<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/NCT04454905</url>
  </required_header>
  <id_info>
    <org_study_id>B2020-098-01</org_study_id>
    <nct_id>NCT04454905</nct_id>
  </id_info>
  <brief_title>Camrelizumab in Combination With Apatinib in Advanced ICC: A Single-arm Phase II Study</brief_title>
  <official_title>A Single-arm Phase II Study to Evaluate Camrelizumab in Combination With Apatinib in Patients With Advanced Intrahepatic Cholangiocarcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sun Yat-sen University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Jiangsu HengRui Medicine Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Sun Yat-sen 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>
      This is a single arm, open-label, non-randomized and single-center phase II clinical study,&#xD;
      to evaluate the safety, tolerance, and efficacy of Camrelizumab in combination with Apatinib&#xD;
      in patients with advanced intrahepatic cholangiocarcinoma (ICC).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      It is estimated that 50 patients who met the study criteria will be enrolled in 3 years and&#xD;
      treated with Camrelizumab plus Apatinib in SYSUCC. The investigators will follow up and&#xD;
      collect subjects' data to evaluate the efficacy and safety of treatment, including objective&#xD;
      response rate (ORR) and Progression-free Survival (PFS) and Overall Survival (OS), until&#xD;
      disease progression or death. Histopathology and multi-omics data analysis will be used to&#xD;
      explore potential biomarkers of treatment response.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">August 1, 2020</start_date>
  <completion_date type="Anticipated">July 1, 2025</completion_date>
  <primary_completion_date type="Anticipated">July 1, 2024</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>Progression-free Survival (PFS)</measure>
    <time_frame>Three years</time_frame>
    <description>A duration from the date of initial treatment to disease progression (defined by RECIST 1.1) or death of any cause.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate (ORR)</measure>
    <time_frame>Three years</time_frame>
    <description>Proportion of patients whose tumor volume has reached a predetermined value and can maintain a minimum time limit, including complete response and partial response patients.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>Three years</time_frame>
    <description>Duration from the date of initial treatment to the date of death due to any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease Control Rate (DCR)</measure>
    <time_frame>Two years</time_frame>
    <description>Proportion of patients whose tumor volume control (reduced or enlarged) reaches a predetermined value and can maintain a minimum time limit.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response (DoR)</measure>
    <time_frame>Two years</time_frame>
    <description>Duration from the first time reported partial response or complete response to the first time of disease progression or death.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Progression (TTP)</measure>
    <time_frame>Two years</time_frame>
    <description>A duration from the date of initial treatment to disease progression (defined by RECIST 1.1)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events (AE)</measure>
    <time_frame>Two years</time_frame>
    <description>Any adverse events related with treatment drugs and details include adverse events type, frequency and severity.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Intrahepatic Cholangiocarcinoma</condition>
  <arm_group>
    <arm_group_label>Camrelizumab combination with Apatinib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Camrelizumab 200mg, every 3 weeks, intravenous infused. Apatinib 250mg, once a day, orally. Until progression or unacceptable toxicity events develop.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Camrelizumab</intervention_name>
    <description>Camrelizumab (Jiangsu HengRui Medicine Co., Ltd.) is a recombinant anti-human PD-1 IgG4 monoclonal antibody.</description>
    <arm_group_label>Camrelizumab combination with Apatinib</arm_group_label>
    <other_name>Camrelizumab for Injection</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Apatinib</intervention_name>
    <description>Apatinib is a novel angiogenesis inhibitor vascular endothelial growth factor 2.</description>
    <arm_group_label>Camrelizumab combination with Apatinib</arm_group_label>
    <other_name>Rivoceranib</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histopathologically confirmed advanced ICC, or combined hepatocellular and&#xD;
             cholangiocarcinoma (cHCC-CC, composition of cholangiocarcinoma &gt;50%). nonresectable or&#xD;
             metastatic cholangiocarcinoma and are not eligible for curative resection,&#xD;
             transplantation, or ablative therapies.&#xD;
&#xD;
          -  Have at least one measurable lesion (in accordance with RECIST v1.1); the measurable&#xD;
             lesion has a long diameter ≥ 10 mm or lymphadenopathy has a short diameter ≥ 15 mm in&#xD;
             spiral CT scan.&#xD;
&#xD;
          -  Child-Pugh Class: Grade A&#xD;
&#xD;
          -  ECOG-PS score 0 or 1&#xD;
