<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/NCT02994251</url>
  </required_header>
  <id_info>
    <org_study_id>1603017367</org_study_id>
    <nct_id>NCT02994251</nct_id>
  </id_info>
  <brief_title>A Trial of Systemic Chemotherapy in Combination With Conventional Transarterial Chemoembolization in Patients With Advanced Intra-Hepatic Cholangiocarcinoma</brief_title>
  <official_title>A Phase II Trial of Systemic Chemotherapy (Gemcitabine and Cisplatin) in Combination With Conventional Transarterial Chemoembolization (cTACE) in Patients With Advanced Intra-Hepatic Cholangiocarcinoma (ICC)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Yale University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Yale University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The study will be a single-center, single-arm, Phase II study of gemcitabine and cisplatin in&#xD;
      combination with conventional trans-arterial chemoembolization therapy in adult patients with&#xD;
      advanced ICC. 25 patients will be enrolled over the course of 2 years, with an additional 1.5&#xD;
      years for patient follow-up.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Eligible patients enrolled on study will receive a chemotherapy regimen of gemcitabine and&#xD;
      cisplatin administered intravenously on Days 1 and 8 of a 21-day cycle. After every 2 cycles&#xD;
      of systemic chemotherapy, patients will receive contrast-enhanced MRI to assess liver&#xD;
      disease; conventional trans-arterial chemoembolization (TACE) will be performed as indicated&#xD;
      based on this assessment. Patients will receive a maximum of 8 cycles of the&#xD;
      gemcitabine/cisplatin combination. Up to 3 TACE treatments may be delivered in this same time&#xD;
      frame, with the first TACE taking place after 2 cycles of systemic chemotherapy. Following&#xD;
      the treatment period, patients will continue clinical follow-up at 3 month intervals until&#xD;
      study exit at 18 months post the start of treatment.&#xD;
&#xD;
      It is hypothesized that the addition of conventional transarterial chemoembolization to&#xD;
      standard chemotherapy will result in an improvement in PFS in patients with advanced,&#xD;
      unresectable ICC, including patients with extra-hepatic disease.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Study terminated due to low enrollment making it unlikely to meet recruitment goals.&#xD;
  </why_stopped>
  <start_date type="Actual">June 21, 2017</start_date>
  <completion_date type="Actual">November 6, 2018</completion_date>
  <primary_completion_date type="Actual">November 6, 2018</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Progression-free Survival</measure>
    <time_frame>12 months</time_frame>
    <description>The primary objective of this study is to evaluate the 12-month progression-free survival (PFS) rate in adult patients with intrahepatic cholangiocarcinoma (ICC) after treatment with gemcitabine and cisplatin in combination with conventional TACE. This is the percentage of patients alive and free of progression at 12-months from enrollment on study. Radiographic assessment of disease burden will be evaluated by mRECIST and qEASL using an MRI scan obtained at the IR clinic visit.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>18 months</time_frame>
    <description>Evaluation of overall survival (OS) of adult patients with advanced ICC treated with gemcitabine and cisplatin in combination with conventional TACE. Overall survival is the time from enrollment on study until death of the patient from any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Time to Progression (TTP)</measure>
    <time_frame>up to 18 months</time_frame>
    <description>Overall TTP is the time from enrollment on study until radiographic evidence of overall disease progression. Radiographic assessment will be evaluated by mRECIST using MRI every 2 cycles after intra-arterial therapy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Untreatable Progression (TTUP)</measure>
    <time_frame>up to 18 months</time_frame>
    <description>TTUP in liver lesions is measured from the time of initiation on cTACE therapy until radiographic evidence of disease progression in targeted lesions. Radiographic assessment will be evaluated by mRECIST using MRI every 2 cycles after intra-arterial therapy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Toxicities of the Gemcitabine and Cisplatin Regimen in Combination With cTACE Therapy Using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.</measure>
    <time_frame>18 months</time_frame>
    <description>To evaluate the toxicities of the gemcitabine and cisplatin regimen in combination with cTACE therapy in adult patients with advanced ICC. Safety will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation Between Changes in Dynamic Contrast-enhanced MRI of Liver Lesions and Progression Free Survival</measure>
    <time_frame>18 months</time_frame>
