<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/NCT03252808</url>
  </required_header>
  <id_info>
    <org_study_id>TBI1401-03</org_study_id>
    <nct_id>NCT03252808</nct_id>
  </id_info>
  <brief_title>Phase I Study of TBI-1401(HF10) Plus Chemotherapy in Patients With Unresectable Pancreatic Cancer.</brief_title>
  <official_title>Phase I Study of Combination With TBI-1401(HF10), a Replication-competent HSV-1 Oncolytic Virus, and Chemotherapy in Patients With Stage III or IV Unresectable Pancreatic Cancer.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Takara Bio Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Takara Bio Inc.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine the recommended dose of TBI-1401(HF10) treatment in&#xD;
      combination with chemotherapy (Gemcitabine + Nab-paclitaxel or TS-1) in patients with stage&#xD;
      III or IV unresectable pancreatic cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A Phase I, open-label, multi-center study to determine the recommended dose of TBI-1401(HF10)&#xD;
      treatment in combination with chemotherapy (Gemcitabine + Nab-paclitaxel or TS-1) in patients&#xD;
      with stage III or IV unresectable pancreatic cancer. Patients with stage IV must failed a&#xD;
      gemcitabine based first-line chemotherapy.&#xD;
&#xD;
      Patients with stage III will receive the repeated intratumoral injection of TBI-1401(HF10) at&#xD;
      recommended dose at 2-week intervals in combination with intravenous infusion of 1000 mg/m^2&#xD;
      Gemcitabine and 125 mg/m^2 Nab-paclitaxel at weekly for 3 weeks followed by 1 week rest.&#xD;
&#xD;
      Patients with stage IV will receive the repeated intratumoral injection of TBI-1401(HF10) at&#xD;
      recommended dose at 2-week intervals in combination with oral of 40 - 60 mg TS-1 at twice&#xD;
      daily for 4 weeks followed by 2 weeks rest.&#xD;
&#xD;
      Patients will receive the combination therapy of TBI-1401(HF10) + chemo for up to 1 year if&#xD;
      eligible for treatment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">September 25, 2017</start_date>
  <completion_date type="Anticipated">March 31, 2035</completion_date>
  <primary_completion_date type="Actual">February 19, 2020</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Dose Limiting Toxicity (DLT)</measure>
    <time_frame>Through 1st TBI-1401(HF10) injection to before 3rd injection (basically 4 weeks).</time_frame>
    <description>Determine the recommended dose of TBI-1401(HF10) in combination with Gemcitabine and Nab-paclitaxel.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Adverse Events (AEs)</measure>
    <time_frame>Through 1st TBI-1401(HF10) injection to study completion (up to 13 month).</time_frame>
    <description>Evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE version 4.0).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective response rate (ORR) by RECIST</measure>
    <time_frame>At 16 weeks and through study completion (up to 1 year).</time_frame>
    <description>Overall tumor response evaluated by RECIST version 1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective response rate (ORR) by irRECIST</measure>
    <time_frame>At 16 weeks and through study completion (up to 1 year).</time_frame>
    <description>Overall tumor response evaluated by irRECIST.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival (PFS) by RECIST</measure>
    <time_frame>Through disease progression (up to 1 year).</time_frame>
    <description>Evaluation the time to progression during and after the treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival (PFS) by irRECIST</measure>
    <time_frame>Through disease progression (up to 1 year).</time_frame>
    <description>Evaluation the time to progression during and after the treatment.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>From 1st treatment to death (up to 2 years).</time_frame>
    <description>Evaluation the overall survival.</description>
  </other_outcome>
  <other_outcome>
    <measure>1 year survival rate</measure>
    <time_frame>for 1 year.</time_frame>
    <description>Determine the 1 year survival rate of patient who received treatment.</description>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">36</enrollment>
  <condition>Pancreatic Cancer Stage III</condition>
  <condition>Pancreatic Cancer Stage IV</condition>
  <arm_group>
