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/NCT06006390</url>
    </required_header>
    <id_info>
      <org_study_id>PBC058</org_study_id>
      <nct_id>NCT06006390</nct_id>
    </id_info>
    <brief_title>CEA Targeting Chimeric Antigen Receptor T Lymphocytes (CAR-T) in the Treatment of CEA Positive Advanced Solid Tumors</brief_title>
    <official_title>Chimeric Antigen Receptor T Lymphocytes (CAR-T) Targeting CEA in the Treatment of CEA Positive Clinical Study of Advanced Malignant Solid Tumors</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Chongqing Precision Biotech Co., Ltd</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Shanxi Bethune Hospital</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Chongqing Precision Biotech Co., Ltd</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 is a single-arm, open-label, dose-escalating + dose-expansion clinical study,&#xD;
        aiming to evaluate the safety and efficacy of CEA-targeted CAR-T cell preparations, and to&#xD;
        preliminarily observe the study drug in CEA-positive advanced malignant tumors. The&#xD;
        pharmacokinetic characteristics of CAR-T cell preparations for the treatment of patients with&#xD;
        CEA-positive advanced malignancies were obtained and the recommended dose and infusion&#xD;
        schedule.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        According to the different infusion methods, it is divided into two subgroups: intravenous&#xD;
        infusion and local infusion through the peritoneal cavity. Each subgroup includes a dose&#xD;
        exploration stage (Part A) and a dose expansion stage (Part B). 3 patients were explored,&#xD;
        starting from the low-dose group, and in the dose expansion phase, the safety and efficacy&#xD;
        were further verified according to the safe recommended dose obtained in the dose exploration&#xD;
        phase.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Anticipated">August 31, 2023</start_date>
    <completion_date type="Anticipated">August 31, 2026</completion_date>
    <primary_completion_date type="Anticipated">December 31, 2025</primary_completion_date>
    <phase>Phase 1/Phase 2</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Non-Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>To evaluate the safety of CAR-T cell preparations in the treatment of CEA-positive advanced malignancies [Safety and Tolerability]</measure>
      <time_frame>1 month</time_frame>
      <description>The incidence of adverse events after CEA CAR-T cell infusion was assessed by the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, version 5.0)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Obtained the recommended dose and infusion regimen of CAR-T cells for the treatment of patients with CEA-positive advanced malignancies[Safety and Tolerability]</measure>
      <time_frame>28 days</time_frame>
      <description>Dose-limiting toxicity after CEA CAR-T cell infusion</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Assessing disease control rates of CAR-T cell preparations in CEA-positive advanced malignancies[Effectiveness]</measure>
      <time_frame>3 months</time_frame>
      <description>Disease control rate: The proportion of subjects who achieved CR, PR, SD after CAR-T infusion accounted for all treated subjects (Assessed based on RECIST criteria)，the minimum value is 0%，maximum value is 100%, and higher scores mean a better outcome.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>AUCS of CEA CAR-T cells [Cell dynamics]</measure>
      <time_frame>3 months</time_frame>
      <description>AUCS is defined as the area under the curve in 90 days</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>CMAX of CEA CAR-T cells [Cell dynamics]</measure>
      <time_frame>3 months</time_frame>
      <description>CMAX is defined as the highest concentration of CEA CAR-T cells expanded in peripheral blood</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>TMAX of CEA CAR-T cells[Cell dynamics]</measure>
      <time_frame>3 months</time_frame>
      <description>TMAX is defined as the time to reach the highest concentration</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Pharmacodynamics of CEA CAR-T cells[Cell dynamics]</measure>
      <time_frame>3 months</time_frame>
      <description>The content of CEA in peripheral blood was detected by ELISA at the visit points specified in the research protocol</description>
    </secondary_outcome>
    <other_outcome>
      <measure>Objective response rate (ORR) of CEA CAR-T treatment in patients with CEA-positive advanced malignancies[Effectiveness]</measure>
      <time_frame>2 years</time_frame>
      <description>Objective response rate includes：The proportion of subjects who achieved CR, PR after CAR-T infusion accounted for all treated subjects (Assessed based on RECIST criteria)，the minimum value is 0%，maximum value is 100%, and higher scores mean a better outcome.</description>
    </other_outcome>
    <other_outcome>
      <measure>Duration of Response (DOR) of CEA CAR-T treatment in patients with CEA-positive advanced malignancies[Effectiveness]</measure>
      <time_frame>2 years</time_frame>