    <description>early changes in dynamic contrast-enhanced MRI (DCE-MRI) will correlate with long term PFS or OS, specifically as they relate to lesions targeted with cTACE therapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation Between Changes in Dynamic Contrast-enhanced MRI of Liver Lesions and Overall Survival</measure>
    <time_frame>18 months</time_frame>
    <description>early changes in dynamic contrast-enhanced MRI (DCE-MRI) will correlate with long term OS, specifically as they relate to lesions targeted with cTACE therapy</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">1</enrollment>
  <condition>Unresectable Intrahepatic Cholangiocarcinoma</condition>
  <arm_group>
    <arm_group_label>All subjects</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients must have advanced, unresectable intrahepatic cholangiocarcinoma (ICC) defined as biopsy-confirmed adenocarcinoma in the liver, with an immunohistochemical profile consistent with a pancreatico-biliary primary, not involving the common bile duct or bifurcation, and not amenable to surgical resection.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>gemcitabine</intervention_name>
    <description>1000 mg/m^2 of gemcitabine on Day 1 and 8, Dosages may be modified or delayed due to toxicities</description>
    <arm_group_label>All subjects</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cisplatin</intervention_name>
    <description>25 mg/m^2 on Day 1 and 8, Dosages may be modified or delayed due to toxicities</description>
    <arm_group_label>All subjects</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Conventional TACE (transarterial chemoembolization) with Doxorubicin/Mitomycin-C</intervention_name>
    <description>If conventional transarterial chemoembolization (TACE) is warranted based on MRI assessment and the patient meets all the eligibility criteria for TACE therapy, then cTACE will be scheduled to take place during Week 3 of that cycle. Patients will always receive the first cTACE for study; follow-up cTACE will occur on demand.</description>
    <arm_group_label>All subjects</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patient is at least 18 years of age.&#xD;
&#xD;
          -  Patient has advanced, unresectable intrahepatic cholangiocarcinoma (ICC). Advanced,&#xD;
             unresectable ICC is defined as biopsy-confirmed adenocarcinoma in the liver, with an&#xD;
             immunohistochemical profile consistent with a pancreatico-biliary primary, not&#xD;
             involving the common bile duct or bifurcation, and not amenable to surgical resection.&#xD;
&#xD;
          -  Eligible for conventional TACE as defined by local treatment guidelines.&#xD;
&#xD;
          -  Child-Pugh class of A to B7.&#xD;
&#xD;
          -  Adequate end-organ and bone marrow function as manifested as:&#xD;
&#xD;
               -  Hemoglobin ≥ 9 g/dL&#xD;
&#xD;
               -  Absolute neutrophil count ≥ 1500/mm3&#xD;
&#xD;
               -  Creatinine ≤ 2.0 g/dL&#xD;
&#xD;
               -  AST and ALT ≤ 5 x ULN&#xD;
&#xD;
               -  Albumin ≥ 2.4 mg/dL&#xD;
&#xD;
               -  Total bilirubin ≤ 2.5 mg/dL&#xD;
&#xD;
               -  Platelets ≥ 100,000/mm3&#xD;
&#xD;
               -  For TACE procedures, subjects are allowed to have platelets ≥ 75,000/mm3.&#xD;
&#xD;
          -  Disease is liver-dominant with &gt;70% of measurable disease burden within the hepatic&#xD;
             parenchyma.&#xD;
&#xD;
          -  No prior surgery or chemotherapy for ICC.&#xD;
&#xD;
          -  ECOG performance status of 0-1.&#xD;
&#xD;
          -  No other active malignancy within 2 years.&#xD;
&#xD;
          -  Women of child-bearing potential and men must agree to use adequate contraception&#xD;
             prior to study entry and for the duration of the study.&#xD;
&#xD;
          -  Ability to understand and willingness to sign a written informed consent document.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior or concurrent chemotherapy treatment for advanced ICC.&#xD;
&#xD;
          -  History of allergic reactions attributed to compounds of similar chemical or&#xD;
             biological composition to gemcitabine, cisplatin, doxorubicin, or mitomycin-C.&#xD;
&#xD;
          -  Active treatment with CYP3A4 strong inhibitors or inducers.&#xD;
&#xD;
          -  Recent surgical procedure within 21 days of study enrollment.&#xD;
&#xD;
          -  Severe and/or uncontrolled co-morbid medical conditions including, but not limited to,&#xD;
             active infection, viral hepatitis, congestive heart failure, cardiac arrhythmia,&#xD;
             unstable angina pectoris, and psychiatric illness or social circumstance that would&#xD;
             limit compliance with study requirements.&#xD;
&#xD;
          -  Pregnancy during study duration.&#xD;
&#xD;
          -  Active immunosuppressive medications.&#xD;
&#xD;
          -  Presence of grade 2 or higher hepatic encephalopathy.&#xD;
&#xD;
          -  Complete occlusion of the entire portal venous system. Partial or branch portal vein&#xD;
