xml: <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/NCT05962450</url>
    </required_header>
    <id_info>
      <org_study_id>Beijing YouAn Ethics [2023]060</org_study_id>
      <nct_id>NCT05962450</nct_id>
    </id_info>
    <brief_title>Adoptive Autologous iNKT Cells for the Treatment of Progressed Hepatocellular Carcinoma Continuing on PD-1 Inhibitor Therapy</brief_title>
    <official_title>An Open Label, Randomized, Controlled, Clinical Trial of Adoptive Autologous Invariant Natural Killer T Cells for the Treatment of Progressed Hepatocellular Carcinoma Continuing on PD-1 Inhibitor Therapy</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Beijing YouAn Hospital</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Beijing Gene Key Life Technology Co., Ltd.</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Beijing YouAn Hospital</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 goal of this clinical trial is to explore the efficacy and safety of autologous iNKT&#xD;
        cells in patients with progressed hepatocellular carcinoma (HCC) after treatment with PD-1&#xD;
        antibody. The main question it aims to answer are:&#xD;
  &#xD;
          -  the efficacy of autologous iNKT cells in patients with progressed HCC after treatment&#xD;
             with PD-1 antibody.&#xD;
  &#xD;
          -  the safety of autologous iNKT cells in patients with progressed HCC after treatment with&#xD;
             PD-1 antibody.&#xD;
  &#xD;
        Participants will be randomized 1:1 to receive Regorafenib + PD-1 + iNKT cells (RPI group) or&#xD;
        the treatment of Regorafenib + PD-1 (RP group).&#xD;
  &#xD;
        Researchers will compare RPI group and RP group to see whether the iNKT cells can achieve a&#xD;
        better therapeutic effect on HCC patients with PD-1 resistance.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Single center, randomized, open trial in Barcelona Clinic Liver Cancer（BCLC）C stage patients&#xD;
        with progressed HCC after anti-angiogenic targeted drugs combined with PD-1 monoclonal&#xD;
        antibody therapy to explore the efficacy and safety of autologous iNKT cells.&#xD;
  &#xD;
        This study includes screening period, treatment period and follow-up period (until the&#xD;
        subjects withdrew their informed consent or received other anti-tumor therapy or participated&#xD;
        in other clinical trials or the researchers judged that it is not in the best interests of&#xD;
        patients to continue to participate in the study) after treatment.&#xD;
  &#xD;
        The patients will be randomized 1:1 using a random number table to receive Regorafenib + PD-1&#xD;
        + iNKT cells (RPI group) or the treatment of Regorafenib + PD-1 (RP group).&#xD;
  &#xD;
          1. iNKT Cells：Intravenous infusion. The cells will be infused every two weeks as a course&#xD;
             of treatment for up to six courses.&#xD;
  &#xD;
          2. PD-1：Intravenous infusion, according to the drug instructions.&#xD;
  &#xD;
          3. Regorafenib：Oral administration, according to the drug instructions. All target and&#xD;
             non-target lesions will be assessed by chest, abdomen, and pelvis CT or MRI at baseline&#xD;
             and every 8 weeks until radiological progression (according to mRECIST/iRECIST).&#xD;
  &#xD;
        Safety and side-effect profiles will be assessed based on the nature, frequency, and severity&#xD;
        of adverse events, according to the National Cancer Institute (NCI) Common Terminology&#xD;
        Criteria for Adverse Events (CTCAE), version 5.0.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">August 1, 2023</start_date>
    <completion_date type="Anticipated">August 1, 2025</completion_date>
    <primary_completion_date type="Anticipated">August 1, 2025</primary_completion_date>
    <phase>Phase 2</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>
      <masking_description>Block randomization was performed by the independent masked statistician. Two independent masked radiologist who are blinded to patients' clinical information will review the imaging examinations.</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>Progression-Free Survival (PFS)</measure>
      <time_frame>The time from enrollment to disease progression, or death from any cause, whichever occurred first, up to 24 months.</time_frame>
      <description>The time from enrollment to disease progression according to the modified RECIST (mRECIST) guideline in trial immunotherapeutics, or death from any cause, whichever occurred first；the time from enrollment to confirmed disease progression (iCPD) according to the iRECIST</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Disease control rate (DCR)</measure>
      <time_frame>Evaluation was performed every 8 weeks after the start of the treatment, up to 24 months.</time_frame>
      <description>including complete response (CR), partial response (PR), and disease stabilization (SD), evaluated by imaging according to iRECIST for target lesions and assessed by MRI/CT.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Objective response rate (ORR)</measure>
      <time_frame>Evaluation was performed every 8 weeks after the start of the treatment, up to 24 months.</time_frame>
      <description>complete response (CR) and partial response (PR) evaluated by imaging according to mRECIST/iRECIST for target lesions and assessed by MRI/CT.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall survival (OS)</measure>
      <time_frame>Time from the date of enrollment to the date of death from any cause, up to 36 months.</time_frame>
      <description>Time from the date of enrollment to the date of death from any cause.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>1-year overall survival rate (1-year OS rate)</measure>
      <time_frame>Time from the date of enrollment to 1 year later.</time_frame>
      <description>The proportion of subjects who were still alive from the date of enrollment to 1 year later</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Duration of Overall Response (DOR)</measure>
      <time_frame>Time from the first tumor remission to the first recording of disease progression or death from any cause, up to 24 months..</time_frame>
      <description>The time from the first tumor remission (CR or PR according to mRECIST/iRECIST) to the first recording of disease progression (PD according to mRECIST criteria or iCPD according to iRECIST) or death from any cause (whichever occurs first).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Time to progression (TTP)</measure>
