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/NCT06013943</url>
    </required_header>
    <id_info>
      <org_study_id>EHBHKY2022-H040-P001</org_study_id>
      <nct_id>NCT06013943</nct_id>
    </id_info>
    <brief_title>Envafolimab Combined With GEMOX in First-line Treatment of Advanced GBC</brief_title>
    <official_title>Envafolimab Combined With GEMOX in First-line Treatment of Advanced Gallbladder Cancer : A Single Center, Single Arm, Phase II Trial</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Eastern Hepatobiliary Surgery Hospital</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Eastern Hepatobiliary Surgery 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>
        The TOPAZ-1 study compared the advantages and disadvantages of immune checkpoint inhibitor&#xD;
        anti-PD-L1 antibody combined with Gem/Cis chemotherapy (Gemcitabine and Cisplatin) and&#xD;
        Gem/Cis chemotherapy alone in first-line treatment of advanced biliary tract tumors (BTC,&#xD;
        which including gallbladder cancer). It was observed that chemotherapy combined with PD-L1&#xD;
        antibody improved progression-free survival (PFS) and overall survival (OS).&#xD;
  &#xD;
        As a standard first-line chemotherapy regimen for BTC too, Gemox chemotherapy (gemcitabine&#xD;
        and cisplatin) has a median OS of 9.5 months, and non-inferior survival time to Gem/Cis&#xD;
        chemotherapy. In addition, Gemox chemotherapy has been widely used in clinical practice&#xD;
        because it reduces the requirement on patients' renal function and has good tolerance.&#xD;
        Envafolimab is a novel fusion of humanized mono-domain PD-L1 antibody and human IgG Fc&#xD;
        fragment, which has shown good efficacy and safety in a variety of solid tumors. It is safe&#xD;
        and convenient to administer by subcutaneous injection. However, there is currently no&#xD;
        clinical data on Envafolimab combined with GEMOX chemotherapy in patients with advanced&#xD;
        gallbladder cancer (GBC).&#xD;
  &#xD;
        The goal of this clinical trial is to evaluate its efficacy and related safety in patients&#xD;
        with GBC. Eligible participants will receive Envafolimab (up to 12 months) plus gemcitabine&#xD;
        and cisplatin (up to 6-8 cycles) until progression of radiological disease, unacceptable&#xD;
        toxicity, or withdrawal from the study, whichever comes first.The primary endpoint was the&#xD;
        6-month PFS rate.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">March 17, 2023</start_date>
    <completion_date type="Anticipated">December 2025</completion_date>
    <primary_completion_date type="Anticipated">May 2025</primary_completion_date>
    <phase>Phase 2</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>6-month progression-free survival rate (PFS)</measure>
      <time_frame>6 months</time_frame>
      <description>Defined as the rate of patients had no disease progression or death (whichever occurred first) from the start of treatment to 6 months after treatment.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Progression free survival (PFS)</measure>
      <time_frame>Up to two years</time_frame>
      <description>Defined as the time from the start of treatment to the date of progressive disease, or death, whichever occurred first.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall survival (OS)</measure>
      <time_frame>Up to two years</time_frame>
      <description>Defined as the time from the start of treatment to the date of death from any cause.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Disease control rate (DCR) per RECIST 1.1</measure>
      <time_frame>Once every 3 weeks (±7 days) from the first day of Envafolimab treatment for a maximum of 2 years until confirmed objective disease progression, death, and study termination.</time_frame>
      <description>Defined as patients achieving a complete response [CR] or partial response [PR] or stable disease [SD].</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Objective response rate (ORR) per RECIST 1.1</measure>
      <time_frame>Once every 3 weeks (±7 days) from the first day of Envafolimab treatment for a maximum of 2 years until confirmed objective disease progression, death, and study termination.</time_frame>