             occlusion allowed if without reversal of flow.&#xD;
&#xD;
          -  Radiotherapy within 21 days from treatment with study interventions or medications.&#xD;
&#xD;
          -  Current, recent (within 4 weeks of first infusion of this study), or planned&#xD;
             participation in additional experimental drug.&#xD;
&#xD;
          -  Unstable angina.&#xD;
&#xD;
          -  New York Heart Association (NYHA) Grade II or greater congestive heart failure&#xD;
             (Appendix C).&#xD;
&#xD;
          -  History of myocardial infarction or CVA within 6 months prior to study enrollment.&#xD;
&#xD;
          -  Clinically significant peripheral vascular disease.&#xD;
&#xD;
          -  Inability to comply with study and/or follow-up procedures.&#xD;
&#xD;
          -  Life expectancy of less than 12 weeks.&#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>Todd Schlachter</last_name>
    <role>Principal Investigator</role>
    <affiliation>Yale University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Smilow Cancer Center</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06510</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2019</verification_date>
  <study_first_submitted>December 6, 2016</study_first_submitted>
  <study_first_submitted_qc>December 14, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 15, 2016</study_first_posted>
  <results_first_submitted>December 6, 2019</results_first_submitted>
  <results_first_submitted_qc>December 6, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">December 30, 2019</results_first_posted>
  <last_update_submitted>December 6, 2019</last_update_submitted>
  <last_update_submitted_qc>December 6, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">December 30, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cholangiocarcinoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Gemcitabine</mesh_term>
    <mesh_term>Doxorubicin</mesh_term>
    <mesh_term>Mitomycins</mesh_term>
    <mesh_term>Mitomycin</mesh_term>
  </intervention_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>July 19, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/51/NCT02994251/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>All Subjects</title>
          <description>Patients must have advanced, unresectable intrahepatic cholangiocarcinoma (ICC) defined as biopsy-confirmed adenocarcinoma in the liver, with an immunohistochemical profile consistent with a pancreatico-biliary primary, not involving the common bile duct or bifurcation, and not amenable to surgical resection.&#xD;
gemcitabine: 1000 mg/m^2 of gemcitabine on Day 1 and 8, Dosages may be modified or delayed due to toxicities&#xD;
Cisplatin: 25 mg/m^2 on Day 1 and 8, Dosages may be modified or delayed due to toxicities&#xD;
Conventional TACE (transarterial chemoembolization) with Doxorubicin/Mitomycin-C: If conventional transarterial chemoembolization (TACE) is warranted based on MRI assessment and the patient meets all the eligibility criteria for TACE therapy, then cTACE will be scheduled to take place during Week 3 of that cycle. Patients will always receive the first cTACE for study; follow-up cTACE will occur on demand.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Confidentiality is a concern as the study was terminated after 1 patient was enrolled, thus any reported data would indicate PHI for this subject.</population>
      <group_list>
        <group group_id="B1">
          <title>All Subjects</title>
          <description>Patients must have advanced, unresectable intrahepatic cholangiocarcinoma (ICC) defined as biopsy-confirmed adenocarcinoma in the liver, with an immunohistochemical profile consistent with a pancreatico-biliary primary, not involving the common bile duct or bifurcation, and not amenable to surgical resection.&#xD;
gemcitabine: 1000 mg/m^2 of gemcitabine on Day 1 and 8, Dosages may be modified or delayed due to toxicities&#xD;
Cisplatin: 25 mg/m^2 on Day 1 and 8, Dosages may be modified or delayed due to toxicities&#xD;
Conventional TACE (transarterial chemoembolization) with Doxorubicin/Mitomycin-C: If conventional transarterial chemoembolization (TACE) is warranted based on MRI assessment and the patient meets all the eligibility criteria for TACE therapy, then cTACE will be scheduled to take place during Week 3 of that cycle. Patients will always receive the first cTACE for study; follow-up cTACE will occur on demand.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="0"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                </category>
                <category>
                  <title>Male</title>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                </category>
                <category>
                  <title>Asian</title>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                </category>
                <category>
                  <title>Black or African American</title>
                </category>
                <category>
                  <title>White</title>
                </category>