    <arm_group_label>TBI-1401(HF10) + Gem/nab-PTX</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>1x10^6 or 1x10^7 TCID50/mL TBI-1401(HF10) administered to the tumor in a total volume up to 2.0 mL (injection volume will be adjusted based on the tumor size) by EUS-guided intratumoral injection and 1000 mg/m^2 Gemcitabine and 125 mg/m^2 Nab-paclitaxel injected by intravenous infusions.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>TBI-1401(HF10) + TS-1 (primary)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>1x10^6 or 1x10^7 TCID50/mL TBI-1401(HF10) administered to the primary tumor in a total volume up to 2.0 mL (injection volume will be adjusted based on the tumor size) by EUS-guided intratumoral injection and TS-1 administered by oral.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>TBI-1401(HF10) + TS-1 (primary and meta)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>1x10^6 or 1x10^7 TCID50/mL TBI-1401(HF10) administered to the primary tumor in a total volume up to 2.0 mL (injection volume will be adjusted based on the tumor size) by EUS-guided intratumoral injection and hepatic metastasis in a total volume up to 2.0 mL (injection volume will be adjusted based on the tumor size) by EUS-guided intratumoral injection or percutaneous injection and TS-1 administered by oral.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>TBI-1401(HF10)</intervention_name>
    <description>1x10^6 or 1x10^7 TCID50/mL TBI-1401(HF10) administered by intratumoral injection at 2-week intervals. Patients may continue to receive the injections for up to 1 year if eligible for injection.</description>
    <arm_group_label>TBI-1401(HF10) + Gem/nab-PTX</arm_group_label>
    <arm_group_label>TBI-1401(HF10) + TS-1 (primary and meta)</arm_group_label>
    <arm_group_label>TBI-1401(HF10) + TS-1 (primary)</arm_group_label>
    <other_name>HF10</other_name>
    <other_name>canerpaturev</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Gemcitabine</intervention_name>
    <description>1000 mg/m^2 Gemcitabine administered by intravenous infusion at weekly for 3 weeks followed by a week of rest.</description>
    <arm_group_label>TBI-1401(HF10) + Gem/nab-PTX</arm_group_label>
    <other_name>Gemzar</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nab-paclitaxel</intervention_name>
    <description>125 mg/m^2 Nab-paclitaxel administered by intravenous infusion at weekly for 3 weeks followed by a week of rest.</description>
    <arm_group_label>TBI-1401(HF10) + Gem/nab-PTX</arm_group_label>
    <other_name>Abraxane</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TS-1</intervention_name>
    <description>TS-1 (40-60 mg per body surface area) administered by oral at twice daily for 4 weeks followed by 2 weeks of rest.</description>
    <arm_group_label>TBI-1401(HF10) + TS-1 (primary and meta)</arm_group_label>
    <arm_group_label>TBI-1401(HF10) + TS-1 (primary)</arm_group_label>
    <other_name>Tegafur-gimeracil-oteracil potassium</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with histologically or cytologically confirmed unresectable pancreatic cancer&#xD;
             (stage III or IV) based on the General Rules for the Study of Pancreatic Cancer (The&#xD;
             7th edition), and never received anti-cancer therapy (radiation therapy, chemotherapy,&#xD;
             immunotherapy, surgery, clinical trials).&#xD;
&#xD;
          -  Patients with primary lesion will be intratumorally injectable for TBI-1401(HF10) by&#xD;
             EUS (endoscopic ultrasound).&#xD;
&#xD;
          -  Patients must be ≧20 years of age.&#xD;
&#xD;
          -  Patients must have at least one measurable lesion evaluated by Computed Tomography&#xD;
             (CT) scan on RECIST ver.1.1 at pre-treatment.&#xD;
&#xD;
          -  Patients must have a life expectancy ≧12 weeks.&#xD;
&#xD;
          -  Patients must have an ECOG PS (Eastern Cooperative Oncology Group Performance Status)&#xD;
             of 0-1.&#xD;
&#xD;
          -  Patients demonstrated adequate organ function (≦7 days prior to treatment).&#xD;
&#xD;
          -  Females of childbearing potential must have a negative urine or serum pregnancy test&#xD;
             within 1 week prior to start of treatment.&#xD;
&#xD;
          -  Patients must be able to understand the study and willing to sign a written informed&#xD;
             consent document.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients receiving anti-herpes medication within 1 week prior to TBI-1401(HF10)&#xD;
             treatment (except local treatment such as ointment).&#xD;
&#xD;
          -  Patients with a significant tumor bleeding or coagulation abnormality that could not&#xD;