      <description>Defined as patients achieving a complete response [CR] or partial response [PR].</description>
    </secondary_outcome>
    <other_outcome>
      <measure>Tumor markers</measure>
      <time_frame>Once every 9 weeks (±7 days) from the first day of Envafolimab treatment for a maximum of 2 years until confirmed objective disease progression, death, and study termination.</time_frame>
      <description>The peripheral blood samples of the patients were taken for the determination of tumor-associated Macrophages（TAMs）expression, and the results were analyzed to explore the effect of oxaliplatin on immune remodeling.</description>
    </other_outcome>
    <other_outcome>
      <measure>Lymphocyte count</measure>
      <time_frame>Once every 9 weeks (±7 days) from the first day of Envafolimab treatment for a maximum of 2 years until confirmed objective disease progression, death, and study termination.</time_frame>
      <description>Detecting the changes of lymphocyte count to conform the effect of oxaliplatin on tumor immune remodeling.</description>
    </other_outcome>
    <other_outcome>
      <measure>Adverse events</measure>
      <time_frame>Envafolimab treatment is performed once per cycle (±7 days), and the last one is completed within 30 days (±3 days) after ending treatment or before starting a new anti-tumor therapy.</time_frame>
      <description>Defined as the incidence of treatment emerge adverse events, treatment related adverse events and serious adverse events.</description>
    </other_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">30</enrollment>
    <condition>Gallbladder Cancer</condition>
    <arm_group>
      <arm_group_label>Envafolimab+Gemox</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Envafolimab+Gemox</intervention_name>
      <description>All of drugs were used for 6-8 cycles at the combined treatment stage, then Envafolimab and Gemcitabine continued at maintenance treatment stage until disease progression as defined by RECIST1.1, unacceptable toxicity, withdrawal from the study or death, or no more than 1 years.&#xD;
  Combined treatment stage: Envafolimab(150mg, iH, Q1W, Day1)+Gemcitabine(1000mg/m2, iv, Q3W, Day1 and Day8)+Cisplatin(1000mg/m2, iv, Q3W, Day1 and Day8);&#xD;
  Caintenance treatment stage: Envafolimab(400mg, iH, Day1, Q3W)+Gemcitabine(1000mg/m2, po, Day1-14, Q3W).</description>
      <arm_group_label>Envafolimab+Gemox</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Definite diagnosis of gallbladder carcinoma by histology or cytology；&#xD;
  &#xD;
            2. There is at least one measurable lesion (according to RECIST1.1);&#xD;
  &#xD;
            3. From 18 to 75 years old, ECOG physical strength score of 0-2;&#xD;
  &#xD;
            4. Basically normal bone marrow function: neutrophils &gt;1.5x10^9/L, platelets &gt;100x10^9/L;&#xD;
  &#xD;
            5. Adequate renal function: creatinine clearance &gt; 60ml/min;&#xD;
  &#xD;
            6. Adequate liver function: bilirubin ≤1.5ULN;&#xD;
  &#xD;
            7. No cardiac insufficiency or chest pain (medically uncontrollable); No myocardial&#xD;
               infarction in the 12 months prior to study initiation;&#xD;
  &#xD;
            8. Estimated survival time ≥3 months;&#xD;
  &#xD;
            9. The patient must sign an informed consent form.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Previous systematic therapy, including chemotherapy, immunotherapy and targeted&#xD;
               therapy;&#xD;
  &#xD;
            2. Secondary malignancies or other neoplasms (except superficial skin cancer and&#xD;
               localized low-grade malignancies) occurring in the 3 years prior to study initiation;&#xD;
  &#xD;
            3. The presence of brain or meningeal metastasis;&#xD;
  &#xD;
            4. Have active or previously recorded autoimmune or inflammatory diseases (eg Rheumatoid&#xD;
               arthritis, psoriasis, systemic lupus erythematosus, AIDS, etc. );&#xD;
  &#xD;
            5. Have received allogeneic organ transplantation (eg kidney transplantation, liver&#xD;
               transplantation, heart transplantation, etc. );&#xD;