      <description>DOR will be assessed from the first assessment of CR/PR/SD to the first assessment of recurrence or progression of the disease or death from any cause</description>
    </other_outcome>
    <other_outcome>
      <measure>Progress-free survival(PFS) of CEA CAR-T treatment in patients with CEA-positive advanced malignancies[Effectiveness]</measure>
      <time_frame>2 years</time_frame>
      <description>PFS will be assessed from the first CEA-CAR-T cell infusion to death from any cause or the first assessment of progression(Assessed based on RECIST criteria)</description>
    </other_outcome>
    <other_outcome>
      <measure>Overall survival(OS)of CEA CAR-T treatment in patients with CEA-positive advanced malignancies[Effectiveness]</measure>
      <time_frame>2 years</time_frame>
      <description>OS will be assessed from the first CEA-CAR-T cell infusion to death from any cause (Assessed by investigators based on IRECIST criteria)</description>
    </other_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">60</enrollment>
    <condition>Gastric Cancer</condition>
    <condition>Colon Cancer</condition>
    <condition>Rectal Cancer</condition>
    <condition>Esophageal Cancer</condition>
    <condition>Pancreas Cancer</condition>
    <condition>Lung Cancer</condition>
    <condition>Breast Cancer</condition>
    <arm_group>
      <arm_group_label>Intravenous of CD70-targeted CAR-T</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Infusion of CEA-targeted CAR-T cells by dose of 3-10x10^6 cells/kg</description>
    </arm_group>
    <arm_group>
      <arm_group_label>intraperitoneal injection of CD70-targeted CAR-T</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Infusion of CEA-targeted CAR-T cells by dose of 1-10x10^6 cells/kg</description>
    </arm_group>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>CEA-targeted CAR-T cells</intervention_name>
      <description>Administration method: intravenous infusion； Subjects will receive conditioning therapy by Fludarabine and Cyclophosphamide before cell infusion.</description>
      <arm_group_label>Intravenous of CD70-targeted CAR-T</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>CEA-targeted CAR-T cells</intervention_name>
      <description>Administration method: intraperitoneal injection；Subjects will receive conditioning therapy by Fludarabine and Cyclophosphamide before cell infusion.</description>
      <arm_group_label>intraperitoneal injection of CD70-targeted CAR-T</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Age ≥18 years old, male or female;&#xD;
  &#xD;
            2. Advanced, metastatic or recurrent malignant tumors diagnosed by histology or&#xD;
               pathology, mainly colorectal cancer, esophageal cancer, gastric cancer, and pancreatic&#xD;
               cancer;&#xD;
  &#xD;
            3. After receiving at least second-line standard treatment failure (disease progression&#xD;
               or intolerance, such as surgery, chemotherapy, radiotherapy, etc.) or lack of&#xD;
               effective treatment methods;&#xD;
  &#xD;
            4. Immunohistochemical staining of tumor samples within 3 months confirmed that the tumor&#xD;
               was CEA positive (clear membrane staining, positive rate ≥ 10%); , the positive rate ≥&#xD;
               10%), the serum CEA of the patient is required to exceed 10ug/L.&#xD;
  &#xD;
            5. At least one assessable lesion according to RECIST 1.1 criteria;&#xD;
  &#xD;
            6. ECOG score 0-2 points;&#xD;
  &#xD;
            7. No serious mental disorder;&#xD;
  &#xD;
            8. Unless otherwise specified, the function of the vital organs of the subject shall meet&#xD;
               the following conditions:&#xD;
  &#xD;
                 1. Blood routine: white blood cells&gt;3.0×10^9/L, neutrophils&gt;0.8×10^9/L, lymphocytes&#xD;
                    cells&gt;0.5×10^9/L, platelets&gt;75×10^9/L, hemoglobin&gt;80g/L;&#xD;
  &#xD;
                 2. Cardiac function: echocardiography showed cardiac ejection fraction ≥50%, and no&#xD;
                    obvious abnormality was found on electrocardiogram;&#xD;
  &#xD;
                 3. Renal function: serum creatinine≤2.0×ULN;&#xD;
  &#xD;
                 4. Liver function: ALT and AST ≤3.0×ULN (for patients with liver tumor infiltration,&#xD;
                    it can be relaxed to ≤5.0×ULN);&#xD;
  &#xD;
                 5. Total bilirubin≤3.0×ULN;&#xD;
  &#xD;
                 6. Oxygen saturation ≥95% in non-oxygen state.&#xD;
  &#xD;
            9. Have apheresis or venous blood collection standards, and have no other&#xD;
               contraindications for cell collection;&#xD;
  &#xD;
           10. Subjects agree to use reliable and effective contraceptive methods for contraception&#xD;
               within 1 year after signing the informed consent form to receiving CAR-T cell infusion&#xD;
               (excluding rhythm contraception);&#xD;
  &#xD;
           11. The patients themselves or their guardians agree to participate in this clinical trial&#xD;
               and sign the ICF, indicating that they understand the purpose and procedures of this&#xD;