             treat intratumoral injection or biopsy in safe.&#xD;
&#xD;
          -  Patients with clinically evident Hepatitis B surface antigen (HBs) positive, Hepatitis&#xD;
             C virus (HCV) antibody positive and HSV-RNA positive, Human Immunodeficiency Virus&#xD;
             (HIV) antibody positive.&#xD;
&#xD;
          -  Patients with the active symptom of Epstein-Barr virus (EBV) infection.&#xD;
&#xD;
          -  Patients with active CNS metastases.&#xD;
&#xD;
          -  Patients with ascites, except acceptable mild ascites.&#xD;
&#xD;
          -  Patients with multiple cancer.&#xD;
&#xD;
          -  Patients need to treat anticoagulant or antiplatelet agent.&#xD;
&#xD;
          -  Patients has a history of allergy for CT contrast agent, live vaccine, any drug&#xD;
             excipients, Nab-paclitaxel, Gemcitabine, or any study drugs.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Takara Bio Inc.</last_name>
    <role>Study Director</role>
    <affiliation>Clinical Development &amp; Strategy Division 2</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Clinical Site</name>
      <address>
        <city>Nagoya</city>
        <state>Aichi</state>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Site</name>
      <address>
        <city>Kashiwa</city>
        <state>Chiba</state>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Site</name>
      <address>
        <city>Yokohama</city>
        <state>Kanagawa</state>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Site</name>
      <address>
        <city>Chūōku</city>
        <state>Tokyo</state>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Site</name>
      <address>
        <city>Koto-Ku</city>
        <state>Tokyo</state>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Site</name>
      <address>
        <city>Chiba</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Site</name>
      <address>
        <city>Nagoya</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Site</name>
      <address>
        <city>Osaka</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Japan</country>
  </location_countries>
  <verification_date>June 2022</verification_date>
  <study_first_submitted>August 9, 2017</study_first_submitted>
  <study_first_submitted_qc>August 16, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 17, 2017</study_first_posted>
  <last_update_submitted>June 15, 2022</last_update_submitted>
  <last_update_submitted_qc>June 15, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">June 21, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Unresectable pancreatic cancer</keyword>
  <keyword>Metastatic pancreatic cancer</keyword>
  <keyword>Pancreatic adenocarcinoma</keyword>
  <keyword>TBI-1401(HF10)</keyword>
  <keyword>HF10</keyword>
  <keyword>Oncolytic virus</keyword>
  <keyword>Oncolytic viral immunotherapy</keyword>
  <keyword>Gemcitabine</keyword>
  <keyword>Nab-paclitaxel</keyword>
  <keyword>Albumin-bound paclitaxel</keyword>
  <keyword>Abraxane</keyword>
  <keyword>Tegafur-gimeracil-oteracil potassium</keyword>
  <keyword>TS-1</keyword>
  <keyword>canerpaturev</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pancreatic Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Paclitaxel</mesh_term>
    <mesh_term>Gemcitabine</mesh_term>
    <mesh_term>Tegafur</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/NCT03252808
org study id: TBI1401-03
nct id: NCT03252808
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to determine the recommended dose of TBI-1401(HF10) treatment in
      combination with chemotherapy (Gemcitabine + Nab-paclitaxel or TS-1) in patients with stage
      III or IV unresectable pancreatic cancer.
A Phase I, open-label, multi-center study to determine the recommended dose of TBI-1401(HF10)
      treatment in combination with chemotherapy (Gemcitabine + Nab-paclitaxel or TS-1) in patients
      with stage III or IV unresectable pancreatic cancer. Patients with stage IV must failed a
      gemcitabine based first-line chemotherapy.

      Patients with stage III will receive the repeated intratumoral injection of TBI-1401(HF10) at
      recommended dose at 2-week intervals in combination with intravenous infusion of 1000 mg/m^2
      Gemcitabine and 125 mg/m^2 Nab-paclitaxel at weekly for 3 weeks followed by 1 week rest.

      Patients with stage IV will receive the repeated intratumoral injection of TBI-1401(HF10) at
      recommended dose at 2-week intervals in combination with oral of 40 - 60 mg TS-1 at twice
      daily for 4 weeks followed by 2 weeks rest.

