<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/NCT04417764</url>
  </required_header>
  <id_info>
    <org_study_id>CellTransplant&amp;GeneTherapy2020</org_study_id>
    <nct_id>NCT04417764</nct_id>
  </id_info>
  <brief_title>TACE Combined With PD-1 Knockout Engineered T Cell in Advanced Hepatocellular Carcinoma.</brief_title>
  <official_title>Safety and Effect Assessment of TACE in Combination With Autologous PD-1 Knockout Engineered T Cells by Percutaneous Infusion in the Paitents With Advanced Hepatocellular Carcinoma.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Central South University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Central South University</source>
  <oversight_info>
    <has_dmc>No</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>
      This study will evaluate the safety and effect of transcatheter arterial chemoembolization&#xD;
      (TACE)combined with percutaneous transhepatic PD-1 knockout engineered T cell infusion in the&#xD;
      Paitents with advanced hepatocellular carcinoma(HCC). Blood and tissue samples will also be&#xD;
      collected for research purposes.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a clinical study to investigate the safety and effect of transcatheter arterial&#xD;
      chemoembolization (TACE) in combination with PD-1 knockout engineered T cells in the Paitents&#xD;
      with advanced hepatocellular carcinoma. TACE would block the blood supply of the tumor to&#xD;
      achieve ischemic, hypoxic andnecrotic effects. The PD-1 knockout engineered T cells were also&#xD;
      prepared from autologous origin using CRISPR Cas9 technology. The patients performed one TACE&#xD;
      treatment followed by 3 cycles of PD-1 edited T cells by percutaneous infusion in the&#xD;
      peripheral of tumor under the guide of CT every four weeks. The safety and clinical efficacy&#xD;
      will be evaluated. biomarkers and immunological markers will be monitored.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">June 20, 2019</start_date>
  <completion_date type="Anticipated">December 31, 2024</completion_date>
  <primary_completion_date type="Anticipated">December 30, 2024</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>Incidence of Adverse Events</measure>
    <time_frame>up to 2 years</time_frame>
    <description>Number of participants with Adverse Events using Common Terminology Criteria for Adverse Events (CTCAE v4.03) in patients.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Response Rate</measure>
    <time_frame>up to 12 months</time_frame>
    <description>To evaluate the objective response rate (ORR) ,refers to the proportion of patients whose tumors shrink to a certain extent and remain unchanged for a certain period of time, including patients with CR+PR.Tumors are assessed at baseline, the 8th week, the 16th week,the 24th week, and once every 12 weeks during the treatment and follow-up period per RECIST1.1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to First Response</measure>
    <time_frame>up to 2 years</time_frame>
    <description>To evaluate time to first response, defined as the time from the first cell infusion to the first observed complete response (CR) or partial response (PR).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response</measure>
    <time_frame>up to 2 years</time_frame>
    <description>To evaluate the duration of response (DOR), defined as the time from the first observed CR or PR to the first observed PD or death from any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival</measure>
    <time_frame>up to 2 years</time_frame>
    <description>To evaluate the progression free survival (PFS), defined as the time from the first cell infusion to the first observed PD or death from any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>up to 2 years</time_frame>
    <description>To evaluate the overall survival (OS), defined as the time from the first cell infusion to death.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">10</enrollment>
  <condition>Advanced Hepatocellular Carcinoma</condition>
  <arm_group>
    <arm_group_label>TACE combined PD-1 knockout T cell treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Transcatheter arterial chemoembolization</intervention_name>
    <description>The patients are plan to operated by Transcatheter arterial chemoembolization(TACE).</description>
    <arm_group_label>TACE combined PD-1 knockout T cell treatment</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>PD-1 knockout engineered T cells</intervention_name>
    <description>The PD-1 knockout engineered T cells are prepared from autologous origin using CRISPR Cas9 technology. The patients are plan to receive 3 or more cycles of PD-1 knockout engineered T cells infusion by percutaneous fine needle liver puncture with a 4-weeks interval. A total of 1 to 3× 10^9 PD-1 edited T cells will be infused each cycle. Patients continued receiving treatment unless they had unacceptable adverse effects, or progressive disease confirmed by CT or they withdrew consent.</description>
    <arm_group_label>TACE combined PD-1 knockout T cell treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients with unresectable hepatocellular carcinoma;&#xD;
&#xD;
          2. More than 18 years old;&#xD;
&#xD;
          3. Patients diagnosed with hepatocellular carcinoma by histopathology or imagings;&#xD;
&#xD;
          4. Liver function ChildPugh ≤7 points, Physical strength score ECOG-pts 0-1 points;&#xD;
&#xD;
          5. Maximum tumor diameter ≤10cm, tumor number ≤10, no vascular invasion or extrahepatic&#xD;
             metastasis;&#xD;
&#xD;
          6. Other organs of the whole body function well;&#xD;
&#xD;
          7. Sign the informed consent;&#xD;
&#xD;
          8. Passed the review by the ethics committee.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Less than 18 or more than 70 years old;&#xD;
&#xD;
          2. Lack of autonomous decision-making ability;&#xD;
&#xD;
          3. ECOG score &gt;2, cachexia or multiple organ failure;&#xD;
&#xD;
          4. Metastases; The tumor was diffuse or metastasized widely and the expected survival&#xD;
             time was less than 3 months.&#xD;
&#xD;
          5. Uncorrectable coagulation dysfunction with a history of bleeding; Organ transplant;&#xD;
