<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/NCT03259867</url>
  </required_header>
  <id_info>
    <org_study_id>LT-004</org_study_id>
    <nct_id>NCT03259867</nct_id>
  </id_info>
  <brief_title>Combination of TATE and PD-1 Inhibitor in Liver Cancer</brief_title>
  <acronym>TATE-PD1</acronym>
  <official_title>Phase IIA Single-Arm Study of Treatment of Patients With Advanced Liver Cancer With a Combination of TATE (Transarterial Tirapazamine Embolization) Followed by an Anti-PD-1 Monoclonal Antibody</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Teclison Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Teclison Ltd.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a multi-center, open-label phase IIA study that investigates the preliminary efficacy&#xD;
      of Trans-arterial Tirapazamine Embolization (TATE) treatment of liver cancer followed by a&#xD;
      PD-1 checkpoint inhibitor (nivolumab). Patients with two types of cancers will be enrolled,&#xD;
      advanced hepatocellular carcinoma (HCC),and metastatic gastric cancer. All enrolled patients&#xD;
      need to have liver lesions and have progressed on a prior immune checkpoint inhibitor.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The goal of the study is to investigate whether tumor necrosis induced by Trans-arterial&#xD;
      Tirapazamine Embolization (TATE) treatment can boost anti-tumor immunity and enhance the&#xD;
      therapeutic efficacy of immune checkpoint inhibitor. Patients with advanced liver cancers&#xD;
      (primary HCC or metastatic gastric cancer) who have progressed on a prior immune checkpoint&#xD;
      inhibitor will be enrolled in the study. Liver lesions will be treated with up to 4 TATE&#xD;
      treatments for optimal debulking, which also serve as a vaccination process toward tumor.&#xD;
      Lesion not treated with TATE will be used for monitoring the response toward a PD-1 inhibitor&#xD;
      (Nivolumab) for abscopal effect. If a patient subsequently develops an &quot;escape&quot; to the PD-1&#xD;
      inhibitor, patient can have another 2 TATE treatments of the escaped tumor lesion. Dosing of&#xD;
      the PD-1 inhibitor is per standard FDA-approved dosing schedule and continues until&#xD;
      progressive disease. The efficacy will be assessed by the response rate (RR) using RECIST.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">July 1, 2017</start_date>
  <completion_date type="Anticipated">December 31, 2024</completion_date>
  <primary_completion_date type="Anticipated">May 31, 2024</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>One arm for advanced HCC, and one for second line metastatic gastro-esophageal cancer . All enrolled patients will receive the same treatment with TATE and a PD-1 inhibitor (nivolumab) until disease progression</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Overall Response Rate</measure>
    <time_frame>up to 24 months</time_frame>
    <description>Per RECIST 1.1 criteria</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Duration of Response</measure>
    <time_frame>up to 24 months</time_frame>
    <description>From the date of image-demonstrated response to the date of progression</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Progression</measure>
    <time_frame>up to 24 months</time_frame>
    <description>From randomization to disease progression or death</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival</measure>
    <time_frame>up to 24 months</time_frame>
    <description>From randomization to disease progression or death</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>through study completion, an average of 3 years</time_frame>
    <description>From randomization to death</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">54</enrollment>
  <condition>Hepatocellular Carcinoma</condition>
  <condition>Gastric Cancer</condition>
  <arm_group>
    <arm_group_label>Advanced Hepatocellular carcinoma</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>PD-1 inhibitor (Nivolumab 480 mg Q4W IV ) starts at day 1, and continues until progression.&#xD;
TATE treatment starts at day 8 for debulking up to 4 cycles. If escape lesion appears, two more TATE treatments can be given. Tirapazamine dose at 35 mg flat dose given before embolization.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Metastatic Gastro-esophageal cancer</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>PD-1 inhibitor (Nivolumab 480 mg Q4W IV) starts at day 1, and continues until progression.&#xD;
TATE treatment starts at day 8 for debulking up to 4 cycles. If escape lesion appears, two more TATE treatments can be given. Tirapazamine dose at 35 mg flat dose given before embolization.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nivolumab Injectable Product</intervention_name>
    <description>a PD-1 immune check inhibitor</description>
    <arm_group_label>Advanced Hepatocellular carcinoma</arm_group_label>
    <arm_group_label>Metastatic Gastro-esophageal cancer</arm_group_label>
    <other_name>OPDIVO</other_name>
  </intervention>
  <intervention>
    <intervention_type>Combination Product</intervention_type>
    <intervention_name>Trans-arterial tirapazamine embolization</intervention_name>
    <description>Embolization with Lipiodol and Gelfoam</description>
    <arm_group_label>Advanced Hepatocellular carcinoma</arm_group_label>
    <arm_group_label>Metastatic Gastro-esophageal cancer</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        1. Patients with a confirmed diagnosis of (1) advanced HCC or (2) metastatic gastric&#xD;
             cancer.&#xD;
&#xD;
          2. Patients between ages 18 and 80&#xD;
&#xD;
          3. If HCC patients, they should have progressive disease (PD) on the first line immune&#xD;
             therapy for advanced HCC. For patients with metastatic gastric cancer, they should&#xD;
             have failed at least one line of systemic chemotherapy and an immune checkpoint&#xD;
             inhibitor.&#xD;
&#xD;
          4. Patients with at least two liver tumor lesions with at least one with a diameter of 2&#xD;