      Patients will receive the combination therapy of TBI-1401(HF10) + chemo for up to 1 year if
      eligible for treatment.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Dose Limiting Toxicity (DLT)
time frame: Through 1st TBI-1401(HF10) injection to before 3rd injection (basically 4 weeks).
description: Determine the recommended dose of TBI-1401(HF10) in combination with Gemcitabine and Nab-paclitaxel.
measure: Adverse Events (AEs)
time frame: Through 1st TBI-1401(HF10) injection to study completion (up to 13 month).
description: Evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE version 4.0).
measure: Objective response rate (ORR) by RECIST
time frame: At 16 weeks and through study completion (up to 1 year).
description: Overall tumor response evaluated by RECIST version 1.1
measure: Objective response rate (ORR) by irRECIST
time frame: At 16 weeks and through study completion (up to 1 year).
description: Overall tumor response evaluated by irRECIST.
measure: Progression-free survival (PFS) by RECIST
time frame: Through disease progression (up to 1 year).
description: Evaluation the time to progression during and after the treatment.
measure: Progression-free survival (PFS) by irRECIST
time frame: Through disease progression (up to 1 year).
description: Evaluation the time to progression during and after the treatment.
measure: Overall survival (OS)
time frame: From 1st treatment to death (up to 2 years).
description: Evaluation the overall survival.
measure: 1 year survival rate
time frame: for 1 year.
description: Determine the 1 year survival rate of patient who received treatment.
arm group label: TBI-1401(HF10) + Gem/nab-PTX
arm group type: Experimental
description: 1x10^6 or 1x10^7 TCID50/mL TBI-1401(HF10) administered to the tumor in a total volume up to 2.0 mL (injection volume will be adjusted based on the tumor size) by EUS-guided intratumoral injection and 1000 mg/m^2 Gemcitabine and 125 mg/m^2 Nab-paclitaxel injected by intravenous infusions.
arm group label: TBI-1401(HF10) + TS-1 (primary)
arm group type: Experimental
description: 1x10^6 or 1x10^7 TCID50/mL TBI-1401(HF10) administered to the primary tumor in a total volume up to 2.0 mL (injection volume will be adjusted based on the tumor size) by EUS-guided intratumoral injection and TS-1 administered by oral.
arm group label: TBI-1401(HF10) + TS-1 (primary and meta)
arm group type: Experimental
description: 1x10^6 or 1x10^7 TCID50/mL TBI-1401(HF10) administered to the primary tumor in a total volume up to 2.0 mL (injection volume will be adjusted based on the tumor size) by EUS-guided intratumoral injection and hepatic metastasis in a total volume up to 2.0 mL (injection volume will be adjusted based on the tumor size) by EUS-guided intratumoral injection or percutaneous injection and TS-1 administered by oral.
intervention type: Biological
intervention name: TBI-1401(HF10)
description: 1x10^6 or 1x10^7 TCID50/mL TBI-1401(HF10) administered by intratumoral injection at 2-week intervals. Patients may continue to receive the injections for up to 1 year if eligible for injection.
arm group label: TBI-1401(HF10) + Gem/nab-PTX
arm group label: TBI-1401(HF10) + TS-1 (primary and meta)
arm group label: TBI-1401(HF10) + TS-1 (primary)
other name: HF10
other name: canerpaturev
intervention type: Drug
intervention name: Gemcitabine
description: 1000 mg/m^2 Gemcitabine administered by intravenous infusion at weekly for 3 weeks followed by a week of rest.
arm group label: TBI-1401(HF10) + Gem/nab-PTX
other name: Gemzar
intervention type: Drug
intervention name: Nab-paclitaxel
description: 125 mg/m^2 Nab-paclitaxel administered by intravenous infusion at weekly for 3 weeks followed by a week of rest.
arm group label: TBI-1401(HF10) + Gem/nab-PTX
other name: Abraxane
intervention type: Drug
intervention name: TS-1
description: TS-1 (40-60 mg per body surface area) administered by oral at twice daily for 4 weeks followed by 2 weeks of rest.
arm group label: TBI-1401(HF10) + TS-1 (primary and meta)
arm group label: TBI-1401(HF10) + TS-1 (primary)
other name: Tegafur-gimeracil-oteracil potassium
criteria: 
gender: All
minimum age: 20 Years
maximum age: N/A
healthy volunteers: No
last name: Takara Bio Inc.
role: Study Director
affiliation: Clinical Development & Strategy Division 2
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Japan
responsible party type: Sponsor
mesh term: Pancreatic Neoplasms
mesh term: Paclitaxel
mesh term: Gemcitabine
mesh term: Tegafur
sharing ipd: No