                <category>
                  <title>More than one race</title>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <class_list>
            <class>
              <title>United States</title>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Progression-free Survival</title>
        <description>The primary objective of this study is to evaluate the 12-month progression-free survival (PFS) rate in adult patients with intrahepatic cholangiocarcinoma (ICC) after treatment with gemcitabine and cisplatin in combination with conventional TACE. This is the percentage of patients alive and free of progression at 12-months from enrollment on study. Radiographic assessment of disease burden will be evaluated by mRECIST and qEASL using an MRI scan obtained at the IR clinic visit.</description>
        <time_frame>12 months</time_frame>
        <population>Confidentiality is a concern as the study was terminated after 1 patient was enrolled, thus any reported data would indicate PHI for this subject. To prevent this, it was advised to enter 0 as the number of participants analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>All Subjects</title>
            <description>Patients must have advanced, unresectable intrahepatic cholangiocarcinoma (ICC) defined as biopsy-confirmed adenocarcinoma in the liver, with an immunohistochemical profile consistent with a pancreatico-biliary primary, not involving the common bile duct or bifurcation, and not amenable to surgical resection.&#xD;
gemcitabine: 1000 mg/m^2 of gemcitabine on Day 1 and 8, Dosages may be modified or delayed due to toxicities&#xD;
Cisplatin: 25 mg/m^2 on Day 1 and 8, Dosages may be modified or delayed due to toxicities&#xD;
Conventional TACE (transarterial chemoembolization) with Doxorubicin/Mitomycin-C: If conventional transarterial chemoembolization (TACE) is warranted based on MRI assessment and the patient meets all the eligibility criteria for TACE therapy, then cTACE will be scheduled to take place during Week 3 of that cycle. Patients will always receive the first cTACE for study; follow-up cTACE will occur on demand.</description>
          </group>
        </group_list>
        <measure>
          <title>Progression-free Survival</title>
          <description>The primary objective of this study is to evaluate the 12-month progression-free survival (PFS) rate in adult patients with intrahepatic cholangiocarcinoma (ICC) after treatment with gemcitabine and cisplatin in combination with conventional TACE. This is the percentage of patients alive and free of progression at 12-months from enrollment on study. Radiographic assessment of disease burden will be evaluated by mRECIST and qEASL using an MRI scan obtained at the IR clinic visit.</description>
          <population>Confidentiality is a concern as the study was terminated after 1 patient was enrolled, thus any reported data would indicate PHI for this subject. To prevent this, it was advised to enter 0 as the number of participants analyzed.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival</title>
        <description>Evaluation of overall survival (OS) of adult patients with advanced ICC treated with gemcitabine and cisplatin in combination with conventional TACE. Overall survival is the time from enrollment on study until death of the patient from any cause.</description>
        <time_frame>18 months</time_frame>
        <population>Confidentiality is a concern as the study was terminated after 1 patient was enrolled, thus any reported data would indicate PHI for this subject. To prevent this, it was advised to enter 0 as the number of participants analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>All Subjects</title>
            <description>Patients must have advanced, unresectable intrahepatic cholangiocarcinoma (ICC) defined as biopsy-confirmed adenocarcinoma in the liver, with an immunohistochemical profile consistent with a pancreatico-biliary primary, not involving the common bile duct or bifurcation, and not amenable to surgical resection.&#xD;
gemcitabine: 1000 mg/m^2 of gemcitabine on Day 1 and 8, Dosages may be modified or delayed due to toxicities&#xD;
Cisplatin: 25 mg/m^2 on Day 1 and 8, Dosages may be modified or delayed due to toxicities&#xD;
Conventional TACE (transarterial chemoembolization) with Doxorubicin/Mitomycin-C: If conventional transarterial chemoembolization (TACE) is warranted based on MRI assessment and the patient meets all the eligibility criteria for TACE therapy, then cTACE will be scheduled to take place during Week 3 of that cycle. Patients will always receive the first cTACE for study; follow-up cTACE will occur on demand.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival</title>
          <description>Evaluation of overall survival (OS) of adult patients with advanced ICC treated with gemcitabine and cisplatin in combination with conventional TACE. Overall survival is the time from enrollment on study until death of the patient from any cause.</description>