&#xD;
          6. Patients with severe autoimmune diseases; Iodine contrast agent allergy; High allergic&#xD;
             constitution;&#xD;
&#xD;
          7. The main portal vein was completely blocked by cancer embolism, with little collateral&#xD;
             vascular formation;&#xD;
&#xD;
          8. Severe infection; AIDS, syphilis infection;&#xD;
&#xD;
          9. T cell lymphoma;&#xD;
&#xD;
         10. Patients with mental illness, severe trauma or other stress conditions;&#xD;
&#xD;
         11. Pregnant or nursing women;&#xD;
&#xD;
         12. Abnormal peripheral blood routine detection;&#xD;
&#xD;
         13. Failing to comply with the study protocol to complete the diagnosis and treatment&#xD;
             project; Failed ethics committee review.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Wei Wang, MD</last_name>
    <phone>86-0731-88618411</phone>
    <email>cjr.wangwei@vip.163.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>The 3rd Xiangya Hospital of Central South University</name>
      <address>
        <city>Changsha</city>
        <state>Hunan</state>
        <zip>410013</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Xiaoqian Ma, MD</last_name>
      <phone>86-0731-88618413</phone>
      <email>85316745@qq.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>May 29, 2020</study_first_submitted>
  <study_first_submitted_qc>June 2, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 5, 2020</study_first_posted>
  <last_update_submitted>February 7, 2023</last_update_submitted>
  <last_update_submitted_qc>February 7, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 9, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Central South University</investigator_affiliation>
    <investigator_full_name>Wei Wang,MD</investigator_full_name>
    <investigator_title>Principal for The Institute for Cell Transplantation and Gene Therapy</investigator_title>
  </responsible_party>
  <keyword>CRISPR Cas 9</keyword>
  <keyword>TACE</keyword>
  <keyword>PD-1 knockout engineered T cells</keyword>
  <keyword>Advanced hepatocellular carcinoma</keyword>
  <keyword>Locally administered treatment</keyword>
  <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/NCT04417764
org study id: CellTransplant&GeneTherapy2020
nct id: NCT04417764
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study will evaluate the safety and effect of transcatheter arterial chemoembolization
      (TACE)combined with percutaneous transhepatic PD-1 knockout engineered T cell infusion in the
      Paitents with advanced hepatocellular carcinoma(HCC). Blood and tissue samples will also be
      collected for research purposes.
This is a clinical study to investigate the safety and effect of transcatheter arterial
      chemoembolization (TACE) in combination with PD-1 knockout engineered T cells in the Paitents
      with advanced hepatocellular carcinoma. TACE would block the blood supply of the tumor to
      achieve ischemic, hypoxic andnecrotic effects. The PD-1 knockout engineered T cells were also
      prepared from autologous origin using CRISPR Cas9 technology. The patients performed one TACE
      treatment followed by 3 cycles of PD-1 edited T cells by percutaneous infusion in the
      peripheral of tumor under the guide of CT every four weeks. The safety and clinical efficacy
      will be evaluated. biomarkers and immunological markers will be monitored.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence of Adverse Events
time frame: up to 2 years
description: Number of participants with Adverse Events using Common Terminology Criteria for Adverse Events (CTCAE v4.03) in patients.
measure: Response Rate
time frame: up to 12 months
description: To evaluate the objective response rate (ORR) ,refers to the proportion of patients whose tumors shrink to a certain extent and remain unchanged for a certain period of time, including patients with CR+PR.Tumors are assessed at baseline, the 8th week, the 16th week,the 24th week, and once every 12 weeks during the treatment and follow-up period per RECIST1.1.
measure: Time to First Response
time frame: up to 2 years
description: To evaluate time to first response, defined as the time from the first cell infusion to the first observed complete response (CR) or partial response (PR).
measure: Duration of Response
time frame: up to 2 years
description: To evaluate the duration of response (DOR), defined as the time from the first observed CR or PR to the first observed PD or death from any cause.
measure: Progression Free Survival
time frame: up to 2 years
description: To evaluate the progression free survival (PFS), defined as the time from the first cell infusion to the first observed PD or death from any cause.
measure: Overall Survival
time frame: up to 2 years
description: To evaluate the overall survival (OS), defined as the time from the first cell infusion to death.
arm group label: TACE combined PD-1 knockout T cell treatment
arm group type: Experimental
intervention type: Procedure
intervention name: Transcatheter arterial chemoembolization
description: The patients are plan to operated by Transcatheter arterial chemoembolization(TACE).
arm group label: TACE combined PD-1 knockout T cell treatment
intervention type: Biological
intervention name: PD-1 knockout engineered T cells
description: The PD-1 knockout engineered T cells are prepared from autologous origin using CRISPR Cas9 technology. The patients are plan to receive 3 or more cycles of PD-1 knockout engineered T cells infusion by percutaneous fine needle liver puncture with a 4-weeks interval. A total of 1 to 3× 10^9 PD-1 edited T cells will be infused each cycle. Patients continued receiving treatment unless they had unacceptable adverse effects, or progressive disease confirmed by CT or they withdrew consent.
arm group label: TACE combined PD-1 knockout T cell treatment
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Wei Wang, MD
phone: 86-0731-88618411
email: cjr.wangwei@vip.163.com
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Central South University
investigator full name: Wei Wang,MD
investigator title: Principal for The Institute for Cell Transplantation and Gene Therapy
mesh term: Carcinoma
mesh term: Carcinoma, Hepatocellular