      <time_frame>Time from the date of enrollment to the date of first disease progression, up to 24 months.</time_frame>
      <description>Time from the date of enrollment to the date of first disease progression (PD) according to mRECIST or iCPD according to iRECIST).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Time to Quality of Life (QoL) Deterioration</measure>
      <time_frame>Time from the date of enrollment, up to 24 months.</time_frame>
      <description>EORTC QLQ-C30: European Organization for Research on Treatment of Cancer Quality of Life Questionnare-Core 30.&#xD;
  The totally 30 items spread out over five functional scales (15 items), three symptom scales (7 items), a global health status/QoL scale (2 items), and six single items. 1-28 item ranges 1: not at all, 2: a little, 3: quite a lit, 4: very much; 29-30 item ranges 1-7 from very poor to excellent. Raw score (RS) is an average of all items in each area. Standardized score is in the range of 0-100 by formula SS=[1-(RS-1)/n] x100 (function) or SS=[（RS-1）/n]x100 (symptom or overall health) respectively. A high scale score represents a higher/healthy response level.&#xD;
  Time to deterioration was defined as a decrease from baseline of 10 points or more on the EORTC QLQ-C30 maintained for two consecutive assessments.</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">84</enrollment>
    <condition>Hepatocellular Carcinoma</condition>
    <arm_group>
      <arm_group_label>RPI group</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Regorafenib + PD-1 + iNKT cells</description>
    </arm_group>
    <arm_group>
      <arm_group_label>RP group</arm_group_label>
      <arm_group_type>Other</arm_group_type>
      <description>Regorafenib + PD-1</description>
    </arm_group>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>iNKT Cells</intervention_name>
      <description>the iNKT cells will be intravenous infused every two weeks as a course of treatment for up to six courses , the reinfusion dose is determined according to the patient's body surface area, which was about 108~109cells/m2.</description>
      <arm_group_label>RPI group</arm_group_label>
      <other_name>Vα24+ T Cells</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>PD-1</intervention_name>
      <description>Intravenous infusion, according to the drug instructions.</description>
      <arm_group_label>RP group</arm_group_label>
      <arm_group_label>RPI group</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Regorafenib</intervention_name>
      <description>Oral administration, according to the drug instructions.</description>
      <arm_group_label>RP group</arm_group_label>
      <arm_group_label>RPI group</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  18-75 years of age.&#xD;
  &#xD;
            -  Barcelona Clinic Liver Cancer（BCLC） C stage hepatocellular carcinoma (HCC) confirmed&#xD;
               by CT, MRI, and/or histopathology.&#xD;
  &#xD;
            -  Progressed after receiving anti-angiogenic targeted drugs combined with PD-1&#xD;
               monoclonal antibody.&#xD;
  &#xD;
            -  Life expectancy of at least 12 weeks.&#xD;
  &#xD;
            -  Child-Pugh A/B.&#xD;
  &#xD;
            -  Voluntary signing of informed consent.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  History of severe hypertension or cardiac disease.&#xD;
  &#xD;
            -  known central nervous system (CNS) tumor or combined with other malignant disorders.&#xD;
  &#xD;
            -  Uncontrolled immune system or infectious disease.&#xD;
  &#xD;
            -  Known history of the human immunodeficiency virus (HIV) or syphilis infection.&#xD;
  &#xD;
            -  History of stem cell transplant or organ allograft.&#xD;
  &#xD;
            -  History of allergy to immunotherapy or related drugs.&#xD;
  &#xD;
            -  Bilirubin is twice times the upper limit of normal.&#xD;
  &#xD;
            -  Glomerular filtration rate （GFR）&lt; 60ml/min.&#xD;
  &#xD;
            -  Serious complications include moderate or severe infective pleural and peritoneal&#xD;
               effusion, pericardial effusion, upper gastrointestinal bleeding, hepatic&#xD;
               encephalopathy.&#xD;
  &#xD;
            -  Pregnancy or lactation.&#xD;
  &#xD;
            -  History of severe allergy to any monoclonal antibody or anti-angiogenic targeted drug.&#xD;
  &#xD;
            -  Deemed not suitable for cellular immunotherapy by the investigators.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>75 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Jun Lu, MD.</last_name>
      <role>Principal Investigator</role>
      <affiliation>Beijing YouAn Hospital</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Jun Lu, MD.</last_name>
      <phone>86-13661381489</phone>
      <email>lujun98@ccmu.edu.cn</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Songtao Liu, MD.</last_name>
      <phone>86-13811120755</phone>
      <email>botao8080@163.com</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Beijing Youan Hospital,Capital Medical University</name>
        <address>
          <city>Beijing</city>
          <state>Beijing</state>
          <zip>100069</zip>
          <country>China</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>July 4, 2023</study_first_submitted>
    <study_first_submitted_qc>July 24, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">July 27, 2023</study_first_posted>
    <last_update_submitted>July 24, 2023</last_update_submitted>
    <last_update_submitted_qc>July 24, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">July 27, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Beijing YouAn Hospital</investigator_affiliation>
      <investigator_full_name>LU JUN</investigator_full_name>
      <investigator_title>Chief physician</investigator_title>
    </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>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05962450
  org study id: Beijing YouAn Ethics [2023]060
  nct id: NCT05962450
  lead sponsor: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  The goal of this clinical trial is to explore the efficacy and safety of autologous iNKT
        cells in patients with progressed hepatocellular carcinoma (HCC) after treatment with PD-1
        antibody. The main question it aims to answer are:
  
