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/NCT06033118</url>
    </required_header>
    <id_info>
      <org_study_id>cHCC-ICC</org_study_id>
      <nct_id>NCT06033118</nct_id>
    </id_info>
    <brief_title>Gemox Combined With Anlotinib and Sintilimab in Advanced cHCC-ICC</brief_title>
    <official_title>Gemox Combined With Anlotinib and Sintilimab in Advanced Combined Hepatocellular-cholangiocarcinoma: an Exploratory Study</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Sichuan University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Sichuan University</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 Purpose of This Study is to Evaluate the Efficacy and Safety of Gemox combined with&#xD;
        Anlotinib and Sintilimab as first-lineTherapy for Patients With advanced combined&#xD;
        hepatocellular-cholangiocarcinoma.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) accounts for 0.4%-14.2% of primary&#xD;
        hepatocellular carcinoma. As imaging and pathological diagnostic techniques for liver tumors&#xD;
        have improved, the detection rate of cHCC-CCA puncture biopsies and surgical procedures has&#xD;
        increased. Oxaliplatin-containing chemotherapy was previously recommended for the treatment&#xD;
        of advanced cHCC-ICC, but its efficacy was not satisfactory. Targeted therapy and&#xD;
        immunotherapy have made breakthroughs in both advanced HCC and CCA, providing a new direction&#xD;
        for exploration in the treatment of advanced cHCC-CCA. Currently, targeted combination&#xD;
        immunotherapy has become the preferred first-line treatment strategy for advanced HCC.&#xD;
        Chemotherapy combined with immunotherapy is also the preferred first-line treatment option&#xD;
        for advanced CCA. To balance the treatment of HCC and ICC, this study further investigates&#xD;
        the efficacy and safety of Gemox chemotherapy combined with anlotinib and&#xD;
        Sintilimab(anti-PD-1 monoclonal antibody) immunotherapy in advanced cHCC-ICC, to provide a&#xD;
        new treatment strategy and reference for the clinical treatment of advanced cHCC-CCA&#xD;
        patients.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 1, 2023</start_date>
    <completion_date type="Anticipated">August 1, 2026</completion_date>
    <primary_completion_date type="Anticipated">July 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>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>ORR</measure>
      <time_frame>Every 2 cycles (each cycle is 21 days)starting from the first cycle, and every 3 cycles after 6 cycles</time_frame>
      <description>Objective Response Rate according to Response Evaluation Criteria in Solid Tumors (RECIST) version. 1.1</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Safety and tolerability</measure>
      <time_frame>3 months after the last administration of drugs</time_frame>
      <description>Incidence of Treatment-Emergent Adverse Events,Version 5.0 and AEs leading to dose interruption or discontinuation.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>PFS</measure>
      <time_frame>Every 2 cycles(each cycle is 21 days) starting from the first cycle, and every 3 cycles after 6 cycles</time_frame>
      <description>Progression-free survival is determined from the date of treatment to PD or death from any cause</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>OS</measure>
      <time_frame>Every 2 cycles(each cycle is 21 days) starting from the first cycle, and every 3 cycles after 6 cycles</time_frame>
      <description>OS is the time interval from the start of treatment to death due to any reason or lost of follow-up</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">25</enrollment>
    <condition>Combined Hepatocellular Cholangiocarcinoma</condition>
    <arm_group>
      <arm_group_label>Gemox combined with Anlotinib and Sintilimab</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Gemox chemotherapy（gemcitabine 1g/m2 ivgtt d1,d8 +oxaliplatin 85g/m2 ivgtt d1，q3w，anlotinib (8mg po d1-14 q3w )and Sintilimab (200mg ivgtt d1 q3w)</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>gemcitabine ,oxaliplatin,anlotinib,Sintilimab</intervention_name>
      <description>Gemox chemotherapy（gemcitabine 1g/m2 ivgtt d1,d8 +oxaliplatin 85g/m2 ivgtt d1，q3w，anlotinib (8mg po d1-14 q3w )and Sintilimab (200mg ivgtt d1 q3w)</description>
      <arm_group_label>Gemox combined with Anlotinib and Sintilimab</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. .Age 18-75 years;&#xD;
  &#xD;
            2. .Histologically or cytologically confirmed diagnosis of aCombined&#xD;
               hepatocellular-cholangiocarcinoma;&#xD;
  &#xD;
            3. .Non resectable or metastatic cHCC-ICC patients who have not received systemic&#xD;
               treatment or first-line treatment progress (only non arotinib Targeted therapy or non&#xD;
               GEMOX chemotherapy) in the past, and have at least one measurable lesion (RECIST&#xD;
               v1.1);&#xD;
  &#xD;
            4. .Life expectancy ≥ 3 months;&#xD;