          <population>Confidentiality is a concern as the study was terminated after 1 patient was enrolled, thus any reported data would indicate PHI for this subject. To prevent this, it was advised to enter 0 as the number of participants analyzed.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Time to Progression (TTP)</title>
        <description>Overall TTP is the time from enrollment on study until radiographic evidence of overall disease progression. Radiographic assessment will be evaluated by mRECIST using MRI every 2 cycles after intra-arterial therapy.</description>
        <time_frame>up to 18 months</time_frame>
        <population>Confidentiality is a concern as the study was terminated after 1 patient was enrolled, thus any reported data would indicate PHI for this subject. To prevent this, it was advised to enter 0 as the number of participants analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>All Subjects</title>
            <description>Patients must have advanced, unresectable intrahepatic cholangiocarcinoma (ICC) defined as biopsy-confirmed adenocarcinoma in the liver, with an immunohistochemical profile consistent with a pancreatico-biliary primary, not involving the common bile duct or bifurcation, and not amenable to surgical resection.&#xD;
gemcitabine: 1000 mg/m^2 of gemcitabine on Day 1 and 8, Dosages may be modified or delayed due to toxicities&#xD;
Cisplatin: 25 mg/m^2 on Day 1 and 8, Dosages may be modified or delayed due to toxicities&#xD;
Conventional TACE (transarterial chemoembolization) with Doxorubicin/Mitomycin-C: If conventional transarterial chemoembolization (TACE) is warranted based on MRI assessment and the patient meets all the eligibility criteria for TACE therapy, then cTACE will be scheduled to take place during Week 3 of that cycle. Patients will always receive the first cTACE for study; follow-up cTACE will occur on demand.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Time to Progression (TTP)</title>
          <description>Overall TTP is the time from enrollment on study until radiographic evidence of overall disease progression. Radiographic assessment will be evaluated by mRECIST using MRI every 2 cycles after intra-arterial therapy.</description>
          <population>Confidentiality is a concern as the study was terminated after 1 patient was enrolled, thus any reported data would indicate PHI for this subject. To prevent this, it was advised to enter 0 as the number of participants analyzed.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Untreatable Progression (TTUP)</title>
        <description>TTUP in liver lesions is measured from the time of initiation on cTACE therapy until radiographic evidence of disease progression in targeted lesions. Radiographic assessment will be evaluated by mRECIST using MRI every 2 cycles after intra-arterial therapy.</description>
        <time_frame>up to 18 months</time_frame>
        <population>Confidentiality is a concern as the study was terminated after 1 patient was enrolled, thus any reported data would indicate PHI for this subject. To prevent this, it was advised to enter 0 as the number of participants analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>All Subjects</title>
            <description>Patients must have advanced, unresectable intrahepatic cholangiocarcinoma (ICC) defined as biopsy-confirmed adenocarcinoma in the liver, with an immunohistochemical profile consistent with a pancreatico-biliary primary, not involving the common bile duct or bifurcation, and not amenable to surgical resection.&#xD;
gemcitabine: 1000 mg/m^2 of gemcitabine on Day 1 and 8, Dosages may be modified or delayed due to toxicities&#xD;
Cisplatin: 25 mg/m^2 on Day 1 and 8, Dosages may be modified or delayed due to toxicities&#xD;
Conventional TACE (transarterial chemoembolization) with Doxorubicin/Mitomycin-C: If conventional transarterial chemoembolization (TACE) is warranted based on MRI assessment and the patient meets all the eligibility criteria for TACE therapy, then cTACE will be scheduled to take place during Week 3 of that cycle. Patients will always receive the first cTACE for study; follow-up cTACE will occur on demand.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Untreatable Progression (TTUP)</title>
          <description>TTUP in liver lesions is measured from the time of initiation on cTACE therapy until radiographic evidence of disease progression in targeted lesions. Radiographic assessment will be evaluated by mRECIST using MRI every 2 cycles after intra-arterial therapy.</description>
          <population>Confidentiality is a concern as the study was terminated after 1 patient was enrolled, thus any reported data would indicate PHI for this subject. To prevent this, it was advised to enter 0 as the number of participants analyzed.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Toxicities of the Gemcitabine and Cisplatin Regimen in Combination With cTACE Therapy Using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.</title>