  &#xD;
            6. Patients who need long-term oral hormone therapy due to their underlying diseases;&#xD;
  &#xD;
            7. Patients with interstitial pneumonia and autoimmune hepatitis;&#xD;
  &#xD;
            8. Inflammatory infections during the active period of infection or other patients who&#xD;
               may have disabilities receive planned treatment;&#xD;
  &#xD;
            9. Persons with a history of uncontrolled substance abuse or mental disorders;&#xD;
  &#xD;
           10. Patients with concomitant diseases that, in the judgment of the investigator, may&#xD;
               seriously endanger their own safety or may interfere with the completion of the study;&#xD;
  &#xD;
           11. Patients with poor renal function;&#xD;
  &#xD;
           12. Untreated complete/incomplete ileus that prevents eating or interferes with systemic&#xD;
               administration;&#xD;
  &#xD;
           13. Participated in other clinical trials;&#xD;
  &#xD;
           14. Pregnant and lactating women.&#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>Zhengang Yuan, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Eastern Hepatobiliary Surgery Hospital, Navy Medical University</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Zhengang Yuan, PhD</last_name>
      <phone>+86-021-81887453</phone>
      <email>yuanzg@163.com</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Peipei Shang, PhD</last_name>
      <phone>+86-021-81887453</phone>
      <email>peipei19850712@163.com</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Easter hepatobiliary surgery hospital</name>
        <address>
          <city>Shanghai</city>
          <state>Shanghai</state>
          <zip>200438</zip>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Zhengang Yuan, Ph.D</last_name>
        <phone>+86-021-81887453</phone>
        <email>yuanzg@163.com</email>
      </contact>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>April 12, 2023</study_first_submitted>
    <study_first_submitted_qc>August 25, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 28, 2023</study_first_posted>
    <last_update_submitted>September 14, 2023</last_update_submitted>
    <last_update_submitted_qc>September 14, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 15, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Eastern Hepatobiliary Surgery Hospital</investigator_affiliation>
      <investigator_full_name>Shen Feng</investigator_full_name>
      <investigator_title>Professor and Chief Surgeon</investigator_title>
    </responsible_party>
    <keyword>Envafolimab(immune checkpoint inhibitor anti-PD-L1 antibody)</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Gallbladder Neoplasms</mesh_term>
    </condition_browse>
    <!-- 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/NCT06013943
  org study id: EHBHKY2022-H040-P001
  nct id: NCT06013943
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  The TOPAZ-1 study compared the advantages and disadvantages of immune checkpoint inhibitor
        anti-PD-L1 antibody combined with Gem/Cis chemotherapy (Gemcitabine and Cisplatin) and
        Gem/Cis chemotherapy alone in first-line treatment of advanced biliary tract tumors (BTC,
        which including gallbladder cancer). It was observed that chemotherapy combined with PD-L1
        antibody improved progression-free survival (PFS) and overall survival (OS).
  
        As a standard first-line chemotherapy regimen for BTC too, Gemox chemotherapy (gemcitabine
        and cisplatin) has a median OS of 9.5 months, and non-inferior survival time to Gem/Cis
        chemotherapy. In addition, Gemox chemotherapy has been widely used in clinical practice
        because it reduces the requirement on patients' renal function and has good tolerance.
        Envafolimab is a novel fusion of humanized mono-domain PD-L1 antibody and human IgG Fc
        fragment, which has shown good efficacy and safety in a variety of solid tumors. It is safe
        and convenient to administer by subcutaneous injection. However, there is currently no
        clinical data on Envafolimab combined with GEMOX chemotherapy in patients with advanced
        gallbladder cancer (GBC).
