Endoscopic Ultrasound-guided RadioFrequency Ablation for the Treatment Pancreatic NeuroEndocrine Neoplasms (RAPNEN)
Primary Purpose
Neuroendocrine Tumors, Neuroendocrine Carcinoma, Pancreas Neoplasm
Status
Recruiting
Phase
Not Applicable
Locations
Italy
Study Type
Interventional
Intervention
EUS guided radiofrequency ablation
Sponsored by
About this trial
This is an interventional treatment trial for Neuroendocrine Tumors
Eligibility Criteria
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
Sites / Locations
- Fondazione Policlinico Universitario Agostino Gemelli
- Universita' del Sacro CuoreRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
EUS guided radiofrequency ablation
Arm Description
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.
Outcomes
Primary Outcome Measures
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).
Secondary Outcome Measures
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
Full Information
NCT ID
NCT03834701
First Posted
February 4, 2019
Last Updated
February 10, 2022
Sponsor
Catholic University of the Sacred Heart
1. Study Identification
Unique Protocol Identification Number
NCT03834701
Brief Title
Endoscopic Ultrasound-guided RadioFrequency Ablation for the Treatment Pancreatic NeuroEndocrine Neoplasms
Acronym
RAPNEN
Official Title
Safety and Efficacy of Endoscopic Ultrasound-guided RadioFrequency Ablation for the Treatment of Functional and Non-functional Pancreatic NeuroEndocrine Neoplasms: A Multicenter Prospective Study
Study Type
Interventional
2. Study Status
Record Verification Date
February 2022
Overall Recruitment Status
Recruiting
Study Start Date
September 1, 2019 (Actual)
Primary Completion Date
June 1, 2023 (Anticipated)
Study Completion Date
June 1, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Catholic University of the Sacred Heart
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neuroendocrine Tumors, Neuroendocrine Carcinoma, Pancreas Neoplasm, Neuroendocrine Tumor Gastrointestinal, Hormone-Secreting
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
70 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
EUS guided radiofrequency ablation
Arm Type
Experimental
Arm Description
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.
Intervention Type
Device
Intervention Name(s)
EUS guided radiofrequency ablation
Intervention Description
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.
Primary Outcome Measure Information:
Title
Incidence of adverse events (AEs) after EUS-guided radiofrequency ablation (RFA)
Description
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).
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Rates of secondary surgery
Description
Number of patients who will require secondary surgey due to adverse events occurence, no response/failed or partial/recurrence outcome to the RFA treatment
Time Frame
1 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Alberto Larghi, PhD
Phone
+390630156580
Email
alberto.larghi@yahoo.it
First Name & Middle Initial & Last Name or Official Title & Degree
Carolina Gualtieri
Phone
+390630156580
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alberto Larghi, PhD
Organizational Affiliation
Fondazione Policlinico Universitario Agostino Gemelli
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fondazione Policlinico Universitario Agostino Gemelli
City
Roma
State/Province
RM
ZIP/Postal Code
00168
Country
Italy
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Carolina Gualtieri
Phone
00390630156580
Email
carolina.gualtieri@policlinicogemelli.it
Facility Name
Universita' del Sacro Cuore
City
Rome
ZIP/Postal Code
00136
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alberto Larghi, MD
Phone
+390630156580
Email
albertolarghi@yahoo.it
12. IPD Sharing Statement
Citations:
PubMed Identifier
31058975
Citation
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.
Results Reference
derived
Learn more about this trial
Endoscopic Ultrasound-guided RadioFrequency Ablation for the Treatment Pancreatic NeuroEndocrine Neoplasms
We'll reach out to this number within 24 hrs