<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/NCT04506983</url>
  </required_header>
  <id_info>
    <org_study_id>HXYT-009</org_study_id>
    <nct_id>NCT04506983</nct_id>
  </id_info>
  <brief_title>GPC3-CAR-T Cells for the Hepatocellular Carcinoma</brief_title>
  <official_title>The Phase I Efficacy and Safety Clinical Study of GPC3-CAR-T Cells in Hepatocellular Carcinoma Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Beijing Tsinghua Chang Gung Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>China Immunotech (Beijing) Biotechnology Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Beijing Tsinghua Chang Gung Hospital</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a single center, single arm, open-label, phase I study to evaluate the safety and&#xD;
      efficacy of GPC3-CAR-T cells in patients with hepatocellular carcinoma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      GPC3-CAR-T cells is a novel CAR-T cells which designed for the cell membrane protein&#xD;
      Glypican-3. Patients with hepatocellular carcinoma will be enrolled, and GPC3-CAR-T cells&#xD;
      will be intravenously infused with a escalated dose of 1×106, 3×106, 10×106 GPC3-CAR-T cells.&#xD;
      Tumor markers and GPC3-CAR-T cell proliferation will be monitored in the scheduled time (day&#xD;
      0, day 4, day 7, day 10, day 14, day 28). The aim of this clinical trial is to evaluate the&#xD;
      safety and efficacy of GPC3-CAR-T cells therapy in patients with hepatocellular carcinoma.&#xD;
      The primary endpoint is the safety of CAR-T cells including the effect ratio of CRS and&#xD;
      ICANS, ORR. The secondary endpoint is the CAR-T ratio and CAR gene copied number in PB, PFS,&#xD;
      OS and DOR.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Suspended</overall_status>
  <why_stopped>
    Adjust the plan&#xD;
  </why_stopped>
  <start_date type="Anticipated">June 10, 2022</start_date>
  <completion_date type="Anticipated">October 10, 2023</completion_date>
  <primary_completion_date type="Anticipated">June 10, 2023</primary_completion_date>
  <phase>Phase 1</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>Percentage of adverse events</measure>
    <time_frame>12months</time_frame>
    <description>Percentage of participants with adverse events.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Objective Remission Rate(ORR)</measure>
    <time_frame>12months</time_frame>
    <description>The percentage of participants who achieved complete remission (CR) and partial remission over all participants.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proliferation ratio of CAR-T cells</measure>
    <time_frame>12months</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">12</enrollment>
  <condition>Hepatocellular Carcinoma</condition>
  <arm_group>
    <arm_group_label>GPC3-CAR-T cells</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients with hepatocellular carcinoma will be enrolled, and GPC3-CAR-T cells will be intravenously infused with a escalated dose of 1×106 /3×106/10×106GPC3-CAR-T cells. Tumor markers and GPC3-CAR-T cell proliferation will be monitored in the scheduled time (day 0, day 4, day 7, day 10, day 14,day 21, day 28).</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>GPC3-CAR-T cells</intervention_name>
    <description>Patients with hepatocellular carcinoma will be enrolled, and GPC3-CAR-T cells will be intravenously infused with a escalated dose of 1×106 /3×106/10×106GPC3-CAR-T cells.</description>
    <arm_group_label>GPC3-CAR-T cells</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age ≧18years, gender unlimited.&#xD;
&#xD;
          2. Failure or intolerance after at least first-line treatment.&#xD;
&#xD;
          3. GPC3 positive(IHC)&#xD;
&#xD;
          4. Patients must have at least one target lesion available for evaluation.&#xD;
&#xD;
          5. BCLC B or C.&#xD;
&#xD;
          6. Child-Pugh grade A or B&#xD;
&#xD;
          7. ECOG is 0 or 1 (one week before enrollment.)&#xD;
&#xD;
          8. Estimated life expectancy ≥ 3 months.&#xD;
&#xD;
          9. Functioning of major organs are normal.&#xD;
&#xD;
         10. Women of childbearing age (15-49 years old) must receive a pregnancy test within 7&#xD;
             days prior to initiation of treatment and the results are negative; male and female&#xD;
             patients with fertility must use an effective contraceptive to ensure 3 months after&#xD;
             discontinuation of treatment during the study period not pregnant inside.&#xD;
&#xD;
         11. Patients who voluntarily sign informed consent and are willing to comply with&#xD;
             treatment plans, visit arrangements, laboratory tests and other research procedures.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. There are uncontrollable active infections that need systemic treatment.&#xD;