        <description>To evaluate the toxicities of the gemcitabine and cisplatin regimen in combination with cTACE therapy in adult patients with advanced ICC. Safety will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.</description>
        <time_frame>18 months</time_frame>
        <population>Confidentiality is a concern as the study was terminated after 1 patient was enrolled, thus any reported data would indicate PHI for this subject. To prevent this, it was advised to enter 0 as the number of participants analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>All Subjects</title>
            <description>Patients must have advanced, unresectable intrahepatic cholangiocarcinoma (ICC) defined as biopsy-confirmed adenocarcinoma in the liver, with an immunohistochemical profile consistent with a pancreatico-biliary primary, not involving the common bile duct or bifurcation, and not amenable to surgical resection.&#xD;
gemcitabine: 1000 mg/m^2 of gemcitabine on Day 1 and 8, Dosages may be modified or delayed due to toxicities&#xD;
Cisplatin: 25 mg/m^2 on Day 1 and 8, Dosages may be modified or delayed due to toxicities&#xD;
Conventional TACE (transarterial chemoembolization) with Doxorubicin/Mitomycin-C: If conventional transarterial chemoembolization (TACE) is warranted based on MRI assessment and the patient meets all the eligibility criteria for TACE therapy, then cTACE will be scheduled to take place during Week 3 of that cycle. Patients will always receive the first cTACE for study; follow-up cTACE will occur on demand.</description>
          </group>
        </group_list>
        <measure>
          <title>Toxicities of the Gemcitabine and Cisplatin Regimen in Combination With cTACE Therapy Using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.</title>
          <description>To evaluate the toxicities of the gemcitabine and cisplatin regimen in combination with cTACE therapy in adult patients with advanced ICC. Safety will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.</description>
          <population>Confidentiality is a concern as the study was terminated after 1 patient was enrolled, thus any reported data would indicate PHI for this subject. To prevent this, it was advised to enter 0 as the number of participants analyzed.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Correlation Between Changes in Dynamic Contrast-enhanced MRI of Liver Lesions and Progression Free Survival</title>
        <description>early changes in dynamic contrast-enhanced MRI (DCE-MRI) will correlate with long term PFS or OS, specifically as they relate to lesions targeted with cTACE therapy</description>
        <time_frame>18 months</time_frame>
        <population>Confidentiality is a concern as the study was terminated after 1 patient was enrolled, thus any reported data would indicate PHI for this subject. To prevent this, it was advised to enter 0 as the number of participants analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>All Subjects</title>
            <description>Patients must have advanced, unresectable intrahepatic cholangiocarcinoma (ICC) defined as biopsy-confirmed adenocarcinoma in the liver, with an immunohistochemical profile consistent with a pancreatico-biliary primary, not involving the common bile duct or bifurcation, and not amenable to surgical resection.&#xD;
gemcitabine: 1000 mg/m^2 of gemcitabine on Day 1 and 8, Dosages may be modified or delayed due to toxicities&#xD;
Cisplatin: 25 mg/m^2 on Day 1 and 8, Dosages may be modified or delayed due to toxicities&#xD;
Conventional TACE (transarterial chemoembolization) with Doxorubicin/Mitomycin-C: If conventional transarterial chemoembolization (TACE) is warranted based on MRI assessment and the patient meets all the eligibility criteria for TACE therapy, then cTACE will be scheduled to take place during Week 3 of that cycle. Patients will always receive the first cTACE for study; follow-up cTACE will occur on demand.</description>
          </group>
        </group_list>
        <measure>
          <title>Correlation Between Changes in Dynamic Contrast-enhanced MRI of Liver Lesions and Progression Free Survival</title>
          <description>early changes in dynamic contrast-enhanced MRI (DCE-MRI) will correlate with long term PFS or OS, specifically as they relate to lesions targeted with cTACE therapy</description>
          <population>Confidentiality is a concern as the study was terminated after 1 patient was enrolled, thus any reported data would indicate PHI for this subject. To prevent this, it was advised to enter 0 as the number of participants analyzed.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Correlation Between Changes in Dynamic Contrast-enhanced MRI of Liver Lesions and Overall Survival</title>
        <description>early changes in dynamic contrast-enhanced MRI (DCE-MRI) will correlate with long term OS, specifically as they relate to lesions targeted with cTACE therapy</description>
        <time_frame>18 months</time_frame>
