<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03834701</url>
  </required_header>
  <id_info>
    <org_study_id>RAPNEN</org_study_id>
    <nct_id>NCT03834701</nct_id>
  </id_info>
  <brief_title>Endoscopic Ultrasound-guided RadioFrequency Ablation for the Treatment Pancreatic NeuroEndocrine Neoplasms</brief_title>
  <acronym>RAPNEN</acronym>
  <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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Catholic University of the Sacred Heart</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Catholic University of the Sacred Heart</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study evaluates the possibility and the safety of performing local therapy for&#xD;
      Pancreatic neuroendocrine neoplasms (PanNENs) using radiofrequency ablation of the tumor&#xD;
      under ultrasonography (EUS) guidance.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Pancreatic neuroendocrine neoplasms (PanNENs) are rare, but their incidence has significantly&#xD;
      increased in the last decades. The mainstay treatment of PanNENs is surgery, which is&#xD;
      associated with a significant benefit in term of survival but also with significant short-&#xD;
      and long-term adverse events.&#xD;
&#xD;
      Based on the above data, less invasive alternative therapeutic interventions to avoid short-&#xD;
      and long-term adverse events of surgery are needed.&#xD;
&#xD;
      In this context radiofrequency ablation has been reported to be effective in the treatment of&#xD;
      these tumors in absence of major adverse events. However, the available studies on the matter&#xD;
      are limited by small sample size and lack of standardized criteria for patient selection.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">September 1, 2019</start_date>
  <completion_date type="Anticipated">June 1, 2023</completion_date>
  <primary_completion_date type="Anticipated">June 1, 2023</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of adverse events (AEs) after EUS-guided radiofrequency ablation (RFA)</measure>
    <time_frame>1 year</time_frame>
    <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 &gt;48 hours (D); or result in permanent adverse sequelae (E) and death (F).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Rates of secondary surgery</measure>
    <time_frame>1 year</time_frame>
    <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</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">70</enrollment>
  <condition>Neuroendocrine Tumors</condition>
  <condition>Neuroendocrine Carcinoma</condition>
  <condition>Pancreas Neoplasm</condition>
  <condition>Neuroendocrine Tumor Gastrointestinal, Hormone-Secreting</condition>
  <arm_group>
    <arm_group_label>EUS guided radiofrequency ablation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <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.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>EUS guided radiofrequency ablation</intervention_name>
    <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.</description>
    <arm_group_label>EUS guided radiofrequency ablation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        For all patients&#xD;
&#xD;
          -  Age ≥18 years and &lt;80 years&#xD;
&#xD;
          -  Signed written informed consent&#xD;
&#xD;
          -  Distance from the main pancreatic duct ≥2mm&#xD;
&#xD;
          -  Able to undergo endoscopic ultrasound examination&#xD;
&#xD;
          -  Homogeneous enhancement at contrast harmonic EUS (CH-EUS)&#xD;
&#xD;
        For patients with functional pancreatic neuroendocrine neoplasms (F-PanNENs), almost all&#xD;
        insulinomas&#xD;
&#xD;
          -  Definitive diagnosis of a clinical syndrome related to excessive insulin secretion&#xD;
             fasting test, insulin blood levels, C-peptide blood levels)&#xD;
&#xD;
          -  Single lesion visualized at CT, and/or MRI, and/or EUS&#xD;
&#xD;
          -  Size &lt; 20mm&#xD;
&#xD;
        For patients with non functional pancreatic neuroendocrine neoplasms (NF-PanNENs)&#xD;
&#xD;
          -  EUS fine needle biopsy (FNB) proven NF-PanNENs&#xD;
&#xD;
          -  68Ga-DOTATATE PET/CT positive for a pancreatic lesion and negative for lymph nodes,&#xD;
             liver, and other distant metastases&#xD;
&#xD;
          -  Hyper- or Iso-enhancing pattern at MRI and/or CT with negative lymph nodes, liver, and&#xD;
             other distant metastases&#xD;
&#xD;
          -  G1 or G2 ≤ 5% on histological examination of EUS-guided biopsy samples utilizing&#xD;
             EUS-FNB needles&#xD;
&#xD;
          -  Diameter between 15mm and 25mm,&#xD;
&#xD;
          -  Absence of symptoms&#xD;
&#xD;
          -  Absence of inner calcifications&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  For all patients&#xD;
&#xD;
          -  Known bleeding disorder that cannot be sufficiently corrected with co-fact or fresh&#xD;