&#xD;
          2. HIV antibody is positive or syphilis antibody is positive.&#xD;
&#xD;
          3. Pregnant or lactating women.&#xD;
&#xD;
          4. hepatic encephalopathy.&#xD;
&#xD;
          5. patients with organ failure:&#xD;
&#xD;
               -  Heart: NYHA heart function grade IV;&#xD;
&#xD;
               -  Liver: Grade C that achieves Child-Turcotte liver function grading;&#xD;
&#xD;
               -  Kidney: kidney failure and uremia;&#xD;
&#xD;
               -  Lung: symptoms of respiratory failure;&#xD;
&#xD;
               -  Brain: a person with a disability.&#xD;
&#xD;
          6. It is undergoing systemic hormones therapy.&#xD;
&#xD;
          7. Impact results show that over 50% of the liver is occupied by tumor .&#xD;
&#xD;
          8. Patients who are still in the observation stage of other antitumor drugs 30 days&#xD;
             before blood collection.&#xD;
&#xD;
          9. Patients were received other gene therapy products, or are participating in other&#xD;
             clinical trials within 4 weeks prior to cell infusion.&#xD;
&#xD;
         10. Abnormal thyroid function ≧Level 3.&#xD;
&#xD;
         11. Active autoimmune diseases require systemic treatment during the first two years of&#xD;
             screening.&#xD;
&#xD;
         12. Patients have mental illness or history of drug abuse.&#xD;
&#xD;
         13. Patients are participating in other clinical studies.&#xD;
&#xD;
         14. The researchers found that it was unsuitable for the recipients to be enrolled.&#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>Gong Li, M.A.</last_name>
    <role>Study Director</role>
    <affiliation>Beijing Tsinghua Changgeng Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Beijing Tsinghua Changgung Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>January 2022</verification_date>
  <study_first_submitted>August 6, 2020</study_first_submitted>
  <study_first_submitted_qc>August 7, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 10, 2020</study_first_posted>
  <last_update_submitted>January 29, 2022</last_update_submitted>
  <last_update_submitted_qc>January 29, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">February 14, 2022</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>Carcinoma, Hepatocellular</mesh_term>
  </condition_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/NCT04506983
org study id: HXYT-009
nct id: NCT04506983
lead sponsor: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
This is a single center, single arm, open-label, phase I study to evaluate the safety and
      efficacy of GPC3-CAR-T cells in patients with hepatocellular carcinoma.
GPC3-CAR-T cells is a novel CAR-T cells which designed for the cell membrane protein
      Glypican-3. Patients with hepatocellular carcinoma will be enrolled, and GPC3-CAR-T cells
      will be intravenously infused with a escalated dose of 1×106, 3×106, 10×106 GPC3-CAR-T cells.
      Tumor markers and GPC3-CAR-T cell proliferation will be monitored in the scheduled time (day
      0, day 4, day 7, day 10, day 14, day 28). The aim of this clinical trial is to evaluate the
      safety and efficacy of GPC3-CAR-T cells therapy in patients with hepatocellular carcinoma.
      The primary endpoint is the safety of CAR-T cells including the effect ratio of CRS and
      ICANS, ORR. The secondary endpoint is the CAR-T ratio and CAR gene copied number in PB, PFS,
      OS and DOR.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percentage of adverse events
time frame: 12months
description: Percentage of participants with adverse events.
measure: Objective Remission Rate(ORR)
time frame: 12months
description: The percentage of participants who achieved complete remission (CR) and partial remission over all participants.
measure: Proliferation ratio of CAR-T cells
time frame: 12months
arm group label: GPC3-CAR-T cells
arm group type: Experimental
description: Patients with hepatocellular carcinoma will be enrolled, and GPC3-CAR-T cells will be intravenously infused with a escalated dose of 1×106 /3×106/10×106GPC3-CAR-T cells. Tumor markers and GPC3-CAR-T cell proliferation will be monitored in the scheduled time (day 0, day 4, day 7, day 10, day 14,day 21, day 28).
intervention type: Biological
intervention name: GPC3-CAR-T cells
description: Patients with hepatocellular carcinoma will be enrolled, and GPC3-CAR-T cells will be intravenously infused with a escalated dose of 1×106 /3×106/10×106GPC3-CAR-T cells.
arm group label: GPC3-CAR-T cells
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Gong Li, M.A.
role: Study Director
affiliation: Beijing Tsinghua Changgeng Hospital
facility: 
country: China
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Hepatocellular