  &#xD;
            5. .ECOG PS 0-1;&#xD;
  &#xD;
            6. .Child Pugh A/B ≤ 7;&#xD;
  &#xD;
            7. .Adequate organ function including the following:Total bilirubin ≤1.5 times upper&#xD;
               limit of normal (ULN),Aspartate transaminase (AST) and alanine transaminase (ALT)&#xD;
               ≤3×ULN,Alkaline phosphatase≤2.5×ULN (If the tumor invaded the liver, ≤3×ULN), Serum&#xD;
               creatinine≤1.5×ULN,Serum amylase and lipase≤1.5×ULN,International standardized ratio&#xD;
               (INR)/partial prothrombin time (PTT)≤1.5×ULN;Platelet count ≥ 75,000 /mm3.Hemoglobin&#xD;
               (Hb) ≥ 9 g/dL.Absolute neutrophil count (ANC) ≥ 1500/mm3.&#xD;
  &#xD;
            8. .Strict contraception.&#xD;
  &#xD;
            9. .Patients must be able to understand and be willing to sign the written informed&#xD;
               consent form. A signed informed consent form must be appropriately obtained prior to&#xD;
               the conduct of any trial-specific procedure.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Has a history of severe allergic reactions to chimeric, human or humanized antibodies,&#xD;
               or fusion proteins.&#xD;
  &#xD;
            2. Pregnant or lactating women, men and women of childbearing age who are unwilling or&#xD;
               unable to take effective contraceptive measures;&#xD;
  &#xD;
            3. History of other malignant tumors in the past 5 years, except for malignant tumors&#xD;
               that have received treatment for the purpose of cure, and have no known active&#xD;
               diseases for ≥ 5 years before the first administration, and have a low potential risk&#xD;
               of recurrence; Fully treated non Melanoma skin cancer or malignant lentigo without&#xD;
               disease evidence; Fully treated Carcinoma in situ, no disease evidence;&#xD;
  &#xD;
            4. Moderate or higher amounts of pleural and ascitic fluid with clinical symptoms;&#xD;
  &#xD;
            5. Active bleeding or abnormal coagulation function (PT&gt;16s, APTT&gt;43s, INR&gt;1.5) × ULN),&#xD;
               with a tendency to bleed or undergoing thrombolysis, anticoagulation, or antiplatelet&#xD;
               therapy;&#xD;
  &#xD;
            6. Hepatic encephalopathy;&#xD;
  &#xD;
            7. Within the past 6 months, there has been a history of gastrointestinal bleeding or a&#xD;
               clear tendency for gastrointestinal bleeding, such as known local active ulcer&#xD;
               lesions, fecal occult blood+or above, which cannot be included in the group; If there&#xD;
               is continuous fecal occult blood, gastroscopy should be performed;&#xD;
  &#xD;
            8. Patients with severe gastroesophageal varices who require interventional treatment;&#xD;
  &#xD;
            9. Untreated active hepatitis B. (Note: Hepatitis B patients who receive antiviral&#xD;
               treatment and whose HBV Viral load is less than 2000IU/ml can be allowed to&#xD;
               participate in the study)&#xD;
  &#xD;
           10. Active hepatitis C, that is, those who are anti-HCV positive or HCV-RNA positive and&#xD;
               have abnormal liver function;&#xD;
  &#xD;
           11. Having a history of psychotropic substance abuse, unable to quit, or having a history&#xD;
               of mental disorders;&#xD;
  &#xD;
           12. Patients who received solid organ transplantation or bone marrow transplantation, or&#xD;
               had active autoimmune diseases requiring systemic Sex therapy within 2 years before&#xD;
               the first administration;&#xD;
  &#xD;
           13. Existence of immune deficiency diseases or HIV infection;&#xD;
  &#xD;
           14. There has been objective evidence that Pulmonary fibrosis, interstitial pneumonia,&#xD;
               pneumoconiosis, radiation pneumonia, drug-related pneumonia and serious impairment of&#xD;
               lung function exist in the past or at present;&#xD;
  &#xD;
           15. Major surgery on the liver or other parts has been performed within 4 weeks before the&#xD;
               first administration, or minor surgery (such as simple resection, tooth extraction,&#xD;
               etc.) has been performed within 1 week before the first administration;&#xD;
  &#xD;
           16. Received the vaccine within 30 days before the first administration;&#xD;
  &#xD;
           17. Abdominal fistula, gastrointestinal perforation, or abdominal abscess occurred within&#xD;
               4 weeks prior to the first administration;&#xD;
  &#xD;
           18. For any significant clinical and laboratory abnormalities, the researchers believe&#xD;
               that they will affect the safety evaluators, such as: active infection requiring&#xD;
               systemic Sex therapy, uncontrollable diabetes, hypertension patients who cannot fall&#xD;
               to the normal range (systolic pressure&gt;140mmHg, diastolic pressure&gt;90mmHg), myocardial&#xD;
               infarction within 6 months, thyroid dysfunction (&gt;NCI CTCAE v4.0 Level 1 standard)&#xD;
