Significant cardiorespiratory comorbidity Patient's choice (patient elects for non-surgical management) Other significant comorbid conditions that impose prohibitive surgical risks Estimated life expectancy of at least 1 year Capable of giving written informed consent Women of childbearing potential must have a negative pregnancy test (serum/urine) on the day of treatment. Pregnancy testing is the routine standard of care practice in the endoscopy laboratory for all patients undergoing endoscopy and sedation for endoscopy The patient prefers non-surgical management after consultation with hepato-pancreato-biliary (HPB) surgery The patient is not a surgical candidate and has had prior attempts at ablation of the PCN by EUS-guided injection of chemotherapy (Ohio State University [OSU] Institutional Review Board [IRB] protocol 2020C0198) Exclusion Criteria: A diagnosis of a benign or non-neoplastic PCL such as a pseudocyst confirmed by EUS-FNA including cyst fluid NGS and/or EUS-nCLE and/or EUS-TTNB A diagnosis of a malignant PCN confirmed by evidence of adenocarcinoma and/or invasive carcinoma and/or distant metastases Cysts or neuroendocrine tumors (NETS) involving or in close proximity to blood vessels, the biliary tree, or the main pancreatic duct where the zone of ablation is likely to compromise these structures Acute pancreatitis in the preceding 4 weeks prior to date of EUS-RFA Any evidence of severe or uncontrolled systemic diseases or laboratory finding that in the view of the investigator makes it unsafe for the patient to participate in the study Any psychiatric disorder making reliable informed consent impossible Pregnancy or breast-feeding Eastern Cooperative Oncology Group (ECOG) performance status 4 Contraindication to general anesthesia after review by OSU Preoperative Assessment Clinic (OPAC) Cardiac implantable electrical devices

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: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (EUS-RFA)<br>Patients undergo standard of care EUS-FNA followed by EUS-RFA on study and may undergo repeat EUS-RFA or EUS-guided chemoablation during surveillance. Patients undergo MRI/MRCP, CT, or EUS-FNA at baseline and at follow-up timepoints. | Procedure: Chemical Ablation<br>* Undergo EUS-guided chemoablation<br>* Other names: ABLATION, CHEMICAL;Procedure: Computed Tomography<br>* Undergo CT<br>* Other names: tomography;Other: Electronic Health Record Review<br>* Ancillary studies<br>Procedure: Endoscopic Ultrasound-Guided Fine-Needle Aspiration<br>* Undergo EUS-FNA<br>* Other names: EUS-FNA;Procedure: Endoscopic Ultrasound-Guided Radiofrequency Ablation<br>* Undergo EUS-RFA<br>* Other names: EUS-RFA;Procedure: Magnetic Resonance Cholangiopancreatography<br>* Undergo MRI/MRCP<br>* Other names: MRCP;Procedure: Magnetic Resonance Imaging<br>* Undergo MRI/MRCP<br>* Other names: Nuclear Magnetic Resonance Imaging;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) | Defined as at least a 50% decrease in the cyst diameter. Other markers of response to EUS-RFA will be evaluated by cross-sectional imaging and EUS: change in the diameter, morphology of cyst - fibrosis, septations, loculations, wall thickness, intracystic or mural nodules; cyst fluid aspiration (biopsy if there is fibrosis): next generation sequencing (NGS) - persistence or absence of mutations (molecular markers), cytology - results can include either: mucin, atypical/suspicious cells, necrotic material, or inflammatory debris, experimental: flow cytometry for immunological markers of antineoplastic response; serological changes: chromogranin A (for cystic-neuroendocrine tumor), and serum cancer antigen (CA) 19-9 (if elevated prior to intervention). | At 1 years after EUS-RFA | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Long-term response to EUS-RFA | Defined as at least a 50% decrease in the cyst diameter. Durable response: Continued response with further decrease in cyst diameter beyond the first calendar year. The response will be evaluated by cross-sectional imaging and EUS: change in the diameter, morphology of cyst - fibrosis, septations, loculations, wall thickness, intracystic or mural nodules; cyst fluid aspiration (biopsy if there is fibrosis): NGS - persistence or absence of mutations (molecular markers), cytology - results can include either: mucin, atypical/suspicious cells, necrotic material, or inflammatory debris, experimental: flow cytometry for immunological markers of antineoplastic response; serological changes: chromogranin A (for cystic-neuroendocrine tumor), and serum CA 19-9 (if elevated prior to intervention). | At 2 and 3 years after EUS-RFA | 
| Safety of EUS-guided RFA of pancreatic cystic neoplasms post procedure | Documented using the adverse events in gastrointestinal endoscopy classification for adverse events in gastrointestinal advanced endoscopy. Only grade II or higher degree of complications will be documented since patients are electively admitted after EUS-RFA for overnight observation. If patient has post-procedure acute pancreatitis, document severity based on Revised Atlanta Classification. | Post-procedure (after EUS-RFA) | 
| Safety of EUS-guided RFA of pancreatic cystic neoplasms at one year | Documented using the adverse events in gastrointestinal endoscopy classification for adverse events in gastrointestinal advanced endoscopy. Only grade II or higher degree of complications will be documented since patients are electively admitted after EUS-RFA for overnight observation. If patient has post-procedure acute pancreatitis, document severity based on Revised Atlanta Classification. | at one year after EUS-RFA |