          -  the efficacy of autologous iNKT cells in patients with progressed HCC after treatment
             with PD-1 antibody.
  
          -  the safety of autologous iNKT cells in patients with progressed HCC after treatment with
             PD-1 antibody.
  
        Participants will be randomized 1:1 to receive Regorafenib + PD-1 + iNKT cells (RPI group) or
        the treatment of Regorafenib + PD-1 (RP group).
  
        Researchers will compare RPI group and RP group to see whether the iNKT cells can achieve a
        better therapeutic effect on HCC patients with PD-1 resistance.
  Single center, randomized, open trial in Barcelona Clinic Liver Cancer（BCLC）C stage patients
        with progressed HCC after anti-angiogenic targeted drugs combined with PD-1 monoclonal
        antibody therapy to explore the efficacy and safety of autologous iNKT cells.
  
        This study includes screening period, treatment period and follow-up period (until the
        subjects withdrew their informed consent or received other anti-tumor therapy or participated
        in other clinical trials or the researchers judged that it is not in the best interests of
        patients to continue to participate in the study) after treatment.
  
        The patients will be randomized 1:1 using a random number table to receive Regorafenib + PD-1
        + iNKT cells (RPI group) or the treatment of Regorafenib + PD-1 (RP group).
  
          1. iNKT Cells：Intravenous infusion. The cells will be infused every two weeks as a course
             of treatment for up to six courses.
  
          2. PD-1：Intravenous infusion, according to the drug instructions.
  
          3. Regorafenib：Oral administration, according to the drug instructions. All target and
             non-target lesions will be assessed by chest, abdomen, and pelvis CT or MRI at baseline
             and every 8 weeks until radiological progression (according to mRECIST/iRECIST).
  