               clinical trial and are willing to participate in the research.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Those who have central nervous system metastasis or meningeal metastasis at the time&#xD;
               of screening are judged by the investigator to be unsuitable for inclusion;&#xD;
  &#xD;
            2. Participated in other clinical studies within 1 month before screening;&#xD;
  &#xD;
            3. vaccinated with live attenuated vaccine within 4 weeks before screening;&#xD;
  &#xD;
            4. Received the following anti-tumor treatments before screening: Received chemotherapy,&#xD;
               targeted therapy or other experimental drug treatments within 14 days or at least 5&#xD;
               half-lives (whichever is shorter);&#xD;
  &#xD;
            5. Active infection or uncontrollable infection requiring systemic treatment;&#xD;
  &#xD;
            6. Patients with intestinal obstruction, active gastrointestinal bleeding, or a history&#xD;
               of gastrointestinal bleeding within 3 months;&#xD;
  &#xD;
            7. Except for alopecia or peripheral neuropathy, the toxicity of previous anti-tumor&#xD;
               therapy has not improved to the baseline level or ≤ grade 1;&#xD;
  &#xD;
            8. Suffering from any of the following heart diseases:&#xD;
  &#xD;
                 1. New York Heart Association (NYHA) stage III or IV congestive heart failure;&#xD;
  &#xD;
                 2. Myocardial infarction or coronary artery bypass grafting (CABG) within 6 months&#xD;
                    before enrollment;&#xD;
  &#xD;
                 3. Clinically significant ventricular arrhythmia, or a history of unexplained&#xD;
                    syncope (except those caused by vasovagal or dehydration);&#xD;
  &#xD;
                 4. History of severe non-ischemic cardiomyopathy;&#xD;
  &#xD;
            9. Patients with active autoimmune disease, or other patients requiring long-term&#xD;
               immunosuppressive therapy;&#xD;
  &#xD;
           10. Suffering from other uncured malignant tumors in the past 3 years or at the same time,&#xD;
               except cervical carcinoma in situ and basal cell carcinoma of the skin;&#xD;
  &#xD;
           11. Hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) positive and&#xD;
               peripheral blood hepatitis B virus (HBV) DNA titer test is greater than the normal&#xD;
               range; hepatitis C virus (HCV) antibody positive and peripheral blood hepatitis C&#xD;
               Virus (HCV) RNA test is greater than the normal range; human immunodeficiency virus&#xD;
               (HIV) antibody positive; syphilis test positive;&#xD;
  &#xD;
           12. Women who are pregnant or breastfeeding;&#xD;
  &#xD;
           13. Other investigators deem it unsuitable to participate in the research.&#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>Qi Mei, M.D</last_name>
      <role>Principal Investigator</role>
      <affiliation>Shanxi Bethune Hospital</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Shuang Wei, M.D</last_name>
      <role>Principal Investigator</role>
      <affiliation>Shanxi Bethune Hospital</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Qi Mei, M.D</last_name>
      <phone>15871708675</phone>
      <email>borismq@hotmail.com</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Shuang Wei, M.D</last_name>
      <phone>18062087116</phone>
      <email>wsdavid2001@163.com</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Shanxi Bethune Hospital</name>
        <address>
          <city>Taiyuan</city>
          <state>Shanxi</state>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Qi Mei, MD</last_name>
        <phone>15871708675</phone>
        <email>borismq@hotmail.com</email>
      </contact>
    </location>
    <location>
      <facility>
        <name>Shanxi Bethune Hospital</name>
        <address>
          <city>Taiyuan</city>
          <state>Shanxi</state>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Shuang Wei, MD</last_name>
        <phone>18062087116</phone>
        <email>wsdavid2001@163.com</email>
      </contact>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 17, 2023</study_first_submitted>
    <study_first_submitted_qc>August 17, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 23, 2023</study_first_posted>
    <last_update_submitted>August 24, 2023</last_update_submitted>
    <last_update_submitted_qc>August 24, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 25, 2023</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>Pancreatic Neoplasms</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/NCT06006390
  org study id: PBC058
  nct id: NCT06006390
  lead sponsor: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  This study is a single-arm, open-label, dose-escalating + dose-expansion clinical study,
        aiming to evaluate the safety and efficacy of CEA-targeted CAR-T cell preparations, and to
        preliminarily observe the study drug in CEA-positive advanced malignant tumors. The
        pharmacokinetic characteristics of CAR-T cell preparations for the treatment of patients with
        CEA-positive advanced malignancies were obtained and the recommended dose and infusion
        schedule.