             frozen plasma (FFP)&#xD;
&#xD;
          -  Use of anticoagulants that cannot be discontinued&#xD;
&#xD;
          -  INR &gt;1.5 or platelet count &lt;50.000&#xD;
&#xD;
          -  Previous inclusion in other studies&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Minimal distance from the main pancreatic duct &lt;1mm&#xD;
&#xD;
          -  Inability to sign the informed consent&#xD;
&#xD;
          -  Heterogeneous enhancement at contrast harmonic EUS (CH-EUS)&#xD;
&#xD;
        For patients with F-PanNENs (almost all insulinomas)&#xD;
&#xD;
          -  Diagnosis work up negative excessive hormone secretion syndrome&#xD;
&#xD;
          -  Multiple lesions visualized at CT, and/or MRI, and/or EUS&#xD;
&#xD;
          -  Size &gt; 20mm&#xD;
&#xD;
          -  For patients with NF-PanNENs&#xD;
&#xD;
          -  G2&gt;5% or G3 on histological examination of EUS-guided biopsy samples&#xD;
&#xD;
          -  Diameter &lt;15 mm and &gt;25 mm&#xD;
&#xD;
          -  Presence of symptoms&#xD;
&#xD;
          -  Presence of calcifications&#xD;
&#xD;
          -  Hypo-enhancing pattern at MRI and/or CT&#xD;
&#xD;
          -  68Ga-DOTATATE PET/CT positive for lymph nodes, liver, and other distant metastasis&#xD;
&#xD;
          -  Diagnosis on multiple endocrine neoplasia type 1 (MEN1) syndrome or Von Hippel Lindau&#xD;
             syndrome&#xD;
&#xD;
          -  Previous inclusion in other studies&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Alberto Larghi, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Fondazione Policlinico Universitario Agostino Gemelli</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Alberto Larghi, PhD</last_name>
    <phone>+390630156580</phone>
    <email>alberto.larghi@yahoo.it</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Carolina Gualtieri</last_name>
    <phone>+390630156580</phone>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Fondazione Policlinico Universitario Agostino Gemelli</name>
      <address>
        <city>Roma</city>
        <state>RM</state>
        <zip>00168</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Carolina Gualtieri</last_name>
      <phone>00390630156580</phone>
      <email>carolina.gualtieri@policlinicogemelli.it</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Universita' del Sacro Cuore</name>
      <address>
        <city>Rome</city>
        <zip>00136</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Alberto Larghi, MD</last_name>
      <phone>+390630156580</phone>
      <email>albertolarghi@yahoo.it</email>
    </contact>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>February 2022</verification_date>
  <study_first_submitted>February 4, 2019</study_first_submitted>
  <study_first_submitted_qc>February 6, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 8, 2019</study_first_posted>
  <last_update_submitted>February 10, 2022</last_update_submitted>
  <last_update_submitted_qc>February 10, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">February 11, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Catholic University of the Sacred Heart</investigator_affiliation>
    <investigator_full_name>Guido Costamagna</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms</mesh_term>
    <mesh_term>Neuroendocrine Tumors</mesh_term>
    <mesh_term>Carcinoma, Neuroendocrine</mesh_term>
    <mesh_term>Pancreatic Neoplasms</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03834701
org study id: RAPNEN
nct id: NCT03834701
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
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.
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.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence of adverse events (AEs) after EUS-guided radiofrequency ablation (RFA)
time frame: 1 year
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).
measure: Rates of secondary surgery
time frame: 1 year
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
arm group label: EUS guided radiofrequency ablation
arm group type: Experimental
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: EUS guided radiofrequency ablation
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.
arm group label: EUS guided radiofrequency ablation
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Alberto Larghi, PhD
role: Principal Investigator
affiliation: Fondazione Policlinico Universitario Agostino Gemelli
last name: Alberto Larghi, PhD
phone: +390630156580
email: alberto.larghi@yahoo.it
last name: Carolina Gualtieri
phone: +390630156580
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Recruiting
contact: 
country: Italy
responsible party type: Principal Investigator
investigator affiliation: Catholic University of the Sacred Heart
investigator full name: Guido Costamagna
investigator title: Professor
mesh term: Neoplasms
mesh term: Neuroendocrine Tumors
mesh term: Carcinoma, Neuroendocrine
mesh term: Pancreatic Neoplasms