        Safety and side-effect profiles will be assessed based on the nature, frequency, and severity
        of adverse events, according to the National Cancer Institute (NCI) Common Terminology
        Criteria for Adverse Events (CTCAE), version 5.0.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  masking description: Block randomization was performed by the independent masked statistician. Two independent masked radiologist who are blinded to patients' clinical information will review the imaging examinations.
  measure: Progression-Free Survival (PFS)
  time frame: The time from enrollment to disease progression, or death from any cause, whichever occurred first, up to 24 months.
  description: The time from enrollment to disease progression according to the modified RECIST (mRECIST) guideline in trial immunotherapeutics, or death from any cause, whichever occurred first；the time from enrollment to confirmed disease progression (iCPD) according to the iRECIST
  measure: Disease control rate (DCR)
  time frame: Evaluation was performed every 8 weeks after the start of the treatment, up to 24 months.
  description: including complete response (CR), partial response (PR), and disease stabilization (SD), evaluated by imaging according to iRECIST for target lesions and assessed by MRI/CT.
  measure: Objective response rate (ORR)
  time frame: Evaluation was performed every 8 weeks after the start of the treatment, up to 24 months.
  description: complete response (CR) and partial response (PR) evaluated by imaging according to mRECIST/iRECIST for target lesions and assessed by MRI/CT.
  measure: Overall survival (OS)
  time frame: Time from the date of enrollment to the date of death from any cause, up to 36 months.
  description: Time from the date of enrollment to the date of death from any cause.
  measure: 1-year overall survival rate (1-year OS rate)
  time frame: Time from the date of enrollment to 1 year later.
  description: The proportion of subjects who were still alive from the date of enrollment to 1 year later
  measure: Duration of Overall Response (DOR)
  time frame: Time from the first tumor remission to the first recording of disease progression or death from any cause, up to 24 months..
  description: The time from the first tumor remission (CR or PR according to mRECIST/iRECIST) to the first recording of disease progression (PD according to mRECIST criteria or iCPD according to iRECIST) or death from any cause (whichever occurs first).
  measure: Time to progression (TTP)
  time frame: Time from the date of enrollment to the date of first disease progression, up to 24 months.
  description: Time from the date of enrollment to the date of first disease progression (PD) according to mRECIST or iCPD according to iRECIST).
  measure: Time to Quality of Life (QoL) Deterioration
  time frame: Time from the date of enrollment, up to 24 months.
  description: EORTC QLQ-C30: European Organization for Research on Treatment of Cancer Quality of Life Questionnare-Core 30.
  The totally 30 items spread out over five functional scales (15 items), three symptom scales (7 items), a global health status/QoL scale (2 items), and six single items. 1-28 item ranges 1: not at all, 2: a little, 3: quite a lit, 4: very much; 29-30 item ranges 1-7 from very poor to excellent. Raw score (RS) is an average of all items in each area. Standardized score is in the range of 0-100 by formula SS=[1-(RS-1)/n] x100 (function) or SS=[（RS-1）/n]x100 (symptom or overall health) respectively. A high scale score represents a higher/healthy response level.
  Time to deterioration was defined as a decrease from baseline of 10 points or more on the EORTC QLQ-C30 maintained for two consecutive assessments.
  arm group label: RPI group
  arm group type: Experimental
  description: Regorafenib + PD-1 + iNKT cells
  arm group label: RP group
  arm group type: Other
  description: Regorafenib + PD-1
  intervention type: Biological
  intervention name: iNKT Cells
  description: the iNKT cells will be intravenous infused every two weeks as a course of treatment for up to six courses , the reinfusion dose is determined according to the patient's body surface area, which was about 108~109cells/m2.
  arm group label: RPI group
  other name: Vα24+ T Cells
  intervention type: Drug
  intervention name: PD-1
  description: Intravenous infusion, according to the drug instructions.
  arm group label: RP group
  arm group label: RPI group
  intervention type: Drug
  intervention name: Regorafenib
  description: Oral administration, according to the drug instructions.
  arm group label: RP group
  arm group label: RPI group
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 75 Years
  healthy volunteers: No
  last name: Jun Lu, MD.
  role: Principal Investigator
  affiliation: Beijing YouAn Hospital
  last name: Jun Lu, MD.
  phone: 86-13661381489
  email: lujun98@ccmu.edu.cn
  last name: Songtao Liu, MD.
  phone: 86-13811120755
  email: botao8080@163.com
  facility: 
  country: China
  responsible party type: Principal Investigator
  investigator affiliation: Beijing YouAn Hospital
  investigator full name: LU JUN
  investigator title: Chief physician
  mesh term: Carcinoma
  mesh term: Carcinoma, Hepatocellular
  sharing ipd: No