             cm or bigger, which is amendable for (super-)selective TATE as the target lesion.&#xD;
             Alternatively, patients with one intra-hepatic lesion of 2 cm or bigger and exhapetic&#xD;
             lesion(s) are also acceptable.&#xD;
&#xD;
          5. ECOG score 2 or less&#xD;
&#xD;
          6. Child-Pugh scores 5-7 for HCC patients&#xD;
&#xD;
          7. Patients have normal organ function.&#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>Nadine Abi-Jaoudeh, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>UC Irvine Medical Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Ray Lee, MD PhD</last_name>
    <phone>8043341076</phone>
    <email>ray.lee01@teclison.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>University of California, Irvine</name>
      <address>
        <city>Orange</city>
        <state>California</state>
        <zip>92868</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Cindy D Duong</last_name>
    </contact>
    <investigator>
      <last_name>Nadine Abi-Jaoudeh, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>August 16, 2017</study_first_submitted>
  <study_first_submitted_qc>August 22, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 24, 2017</study_first_posted>
  <last_update_submitted>April 13, 2022</last_update_submitted>
  <last_update_submitted_qc>April 13, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 21, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Hepatocellular carcinoma</keyword>
  <keyword>Immune checkpoint inhibitor</keyword>
  <keyword>Gastric cancer</keyword>
  <keyword>Progression</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma, Hepatocellular</mesh_term>
    <mesh_term>Stomach Neoplasms</mesh_term>
    <mesh_term>Liver Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Nivolumab</mesh_term>
    <mesh_term>Tirapazamine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03259867
org study id: LT-004
nct id: NCT03259867
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This is a multi-center, open-label phase IIA study that investigates the preliminary efficacy
      of Trans-arterial Tirapazamine Embolization (TATE) treatment of liver cancer followed by a
      PD-1 checkpoint inhibitor (nivolumab). Patients with two types of cancers will be enrolled,
      advanced hepatocellular carcinoma (HCC),and metastatic gastric cancer. All enrolled patients
      need to have liver lesions and have progressed on a prior immune checkpoint inhibitor.
The goal of the study is to investigate whether tumor necrosis induced by Trans-arterial
      Tirapazamine Embolization (TATE) treatment can boost anti-tumor immunity and enhance the
      therapeutic efficacy of immune checkpoint inhibitor. Patients with advanced liver cancers
      (primary HCC or metastatic gastric cancer) who have progressed on a prior immune checkpoint
      inhibitor will be enrolled in the study. Liver lesions will be treated with up to 4 TATE
      treatments for optimal debulking, which also serve as a vaccination process toward tumor.
      Lesion not treated with TATE will be used for monitoring the response toward a PD-1 inhibitor
      (Nivolumab) for abscopal effect. If a patient subsequently develops an "escape" to the PD-1
      inhibitor, patient can have another 2 TATE treatments of the escaped tumor lesion. Dosing of
      the PD-1 inhibitor is per standard FDA-approved dosing schedule and continues until
      progressive disease. The efficacy will be assessed by the response rate (RR) using RECIST.
allocation: Non-Randomized
intervention model: Single Group Assignment
intervention model description: One arm for advanced HCC, and one for second line metastatic gastro-esophageal cancer . All enrolled patients will receive the same treatment with TATE and a PD-1 inhibitor (nivolumab) until disease progression
primary purpose: Treatment
masking: None (Open Label)
measure: Overall Response Rate
time frame: up to 24 months
description: Per RECIST 1.1 criteria
measure: Duration of Response
time frame: up to 24 months
description: From the date of image-demonstrated response to the date of progression
measure: Time to Progression
time frame: up to 24 months
description: From randomization to disease progression or death
measure: Progression Free Survival
time frame: up to 24 months
description: From randomization to disease progression or death
measure: Overall survival
time frame: through study completion, an average of 3 years
description: From randomization to death
arm group label: Advanced Hepatocellular carcinoma
arm group type: Experimental
description: PD-1 inhibitor (Nivolumab 480 mg Q4W IV ) starts at day 1, and continues until progression.
TATE treatment starts at day 8 for debulking up to 4 cycles. If escape lesion appears, two more TATE treatments can be given. Tirapazamine dose at 35 mg flat dose given before embolization.
arm group label: Metastatic Gastro-esophageal cancer
arm group type: Experimental
description: PD-1 inhibitor (Nivolumab 480 mg Q4W IV) starts at day 1, and continues until progression.
TATE treatment starts at day 8 for debulking up to 4 cycles. If escape lesion appears, two more TATE treatments can be given. Tirapazamine dose at 35 mg flat dose given before embolization.
intervention type: Drug
intervention name: Nivolumab Injectable Product
description: a PD-1 immune check inhibitor
arm group label: Advanced Hepatocellular carcinoma
arm group label: Metastatic Gastro-esophageal cancer
other name: OPDIVO
intervention type: Combination Product
intervention name: Trans-arterial tirapazamine embolization
description: Embolization with Lipiodol and Gelfoam
arm group label: Advanced Hepatocellular carcinoma
arm group label: Metastatic Gastro-esophageal cancer
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Nadine Abi-Jaoudeh, MD
role: Principal Investigator
affiliation: UC Irvine Medical Center
last name: Ray Lee, MD PhD
phone: 8043341076
email: ray.lee01@teclison.com
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
responsible party type: Sponsor
mesh term: Carcinoma, Hepatocellular
mesh term: Stomach Neoplasms
mesh term: Liver Neoplasms
mesh term: Nivolumab
mesh term: Tirapazamine
sharing ipd: No