  
        The goal of this clinical trial is to evaluate its efficacy and related safety in patients
        with GBC. Eligible participants will receive Envafolimab (up to 12 months) plus gemcitabine
        and cisplatin (up to 6-8 cycles) until progression of radiological disease, unacceptable
        toxicity, or withdrawal from the study, whichever comes first.The primary endpoint was the
        6-month PFS rate.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: 6-month progression-free survival rate (PFS)
  time frame: 6 months
  description: Defined as the rate of patients had no disease progression or death (whichever occurred first) from the start of treatment to 6 months after treatment.
  measure: Progression free survival (PFS)
  time frame: Up to two years
  description: Defined as the time from the start of treatment to the date of progressive disease, or death, whichever occurred first.
  measure: Overall survival (OS)
  time frame: Up to two years
  description: Defined as the time from the start of treatment to the date of death from any cause.
  measure: Disease control rate (DCR) per RECIST 1.1
  time frame: Once every 3 weeks (±7 days) from the first day of Envafolimab treatment for a maximum of 2 years until confirmed objective disease progression, death, and study termination.
  description: Defined as patients achieving a complete response [CR] or partial response [PR] or stable disease [SD].
  measure: Objective response rate (ORR) per RECIST 1.1
  time frame: Once every 3 weeks (±7 days) from the first day of Envafolimab treatment for a maximum of 2 years until confirmed objective disease progression, death, and study termination.
  description: Defined as patients achieving a complete response [CR] or partial response [PR].
  measure: Tumor markers
  time frame: Once every 9 weeks (±7 days) from the first day of Envafolimab treatment for a maximum of 2 years until confirmed objective disease progression, death, and study termination.
  description: The peripheral blood samples of the patients were taken for the determination of tumor-associated Macrophages（TAMs）expression, and the results were analyzed to explore the effect of oxaliplatin on immune remodeling.
  measure: Lymphocyte count
  time frame: Once every 9 weeks (±7 days) from the first day of Envafolimab treatment for a maximum of 2 years until confirmed objective disease progression, death, and study termination.
  description: Detecting the changes of lymphocyte count to conform the effect of oxaliplatin on tumor immune remodeling.
  measure: Adverse events
  time frame: Envafolimab treatment is performed once per cycle (±7 days), and the last one is completed within 30 days (±3 days) after ending treatment or before starting a new anti-tumor therapy.
  description: Defined as the incidence of treatment emerge adverse events, treatment related adverse events and serious adverse events.
  arm group label: Envafolimab+Gemox
  arm group type: Experimental
  intervention type: Drug
  intervention name: Envafolimab+Gemox
  description: All of drugs were used for 6-8 cycles at the combined treatment stage, then Envafolimab and Gemcitabine continued at maintenance treatment stage until disease progression as defined by RECIST1.1, unacceptable toxicity, withdrawal from the study or death, or no more than 1 years.
  Combined treatment stage: Envafolimab(150mg, iH, Q1W, Day1)+Gemcitabine(1000mg/m2, iv, Q3W, Day1 and Day8)+Cisplatin(1000mg/m2, iv, Q3W, Day1 and Day8);
  Caintenance treatment stage: Envafolimab(400mg, iH, Day1, Q3W)+Gemcitabine(1000mg/m2, po, Day1-14, Q3W).
  arm group label: Envafolimab+Gemox
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 75 Years
  healthy volunteers: No
  last name: Zhengang Yuan, PhD
  role: Principal Investigator
  affiliation: Eastern Hepatobiliary Surgery Hospital, Navy Medical University
  last name: Zhengang Yuan, PhD
  phone: +86-021-81887453
  email: yuanzg@163.com
  last name: Peipei Shang, PhD
  phone: +86-021-81887453
  email: peipei19850712@163.com
  facility: 
  status: Recruiting
  contact: 
  country: China
  responsible party type: Principal Investigator
  investigator affiliation: Eastern Hepatobiliary Surgery Hospital
  investigator full name: Shen Feng
  investigator title: Professor and Chief Surgeon
  mesh term: Gallbladder Neoplasms