<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/NCT03769753</url>
  </required_header>
  <id_info>
    <org_study_id>18-489</org_study_id>
    <nct_id>NCT03769753</nct_id>
  </id_info>
  <brief_title>Trial of IRE in Cholangiocarcinoma</brief_title>
  <official_title>Trial Of IRE in Cholangiocarcinoma (TOnIC): Phase II</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Memorial Sloan Kettering Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Memorial Sloan Kettering Cancer Center</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to test any good and bad side effects of surgery using IRE to&#xD;
      treat cancer of the bile duct.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 5, 2018</start_date>
  <completion_date type="Actual">August 16, 2021</completion_date>
  <primary_completion_date type="Actual">August 16, 2021</primary_completion_date>
  <phase>Phase 2</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>
    <intervention_model_description>This is a prospective, single-center phase I study.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Patients Experiencing a Clinically Relevant Complications</measure>
    <time_frame>within 30 days post-IRE</time_frame>
    <description>defined as CTCAE (version 5.0) grade 3 or higher complications</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">8</enrollment>
  <condition>Cholangiocarcinoma</condition>
  <arm_group>
    <arm_group_label>intraoperative use of IRE</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients with intraoperatively determined advanced unresectable PHC will be treated with IRE during the same surgical exploration session (N=20). Electrodes will be placed using ultrasound guidance. All electrodes will be placed by hepatopancreatobiliary surgeons with experience using IRE.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>IRE Device</intervention_name>
    <description>For use in ablating soft tissue</description>
    <arm_group_label>intraoperative use of IRE</arm_group_label>
    <other_name>The NanoKnife IRE device</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 18 years or older&#xD;
&#xD;
          -  Capable of providing written and oral informed consent in English&#xD;
&#xD;
          -  Locally advanced disease based on preoperative work-up demonstrating that the tumor is&#xD;
             unresectable due to portal vein, hepatic artery, and/or bile duct involvement,&#xD;
             insufficient hypertrophy response of the future liver remnant after portal vein&#xD;
             embolization, or patients not able to tolerate major liver surgery&#xD;
&#xD;
          -  Found to be unresectable intraoperatively based on vascular, biliary, or lymph node&#xD;
             (N2) involvement upon exploratory laparotomy&#xD;
&#xD;
          -  Patients will be assessed for chemotherapy prior to treatment with IRE, but given the&#xD;
             common problem of recurrent cholangitis, some patients will not be candidates for&#xD;
             chemotherapy until after IRE is performed.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Locally advanced PHC eligible and accepted for liver transplantation evaluation&#xD;
&#xD;
          -  PHC with &gt; 5 cm extension along the common hepatic duct or common bile duct on&#xD;
             preoperative imaging or intraoperative ultrasound&#xD;
&#xD;
          -  Metastases to peritoneum, liver or other organs confirmed by percutaneous biopsy,&#xD;
             staging laparoscopy or intraoperative frozen section&#xD;
&#xD;
          -  Lymph node metastases beyond N2 stations, confirmed by intraoperative frozen sections&#xD;
             or radiographic diagnosis&#xD;
&#xD;
          -  History of cardiac disease:&#xD;
&#xD;
               -  Congestive heart failure (NYHA class &gt;2)&#xD;
&#xD;
               -  Active Coronary Artery Disease (defined as myocardial infarction within 6 months&#xD;
                  prior to screening)&#xD;
&#xD;
               -  Cardiac arrhythmias requiring anti-arrhythmic therapy or pacemaker (beta blockers&#xD;
                  are permitted)&#xD;
&#xD;
          -  Any implanted stimulation device (defined as implantable cardiac device and a&#xD;
             pacemaker)&#xD;
&#xD;
          -  Uncontrolled hypertension (blood pressure must be ≤160/95 mmHg at the time of&#xD;
             screening on a stable antihypertensive regimen)&#xD;
&#xD;
          -  Uncontrolled infections (&gt; grade 2 NCI-CTC, version 3.0)&#xD;
&#xD;
          -  Epilepsy&#xD;
&#xD;
          -  Both narrowing (sclerosis) of the main portal vein and a reduced diameter of either&#xD;
             the common hepatic artery, celiac trunk or superior mesenteric artery of &gt;50%&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>T. Peter Kingham, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Memorial Sloan Kettering Cancer Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Memoral Sloan Kettering Basking Ridge (Consent and Follow up)</name>
      <address>
        <city>Basking Ridge</city>
        <state>New Jersey</state>
        <zip>07920</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memoral Sloan Kettering Monmouth (Consent and Follow up)</name>
      <address>
        <city>Middletown</city>
        <state>New Jersey</state>
        <zip>07748</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Bergen (Consent and Follow up)</name>
      <address>
        <city>Montvale</city>
        <state>New Jersey</state>
        <zip>07645</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Commack (Consent and Follow up)</name>
      <address>
        <city>Commack</city>
        <state>New York</state>
        <zip>11725</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memoral Sloan Kettering Westchester (Consent and Follow Up)</name>
      <address>
        <city>Harrison</city>
        <state>New York</state>
        <zip>10604</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Cancer Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Nassau (Consent and Follow-up)</name>
