<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/NCT01692704</url>
  </required_header>
  <id_info>
    <org_study_id>ONK-USZ-003</org_study_id>
    <nct_id>NCT01692704</nct_id>
  </id_info>
  <brief_title>Downsizing of Unresectable Cholangiocarcinoma by Combined Intravenous and Intra-arterial Chemotherapy</brief_title>
  <official_title>Downstaging of Unresectable Intrahepatic or Hilar Cholangiocellular Carcinoma by Selective Intra-arterial Floxuridine and Systemic Cisplatin and Gemcitabine. A Dose Finding Single Center Phase IIa Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Zurich</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Zurich</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      An open label, prospective, non-randomized single arm study. Combination of two treatment&#xD;
      modalities - HAI with FUDR and systemic chemotherapy with cisplatin and gemcitabine.&#xD;
&#xD;
      Definition of the maximum tolerated dose (MTD) of intravenous gemcitabine in combination with&#xD;
      intravenous cisplatin and intra-arterial FUDR. Definition of safety and toxicity of this&#xD;
      combined regional and systemic treatment approach. Definition of the response rate after 3&#xD;
      months of hepatic intra-arterial chemotherapy with continuous infusion FUDR with or without&#xD;
      ligation of the right or left portal vein, in combination with 3 months of systemic cisplatin&#xD;
      and gemcitabine in patients with unresectable intrahepatic or hilar CCC.&#xD;
&#xD;
      A total of 9-18 patients are required. 3-6 patients per dose level. A maximum of three dose&#xD;
      levels (1 - 3) has been defined.&#xD;
&#xD;
      Statistical Methodology: Traditional 3+3 dosing algorithm to find MTD.&#xD;
&#xD;
        -  Trial with medicinal product&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>April 2012</start_date>
  <completion_date type="Actual">March 2016</completion_date>
  <primary_completion_date type="Actual">March 2016</primary_completion_date>
  <phase>Phase 1/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>Dose limiting toxicities (DLT) of intravenous gemcitabine with concomitant administration of FUDR-HAI and intravenous cisplatin.</measure>
    <time_frame>6 weeks</time_frame>
    <description>Dose limiting toxicities will be assessed to define the maximum tolerated dose (MTD) of gemcitabine in combination with fixed doses of cisplatin and FUDR. DLTs are per protocol prespecified AE or laboratory abnormalities observed during the first 6 weeks of study treatment. The MTD is one dose level below the dose level that caused DLTs in ≥ one third of patients (2 or more in a cohort of 6 patients), as determined by a traditional 3+3 algorithm.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Cholangiocellular Carcinoma</condition>
  <arm_group>
    <arm_group_label>HAI with FUDR &amp; systemic cisplatin and gemcitabin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>FUDR: 0.2mg/kg/day continuously i.a. for 14 days Cisplatin: 25mg/m2 i.v. Gemcitabin: different doses according to dose level 600, 800, or 1000 mg/m2 i.v.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Selective intra-arterial floxuridine and systemic gemcitabine and cisplatin</intervention_name>
    <description>Intra-arterial floxuridine:0.2 mg/KG/day for 14 days, repeated day 29. Overall 3 applications.&#xD;
Systemic cisplatin: 25 mg/m2 at days 1 and 8, repeated day 22. Overall 8 applications.&#xD;
Systemic gemcitabine: Three different dose levels will be tested; 600 mg/m2, 800 mg/m2, or 1000 mg/m2, at days 1 and 8, repeated day 22. Overall 8 applications.</description>
    <arm_group_label>HAI with FUDR &amp; systemic cisplatin and gemcitabin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          -  Histologically or cytologically proven cholangiocellular carcinoma including&#xD;
             gallbladder cancer.&#xD;
&#xD;
          -  Non-resectable cholangiocellular carcinoma as judged within an interdisciplinary&#xD;
             tumor-board including senior hepatobiliary surgeons. Non- resectability is based on&#xD;
             insufficient remnant liver volume.&#xD;
&#xD;
          -  Patient is not a candidate for liver transplantation&#xD;
&#xD;
          -  WHO Performance Score 0 or 1&#xD;
&#xD;
          -  No extrahepatic tumor, as evaluated by PET/CT scan of the chest and the abdomen/pelvis&#xD;
             with the exception of potentially resectable small lung nodules or hilar lymph node&#xD;
             involvement.&#xD;
&#xD;
          -  The assessment is done within 21 days before registration.&#xD;
&#xD;
          -  Adequate liver function or kidney function tests, including any of the following:&#xD;
&#xD;
               -  Bilirubin &lt; 2 x ULN&#xD;
&#xD;
               -  Aspartate-Aminotransferase (AST) &lt; 5 x ULN&#xD;
&#xD;
               -  Alanine-Aminotransferase (ALT) &lt; 5 x ULN&#xD;
&#xD;
               -  Alkaline phosphatase &lt; 5 x ULN&#xD;
&#xD;
               -  Estimated creatinine clearance &gt; 60 ml/min (using the Cockcroft formula)&#xD;
&#xD;
          -  Adequate hematological values:&#xD;
&#xD;
               -  Hemoglobin &gt; 80 G/L&#xD;
&#xD;
               -  Leucocytes &gt; 3.00 G/L,&#xD;
&#xD;
               -  Neutrophils &gt; 1.00 G/Ll&#xD;
&#xD;
               -  Platelets &gt; 100 G/L&#xD;
&#xD;
          -  Signed written informed consent&#xD;
&#xD;
          -  Patient age &gt;/= 18 years&#xD;
&#xD;
          -  Presentation of the case at the interdisciplinary tumor-board attended by&#xD;
             hepatobiliary surgeons, oncologists, hepatologists and radiologists&#xD;
&#xD;
          -  Women who are not breastfeeding and are using effective contraception if sexually&#xD;
             active, who are not pregnant and agree not to become pregnant during the 12 months&#xD;
             thereafter. A negative pregnancy test before inclusion into the trial is required for&#xD;
             women &lt; 50 years.&#xD;
&#xD;
          -  Men who agree not to father a child during participation in the trial or during the 12&#xD;
             months thereafter.&#xD;
&#xD;
          -  Patient compliance and geographic proximity allow proper staging and follow- up.&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  Anatomic variant in arteriogram which prevents selective delivery of the chemotherapy&#xD;
             to the liver&#xD;
&#xD;
          -  Life expectancy &lt; 3 months&#xD;
&#xD;
          -  Severe medical or psychiatric co-morbidity prohibiting the planned treatment or the&#xD;
             giving of informed consent&#xD;
&#xD;
          -  Any man or woman of childbearing age in case of inadequate contraception&#xD;
&#xD;
          -  Pregnancy or breastfeeding woman&#xD;
&#xD;
          -  Known hypersensitivity to trial drugs or hypersensitivity to any other component of&#xD;
             the trial drugs.&#xD;
&#xD;
          -  Treatment in clinical trial within 30 days prior to trial entry.&#xD;
&#xD;
          -  Active heart disease defined as congestive heart failure &gt; NYHA class 2&#xD;
&#xD;
          -  Past or current history (within the last 2 years prior to treatment start) of other&#xD;
             malignancies except basal and squamous cell carcinoma of the skin or in situ carcinoma&#xD;
             of the cervix&#xD;
&#xD;
          -  Inability or unwillingness to comply with the study protocol&#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>Panagiotis Samaras, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital Zurich, Department of Oncology</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Hospital Zurich, Department of Oncology</name>
      <address>
        <city>Zurich</city>
        <state>ZH</state>
        <zip>8091</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Switzerland</country>
  </location_countries>
  <verification_date>March 2016</verification_date>
  <study_first_submitted>June 6, 2012</study_first_submitted>
  <study_first_submitted_qc>September 20, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 25, 2012</study_first_posted>
  <last_update_submitted>March 24, 2016</last_update_submitted>
  <last_update_submitted_qc>March 24, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">March 25, 2016</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>Carcinoma</mesh_term>
    <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>Floxuridine</mesh_term>
  </intervention_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/NCT01692704
org study id: ONK-USZ-003
nct id: NCT01692704
lead sponsor: 
has dmc: Yes
An open label, prospective, non-randomized single arm study. Combination of two treatment
      modalities - HAI with FUDR and systemic chemotherapy with cisplatin and gemcitabine.