  According to the different infusion methods, it is divided into two subgroups: intravenous
        infusion and local infusion through the peritoneal cavity. Each subgroup includes a dose
        exploration stage (Part A) and a dose expansion stage (Part B). 3 patients were explored,
        starting from the low-dose group, and in the dose expansion phase, the safety and efficacy
        were further verified according to the safe recommended dose obtained in the dose exploration
        phase.
  allocation: Non-Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: To evaluate the safety of CAR-T cell preparations in the treatment of CEA-positive advanced malignancies [Safety and Tolerability]
  time frame: 1 month
  description: The incidence of adverse events after CEA CAR-T cell infusion was assessed by the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, version 5.0)
  measure: Obtained the recommended dose and infusion regimen of CAR-T cells for the treatment of patients with CEA-positive advanced malignancies[Safety and Tolerability]
  time frame: 28 days
  description: Dose-limiting toxicity after CEA CAR-T cell infusion
  measure: Assessing disease control rates of CAR-T cell preparations in CEA-positive advanced malignancies[Effectiveness]
  time frame: 3 months
  description: Disease control rate: The proportion of subjects who achieved CR, PR, SD after CAR-T infusion accounted for all treated subjects (Assessed based on RECIST criteria)，the minimum value is 0%，maximum value is 100%, and higher scores mean a better outcome.
  measure: AUCS of CEA CAR-T cells [Cell dynamics]
  time frame: 3 months
  description: AUCS is defined as the area under the curve in 90 days
  measure: CMAX of CEA CAR-T cells [Cell dynamics]
  time frame: 3 months
  description: CMAX is defined as the highest concentration of CEA CAR-T cells expanded in peripheral blood
  measure: TMAX of CEA CAR-T cells[Cell dynamics]
  time frame: 3 months
  description: TMAX is defined as the time to reach the highest concentration
  measure: Pharmacodynamics of CEA CAR-T cells[Cell dynamics]
  time frame: 3 months
  description: The content of CEA in peripheral blood was detected by ELISA at the visit points specified in the research protocol
  measure: Objective response rate (ORR) of CEA CAR-T treatment in patients with CEA-positive advanced malignancies[Effectiveness]
  time frame: 2 years
  description: Objective response rate includes：The proportion of subjects who achieved CR, PR after CAR-T infusion accounted for all treated subjects (Assessed based on RECIST criteria)，the minimum value is 0%，maximum value is 100%, and higher scores mean a better outcome.
  measure: Duration of Response (DOR) of CEA CAR-T treatment in patients with CEA-positive advanced malignancies[Effectiveness]
  time frame: 2 years
  description: DOR will be assessed from the first assessment of CR/PR/SD to the first assessment of recurrence or progression of the disease or death from any cause
  measure: Progress-free survival(PFS) of CEA CAR-T treatment in patients with CEA-positive advanced malignancies[Effectiveness]
  time frame: 2 years
  description: PFS will be assessed from the first CEA-CAR-T cell infusion to death from any cause or the first assessment of progression(Assessed based on RECIST criteria)
  measure: Overall survival(OS)of CEA CAR-T treatment in patients with CEA-positive advanced malignancies[Effectiveness]
  time frame: 2 years
  description: OS will be assessed from the first CEA-CAR-T cell infusion to death from any cause (Assessed by investigators based on IRECIST criteria)
  arm group label: Intravenous of CD70-targeted CAR-T
  arm group type: Experimental
  description: Infusion of CEA-targeted CAR-T cells by dose of 3-10x10^6 cells/kg
  arm group label: intraperitoneal injection of CD70-targeted CAR-T
  arm group type: Experimental
  description: Infusion of CEA-targeted CAR-T cells by dose of 1-10x10^6 cells/kg
  intervention type: Biological
  intervention name: CEA-targeted CAR-T cells
  description: Administration method: intravenous infusion； Subjects will receive conditioning therapy by Fludarabine and Cyclophosphamide before cell infusion.
  arm group label: Intravenous of CD70-targeted CAR-T
  intervention type: Biological
  intervention name: CEA-targeted CAR-T cells
  description: Administration method: intraperitoneal injection；Subjects will receive conditioning therapy by Fludarabine and Cyclophosphamide before cell infusion.
  arm group label: intraperitoneal injection of CD70-targeted CAR-T
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Qi Mei, M.D
  role: Principal Investigator
  affiliation: Shanxi Bethune Hospital
  last name: Shuang Wei, M.D
  role: Principal Investigator
  affiliation: Shanxi Bethune Hospital
  last name: Qi Mei, M.D
  phone: 15871708675
  email: borismq@hotmail.com
  last name: Shuang Wei, M.D
  phone: 18062087116
  email: wsdavid2001@163.com
  facility: 
  status: Recruiting
  contact: 
  facility: 
  status: Recruiting
  contact: 
  country: China
  responsible party type: Sponsor
  mesh term: Pancreatic Neoplasms
  sharing ipd: No