        <population>Confidentiality is a concern as the study was terminated after 1 patient was enrolled, thus any reported data would indicate PHI for this subject. To prevent this, it was advised to enter 0 as the number of participants analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>All Subjects</title>
            <description>Patients must have advanced, unresectable intrahepatic cholangiocarcinoma (ICC) defined as biopsy-confirmed adenocarcinoma in the liver, with an immunohistochemical profile consistent with a pancreatico-biliary primary, not involving the common bile duct or bifurcation, and not amenable to surgical resection.&#xD;
gemcitabine: 1000 mg/m^2 of gemcitabine on Day 1 and 8, Dosages may be modified or delayed due to toxicities&#xD;
Cisplatin: 25 mg/m^2 on Day 1 and 8, Dosages may be modified or delayed due to toxicities&#xD;
Conventional TACE (transarterial chemoembolization) with Doxorubicin/Mitomycin-C: If conventional transarterial chemoembolization (TACE) is warranted based on MRI assessment and the patient meets all the eligibility criteria for TACE therapy, then cTACE will be scheduled to take place during Week 3 of that cycle. Patients will always receive the first cTACE for study; follow-up cTACE will occur on demand.</description>
          </group>
        </group_list>
        <measure>
          <title>Correlation Between Changes in Dynamic Contrast-enhanced MRI of Liver Lesions and Overall Survival</title>
          <description>early changes in dynamic contrast-enhanced MRI (DCE-MRI) will correlate with long term OS, specifically as they relate to lesions targeted with cTACE therapy</description>
          <population>Confidentiality is a concern as the study was terminated after 1 patient was enrolled, thus any reported data would indicate PHI for this subject. To prevent this, it was advised to enter 0 as the number of participants analyzed.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events collected at baseline until patient exit at 18 months post start of therapy.</time_frame>
      <desc>Confidentiality is a concern as the study was terminated after 1 patient was enrolled, thus any reported data would indicate PHI for this subject. To prevent this, it was advised to enter 0 as the number of participants analyzed.</desc>
      <group_list>
        <group group_id="E1">
          <title>All Subjects</title>
          <description>Patients must have advanced, unresectable intrahepatic cholangiocarcinoma (ICC) defined as biopsy-confirmed adenocarcinoma in the liver, with an immunohistochemical profile consistent with a pancreatico-biliary primary, not involving the common bile duct or bifurcation, and not amenable to surgical resection.&#xD;
gemcitabine: 1000 mg/m^2 of gemcitabine on Day 1 and 8, Dosages may be modified or delayed due to toxicities&#xD;
Cisplatin: 25 mg/m^2 on Day 1 and 8, Dosages may be modified or delayed due to toxicities&#xD;
Conventional TACE (transarterial chemoembolization) with Doxorubicin/Mitomycin-C: If conventional transarterial chemoembolization (TACE) is warranted based on MRI assessment and the patient meets all the eligibility criteria for TACE therapy, then cTACE will be scheduled to take place during Week 3 of that cycle. Patients will always receive the first cTACE for study; follow-up cTACE will occur on demand.</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="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="0"/>
              </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>
    <limitations_and_caveats>Trial was terminated early due to low enrollment, leading to endpoints not being achievable.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Dr. Todd Schlachter</name_or_title>
      <organization>Yale University</organization>
      <phone>203-785-5885</phone>
      <email>todd.schlachter@yale.edu</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/NCT02994251
org study id: 1603017367
nct id: NCT02994251
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
The study will be a single-center, single-arm, Phase II study of gemcitabine and cisplatin in
      combination with conventional trans-arterial chemoembolization therapy in adult patients with
      advanced ICC. 25 patients will be enrolled over the course of 2 years, with an additional 1.5
      years for patient follow-up.
Eligible patients enrolled on study will receive a chemotherapy regimen of gemcitabine and
      cisplatin administered intravenously on Days 1 and 8 of a 21-day cycle. After every 2 cycles
      of systemic chemotherapy, patients will receive contrast-enhanced MRI to assess liver
      disease; conventional trans-arterial chemoembolization (TACE) will be performed as indicated
      based on this assessment. Patients will receive a maximum of 8 cycles of the
      gemcitabine/cisplatin combination. Up to 3 TACE treatments may be delivered in this same time
      frame, with the first TACE taking place after 2 cycles of systemic chemotherapy. Following
      the treatment period, patients will continue clinical follow-up at 3 month intervals until
      study exit at 18 months post the start of treatment.