      Definition of the maximum tolerated dose (MTD) of intravenous gemcitabine in combination with
      intravenous cisplatin and intra-arterial FUDR. Definition of safety and toxicity of this
      combined regional and systemic treatment approach. Definition of the response rate after 3
      months of hepatic intra-arterial chemotherapy with continuous infusion FUDR with or without
      ligation of the right or left portal vein, in combination with 3 months of systemic cisplatin
      and gemcitabine in patients with unresectable intrahepatic or hilar CCC.

      A total of 9-18 patients are required. 3-6 patients per dose level. A maximum of three dose
      levels (1 - 3) has been defined.

      Statistical Methodology: Traditional 3+3 dosing algorithm to find MTD.

        -  Trial with medicinal product
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Dose limiting toxicities (DLT) of intravenous gemcitabine with concomitant administration of FUDR-HAI and intravenous cisplatin.
time frame: 6 weeks
description: Dose limiting toxicities will be assessed to define the maximum tolerated dose (MTD) of gemcitabine in combination with fixed doses of cisplatin and FUDR. DLTs are per protocol prespecified AE or laboratory abnormalities observed during the first 6 weeks of study treatment. The MTD is one dose level below the dose level that caused DLTs in ≥ one third of patients (2 or more in a cohort of 6 patients), as determined by a traditional 3+3 algorithm.
arm group label: HAI with FUDR & systemic cisplatin and gemcitabin
arm group type: Experimental
description: FUDR: 0.2mg/kg/day continuously i.a. for 14 days Cisplatin: 25mg/m2 i.v. Gemcitabin: different doses according to dose level 600, 800, or 1000 mg/m2 i.v.
intervention type: Drug
intervention name: Selective intra-arterial floxuridine and systemic gemcitabine and cisplatin
description: Intra-arterial floxuridine:0.2 mg/KG/day for 14 days, repeated day 29. Overall 3 applications.
Systemic cisplatin: 25 mg/m2 at days 1 and 8, repeated day 22. Overall 8 applications.
Systemic gemcitabine: Three different dose levels will be tested; 600 mg/m2, 800 mg/m2, or 1000 mg/m2, at days 1 and 8, repeated day 22. Overall 8 applications.
arm group label: HAI with FUDR & systemic cisplatin and gemcitabin
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Panagiotis Samaras, MD
role: Principal Investigator
affiliation: University Hospital Zurich, Department of Oncology
facility: 
country: Switzerland
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Cholangiocarcinoma
mesh term: Gemcitabine
mesh term: Floxuridine