      <address>
        <city>Rockville Centre</city>
        <state>New York</state>
        <zip>11570</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.mskcc.org/mskcc/html/44.cfm</url>
    <description>Memorial Sloan Kettering Cancer Center</description>
  </link>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>December 6, 2018</study_first_submitted>
  <study_first_submitted_qc>December 6, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 7, 2018</study_first_posted>
  <results_first_submitted>August 16, 2022</results_first_submitted>
  <results_first_submitted_qc>August 16, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">September 10, 2022</results_first_posted>
  <last_update_submitted>August 16, 2022</last_update_submitted>
  <last_update_submitted_qc>August 16, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 10, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>intraoperative use of IRE</keyword>
  <keyword>18-489</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cholangiocarcinoma</mesh_term>
  </condition_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>November 4, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/53/NCT03769753/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Intraoperative Use of IRE</title>
          <description>Patients with intraoperatively determined advanced unresectable PHC will be treated with IRE during the same surgical exploration session (N=20). Electrodes will be placed using ultrasound guidance. All electrodes will be placed by hepatopancreatobiliary surgeons with experience using IRE.&#xD;
IRE Device: For use in ablating soft tissue</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Not Treated</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Inevaluable - No Evidence of Disease</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Intraoperative Use of IRE</title>
          <description>Patients with intraoperatively determined advanced unresectable PHC will be treated with IRE during the same surgical exploration session (N=20). Electrodes will be placed using ultrasound guidance. All electrodes will be placed by hepatopancreatobiliary surgeons with experience using IRE.&#xD;
IRE Device: For use in ablating soft tissue</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="8"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="72" lower_limit="64" upper_limit="78"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Patients Experiencing a Clinically Relevant Complications</title>
        <description>defined as CTCAE (version 5.0) grade 3 or higher complications</description>
        <time_frame>within 30 days post-IRE</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Intraoperative Use of IRE</title>
            <description>Patients with intraoperatively determined advanced unresectable PHC will be treated with IRE during the same surgical exploration session (N=20). Electrodes will be placed using ultrasound guidance. All electrodes will be placed by hepatopancreatobiliary surgeons with experience using IRE.&#xD;
IRE Device: For use in ablating soft tissue</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Patients Experiencing a Clinically Relevant Complications</title>
          <description>defined as CTCAE (version 5.0) grade 3 or higher complications</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Number of participants with grade 3 or higher complications</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Number of participants not evaluated for complications</title>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>within 30 days post-IRE</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Intraoperative Use of IRE</title>
          <description>Patients with intraoperatively determined advanced unresectable PHC will be treated with IRE during the same surgical exploration session (N=20). Electrodes will be placed using ultrasound guidance. All electrodes will be placed by hepatopancreatobiliary surgeons with experience using IRE.&#xD;
IRE Device: For use in ablating soft tissue</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alkaline phosphatase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>T. Peter Kingham, MD</name_or_title>
      <organization>Memorial Sloan Kettering Cancer Center</organization>
      <phone>212-639-5260</phone>
      <email>kinghamp@mskcc.org</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03769753
org study id: 18-489
nct id: NCT03769753
lead sponsor: 
is fda regulated drug: No
is fda regulated device: Yes
is us export: No
The purpose of this study is to test any good and bad side effects of surgery using IRE to
      treat cancer of the bile duct.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: This is a prospective, single-center phase I study.
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Patients Experiencing a Clinically Relevant Complications
time frame: within 30 days post-IRE
description: defined as CTCAE (version 5.0) grade 3 or higher complications
arm group label: intraoperative use of IRE
arm group type: Experimental
description: Patients with intraoperatively determined advanced unresectable PHC will be treated with IRE during the same surgical exploration session (N=20). Electrodes will be placed using ultrasound guidance. All electrodes will be placed by hepatopancreatobiliary surgeons with experience using IRE.
intervention type: Device
intervention name: IRE Device
description: For use in ablating soft tissue
arm group label: intraoperative use of IRE
other name: The NanoKnife IRE device
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: T. Peter Kingham, MD
role: Principal Investigator
affiliation: Memorial Sloan Kettering Cancer Center
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
url: http://www.mskcc.org/mskcc/html/44.cfm
description: Memorial Sloan Kettering Cancer Center
responsible party type: Sponsor
mesh term: Cholangiocarcinoma
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 