      It is hypothesized that the addition of conventional transarterial chemoembolization to
      standard chemotherapy will result in an improvement in PFS in patients with advanced,
      unresectable ICC, including patients with extra-hepatic disease.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Progression-free Survival
time frame: 12 months
description: The primary objective of this study is to evaluate the 12-month progression-free survival (PFS) rate in adult patients with intrahepatic cholangiocarcinoma (ICC) after treatment with gemcitabine and cisplatin in combination with conventional TACE. This is the percentage of patients alive and free of progression at 12-months from enrollment on study. Radiographic assessment of disease burden will be evaluated by mRECIST and qEASL using an MRI scan obtained at the IR clinic visit.
measure: Overall Survival
time frame: 18 months
description: Evaluation of overall survival (OS) of adult patients with advanced ICC treated with gemcitabine and cisplatin in combination with conventional TACE. Overall survival is the time from enrollment on study until death of the patient from any cause.
measure: Overall Time to Progression (TTP)
time frame: up to 18 months
description: Overall TTP is the time from enrollment on study until radiographic evidence of overall disease progression. Radiographic assessment will be evaluated by mRECIST using MRI every 2 cycles after intra-arterial therapy.
measure: Time to Untreatable Progression (TTUP)
time frame: up to 18 months
description: TTUP in liver lesions is measured from the time of initiation on cTACE therapy until radiographic evidence of disease progression in targeted lesions. Radiographic assessment will be evaluated by mRECIST using MRI every 2 cycles after intra-arterial therapy.
measure: Toxicities of the Gemcitabine and Cisplatin Regimen in Combination With cTACE Therapy Using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.
time frame: 18 months
description: To evaluate the toxicities of the gemcitabine and cisplatin regimen in combination with cTACE therapy in adult patients with advanced ICC. Safety will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
measure: Correlation Between Changes in Dynamic Contrast-enhanced MRI of Liver Lesions and Progression Free Survival
time frame: 18 months
description: early changes in dynamic contrast-enhanced MRI (DCE-MRI) will correlate with long term PFS or OS, specifically as they relate to lesions targeted with cTACE therapy
measure: Correlation Between Changes in Dynamic Contrast-enhanced MRI of Liver Lesions and Overall Survival
time frame: 18 months
description: early changes in dynamic contrast-enhanced MRI (DCE-MRI) will correlate with long term OS, specifically as they relate to lesions targeted with cTACE therapy
arm group label: All subjects
arm group type: Experimental
description: Patients must have advanced, unresectable intrahepatic cholangiocarcinoma (ICC) defined as biopsy-confirmed adenocarcinoma in the liver, with an immunohistochemical profile consistent with a pancreatico-biliary primary, not involving the common bile duct or bifurcation, and not amenable to surgical resection.
intervention type: Drug
intervention name: gemcitabine
description: 1000 mg/m^2 of gemcitabine on Day 1 and 8, Dosages may be modified or delayed due to toxicities
arm group label: All subjects
intervention type: Drug
intervention name: Cisplatin
description: 25 mg/m^2 on Day 1 and 8, Dosages may be modified or delayed due to toxicities
arm group label: All subjects
intervention type: Drug
intervention name: Conventional TACE (transarterial chemoembolization) with Doxorubicin/Mitomycin-C
description: If conventional transarterial chemoembolization (TACE) is warranted based on MRI assessment and the patient meets all the eligibility criteria for TACE therapy, then cTACE will be scheduled to take place during Week 3 of that cycle. Patients will always receive the first cTACE for study; follow-up cTACE will occur on demand.
arm group label: All subjects
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Todd Schlachter
role: Principal Investigator
affiliation: Yale University
facility: 
country: United States
responsible party type: Sponsor
mesh term: Cholangiocarcinoma
mesh term: Gemcitabine
mesh term: Doxorubicin
mesh term: Mitomycins
mesh term: Mitomycin
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Trial was terminated early due to low enrollment, leading to endpoints not being achievable.
point of contact: 