               after treatment with two or less antihypertensive drugs;&#xD;
  &#xD;
           19. Researchers believe that it is not suitable for inclusion in the study.&#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_contact>
      <last_name>Yu Yang, M.D</last_name>
      <phone>18980606616</phone>
      <email>yangyuflying@hotmail.com</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Qiuji Wu, M.D</last_name>
      <phone>18380325408</phone>
      <email>anyandywqj@163.com</email>
    </overall_contact_backup>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>July 10, 2023</study_first_submitted>
    <study_first_submitted_qc>September 10, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 13, 2023</study_first_posted>
    <last_update_submitted>September 10, 2023</last_update_submitted>
    <last_update_submitted_qc>September 10, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 13, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Sichuan University</investigator_affiliation>
      <investigator_full_name>Zhen-Yu Ding</investigator_full_name>
      <investigator_title>Director</investigator_title>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Cholangiocarcinoma</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Gemcitabine</mesh_term>
      <mesh_term>Oxaliplatin</mesh_term>
    </intervention_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/NCT06033118
  org study id: cHCC-ICC
  nct id: NCT06033118
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  The Purpose of This Study is to Evaluate the Efficacy and Safety of Gemox combined with
        Anlotinib and Sintilimab as first-lineTherapy for Patients With advanced combined
        hepatocellular-cholangiocarcinoma.
  Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) accounts for 0.4%-14.2% of primary
        hepatocellular carcinoma. As imaging and pathological diagnostic techniques for liver tumors
        have improved, the detection rate of cHCC-CCA puncture biopsies and surgical procedures has
        increased. Oxaliplatin-containing chemotherapy was previously recommended for the treatment
        of advanced cHCC-ICC, but its efficacy was not satisfactory. Targeted therapy and
        immunotherapy have made breakthroughs in both advanced HCC and CCA, providing a new direction
        for exploration in the treatment of advanced cHCC-CCA. Currently, targeted combination
        immunotherapy has become the preferred first-line treatment strategy for advanced HCC.
        Chemotherapy combined with immunotherapy is also the preferred first-line treatment option
        for advanced CCA. To balance the treatment of HCC and ICC, this study further investigates
        the efficacy and safety of Gemox chemotherapy combined with anlotinib and
        Sintilimab(anti-PD-1 monoclonal antibody) immunotherapy in advanced cHCC-ICC, to provide a
        new treatment strategy and reference for the clinical treatment of advanced cHCC-CCA
        patients.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: ORR
  time frame: Every 2 cycles (each cycle is 21 days)starting from the first cycle, and every 3 cycles after 6 cycles
  description: Objective Response Rate according to Response Evaluation Criteria in Solid Tumors (RECIST) version. 1.1
  measure: Safety and tolerability
  time frame: 3 months after the last administration of drugs
  description: Incidence of Treatment-Emergent Adverse Events,Version 5.0 and AEs leading to dose interruption or discontinuation.
  measure: PFS
  time frame: Every 2 cycles(each cycle is 21 days) starting from the first cycle, and every 3 cycles after 6 cycles
  description: Progression-free survival is determined from the date of treatment to PD or death from any cause
  measure: OS
  time frame: Every 2 cycles(each cycle is 21 days) starting from the first cycle, and every 3 cycles after 6 cycles
  description: OS is the time interval from the start of treatment to death due to any reason or lost of follow-up
  arm group label: Gemox combined with Anlotinib and Sintilimab
  arm group type: Experimental
  description: Gemox chemotherapy（gemcitabine 1g/m2 ivgtt d1,d8 +oxaliplatin 85g/m2 ivgtt d1，q3w，anlotinib (8mg po d1-14 q3w )and Sintilimab (200mg ivgtt d1 q3w)
  intervention type: Drug
  intervention name: gemcitabine ,oxaliplatin,anlotinib,Sintilimab
  description: Gemox chemotherapy（gemcitabine 1g/m2 ivgtt d1,d8 +oxaliplatin 85g/m2 ivgtt d1，q3w，anlotinib (8mg po d1-14 q3w )and Sintilimab (200mg ivgtt d1 q3w)
  arm group label: Gemox combined with Anlotinib and Sintilimab
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 75 Years
  healthy volunteers: No
  last name: Yu Yang, M.D
  phone: 18980606616
  email: yangyuflying@hotmail.com
  last name: Qiuji Wu, M.D
  phone: 18380325408
  email: anyandywqj@163.com
  responsible party type: Principal Investigator
  investigator affiliation: Sichuan University
  investigator full name: Zhen-Yu Ding
  investigator title: Director
  mesh term: Cholangiocarcinoma
  mesh term: Gemcitabine
  mesh term: Oxaliplatin