Endoscopic Ultrasound-guided RadioFrequency Ablation for the Treatment Pancreatic NeuroEndocrine Neoplasms (RAPNEN)

Safety and Efficacy of Endoscopic Ultrasound-guided RadioFrequency Ablation for the Treatment of Functional and Non-functional Pancreatic NeuroEndocrine Neoplasms: A Multicenter Prospective Study

This study evaluates the possibility and the safety of performing local therapy for Pancreatic neuroendocrine neoplasms (PanNENs) using radiofrequency ablation of the tumor under ultrasonography (EUS) guidance.

Study Overview

• Status: Completed
• Conditions: Neuroendocrine Tumors; Neuroendocrine Carcinoma; Pancreas Neoplasm; Neuroendocrine Tumor Gastrointestinal, Hormone-Secreting
• Intervention / Treatment: Device: EUS guided radiofrequency ablation

Detailed Description

Pancreatic neuroendocrine neoplasms (PanNENs) are rare, but their incidence has significantly increased in the last decades. The mainstay treatment of PanNENs is surgery, which is associated with a significant benefit in term of survival but also with significant short- and long-term adverse events.

Based on the above data, less invasive alternative therapeutic interventions to avoid short- and long-term adverse events of surgery are needed.

In this context radiofrequency ablation has been reported to be effective in the treatment of these tumors in absence of major adverse events. However, the available studies on the matter are limited by small sample size and lack of standardized criteria for patient selection.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Rome, Italy, 00136
    • Universita' del Sacro Cuore
  • RM
    • Roma, RM, Italy, 00168
      • Fondazione Policlinico Universitario Agostino Gemelli

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

For all patients

• Age ≥18 years and <80 years
• Signed written informed consent
• Distance from the main pancreatic duct ≥2mm
• Able to undergo endoscopic ultrasound examination
• Homogeneous enhancement at contrast harmonic EUS (CH-EUS)

For patients with functional pancreatic neuroendocrine neoplasms (F-PanNENs), almost all insulinomas

• Definitive diagnosis of a clinical syndrome related to excessive insulin secretion fasting test, insulin blood levels, C-peptide blood levels)
• Single lesion visualized at CT, and/or MRI, and/or EUS
• Size < 20mm

For patients with non functional pancreatic neuroendocrine neoplasms (NF-PanNENs)

• EUS fine needle biopsy (FNB) proven NF-PanNENs
• 68Ga-DOTATATE PET/CT positive for a pancreatic lesion and negative for lymph nodes, liver, and other distant metastases
• Hyper- or Iso-enhancing pattern at MRI and/or CT with negative lymph nodes, liver, and other distant metastases
• G1 or G2 ≤ 5% on histological examination of EUS-guided biopsy samples utilizing EUS-FNB needles
• Diameter between 15mm and 25mm,
• Absence of symptoms
• Absence of inner calcifications

Exclusion Criteria:

• For all patients
• Known bleeding disorder that cannot be sufficiently corrected with co-fact or fresh frozen plasma (FFP)
• Use of anticoagulants that cannot be discontinued
• INR >1.5 or platelet count <50.000
• Previous inclusion in other studies
• Pregnancy
• Minimal distance from the main pancreatic duct <1mm
• Inability to sign the informed consent
• Heterogeneous enhancement at contrast harmonic EUS (CH-EUS)

For patients with F-PanNENs (almost all insulinomas)

• Diagnosis work up negative excessive hormone secretion syndrome
• Multiple lesions visualized at CT, and/or MRI, and/or EUS
• Size > 20mm
• For patients with NF-PanNENs
• G2>5% or G3 on histological examination of EUS-guided biopsy samples
• Diameter <15 mm and >25 mm
• Presence of symptoms
• Presence of calcifications
• Hypo-enhancing pattern at MRI and/or CT
• 68Ga-DOTATATE PET/CT positive for lymph nodes, liver, and other distant metastasis
• Diagnosis on multiple endocrine neoplasia type 1 (MEN1) syndrome or Von Hippel Lindau syndrome
• Previous inclusion in other studies

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: EUS guided radiofrequency ablation; Radiofrequency ablation will be performed using a system that consists of an 19-gauge needle electrode (140-cm long), a radiofrequency generator, and an inner cooling system that circulates chilled saline solution during the RFA procedure.

Device: EUS guided radiofrequency ablation; The EUS-RFA system (Taewoong, Seoul, Korea) utilized for EUS-RFA consists of an 19-gauge needle electrode (140-cm long), a radiofrequency generator, and an inner cooling system that circulates chilled saline solution during the RFA procedure. The inner metal part is insulated over its entire length, with the exception of the terminal 5 to 20mm for energy delivery. The needle electrode is attached to a radio frequency current generator (VIVA RF generator; Taewoong) and to a cooling pump. The generator, in addition to providing radio frequency current, allows the control of physical power and impedance parameters.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events (AEs) after EUS-guided radiofrequency ablation (RFA)	AEs will be classified as procedural when they occur during the procedure; post-procedural when they will occur up to 14 days after the procedure; late when they will occur more than 14 days after the procedure. Minor AEs will be those that need no therapy and have no sequelae (A) or have minor therapy or consequence, including overnight admission (B). Major events include those that require major therapy or hospitalization (24- 48 hours) (C); major therapy, need unplanned increase in level of care, or hospitalization >48 hours (D); or result in permanent adverse sequelae (E) and death (F).	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rates of secondary surgery	Number of patients who will require secondary surgey due to adverse events occurence, no response/failed or partial/recurrence outcome to the RFA treatment	1 year

Collaborators and Investigators

• Sponsor: Catholic University of the Sacred Heart
• Investigators: Principal Investigator: Alberto Larghi, PhD, Fondazione Policlinico Universitario Agostino Gemelli

Publications and helpful links

General Publications

• Hofland J, de Herder WW, Kann PH. Turning Up the Heat: Endoscopic Ablation of Pancreatic Neuroendocrine Neoplasms. J Clin Endocrinol Metab. 2019 Nov 1;104(11):5053-5055. doi: 10.1210/jc.2019-00954. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2019
• Primary Completion (Actual): January 1, 2024
• Study Completion (Actual): February 1, 2024

Study Registration Dates

• First Submitted: February 4, 2019
• First Submitted That Met QC Criteria: February 6, 2019
• First Posted (Actual): February 8, 2019

Study Record Updates

• Last Update Posted (Estimated): February 13, 2024
• Last Update Submitted That Met QC Criteria: February 12, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Pancreatic Diseases; Neoplasms; Pancreatic Neoplasms; Carcinoma, Neuroendocrine; Neuroendocrine Tumors
• Other Study ID Numbers: RAPNEN

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No