&#xD;
          -  Life Expectancy of at least 3 months&#xD;
&#xD;
          -  Have the required screening laboratory values&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Extrahepatic cholangiocarcinoma (EHCC) and primary liver cancer. other active&#xD;
             malignant tumors except for ICC within 3 years or simultaneously. Cured localized&#xD;
             tumor, for example, basal cell carcinoma of skin, squamous cell carcinoma of skin,&#xD;
             superficial bladder cancer, carcinoma in situ of prostate, carcinoma in situs of&#xD;
             cervix, breast cancer in situ may be enrolled.&#xD;
&#xD;
          -  Any active autoimmune disease or history of autoimmune disease and expected recurrence&#xD;
             (including but not limited to autoimmune hepatitis, interstitial pneumonia, uveitis,&#xD;
             enteritis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism&#xD;
             [subjects that can be controlled with hormone replacement therapy only can be&#xD;
             enrolled]); subjects with skin diseases that does no need systemic treatment, for&#xD;
             example, leukoderma, psoriasis, alopecia, those with controlled type I diabetes by&#xD;
             insulin or those with asthma that has been completely resolved in childhood and with&#xD;
             no need of any intervention can be enrolled; while subjects with asthma who need&#xD;
             bronchodilator for medical intervention cannot be enrolled;&#xD;
&#xD;
          -  Use of strong CYP3A4/CYP2C19 inducers, including rifampicin (and its analogues) and&#xD;
             St. John's Wort, or strong CYP3A4/CYP2C19 inhibitors within two weeks prior to signing&#xD;
             informed consent form.&#xD;
&#xD;
          -  Previous treatment with other immune checkpoint inhibitors (include PD-1 antibody or&#xD;
             other immunotherapy against PD-1/PD-L1), or previous use of Apatinib.&#xD;
&#xD;
          -  Known history of serious allergy to any monoclonal antibody or Apatinib.&#xD;
&#xD;
          -  Inability or unwilling to swallow tablets, malabsorption syndrome or any condition&#xD;
             affecting gastrointestinal absorption.&#xD;
&#xD;
          -  Previous or current presence of metastasis to central nervous system.&#xD;
&#xD;
          -  Severe infection within 4 weeks prior to the start of study treatment, including but&#xD;
             not limited to hospitalization for infection, bacteremia or complications of severe&#xD;
             pneumonia; oral or intravenous therapeutic antibiotics within two weeks prior to the&#xD;
             start of study treatment (for example, subjects who are given with preventive&#xD;
             antibiotics for prevention of urinary tract infection or exacerbation of chronic&#xD;
             obstructive pulmonary disease are eligible for participation in the study);&#xD;
&#xD;
          -  Other factors that may affect the study results or lead to forced termination of the&#xD;
             study early as judged by investigators, such as alcoholism, drug abuse, other serious&#xD;
             diseases (including mental disorders) requiring concomitant therapy, with serious&#xD;
             laboratory examination abnormality, with family or social factors, that may affect&#xD;
             subject's safety.&#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_official>
    <last_name>Minshan Chen, MD., PhD.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Sun Yat-sen University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Li Xu, MD., PhD.</last_name>
    <phone>+862087343582</phone>
    <email>xuli@sysucc.org.cn</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Zhishan Lin</last_name>
    <phone>862087343437</phone>
    <email>linzhsh@sysucc.org.cn</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Li Xu</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <zip>510060</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Li Xu, MD.,PhD.</last_name>
      <phone>862087343582</phone>
      <email>xuli@sysucc.org.cn</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Sun Yat-sen University Cancer Center</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <zip>510060</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Li Xu, MD., PhD.</last_name>
      <phone>8620-87343115</phone>
      <email>xuli@sysucc.org.cn</email>
    </contact>
    <contact_backup>
      <last_name>Zhishan Lin</last_name>
      <phone>8620-87343437</phone>
      <email>linzhsh@sysucc.org.cn</email>
    </contact_backup>
    <investigator>
      <last_name>Minshan Chen, M.D.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>June 29, 2020</study_first_submitted>
  <study_first_submitted_qc>June 29, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 2, 2020</study_first_posted>
  <last_update_submitted>April 17, 2023</last_update_submitted>
  <last_update_submitted_qc>April 17, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 19, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Sun Yat-sen University</investigator_affiliation>
    <investigator_full_name>Chen Min-Shan</investigator_full_name>
    <investigator_title>Professor</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>Apatinib</mesh_term>
  </intervention_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/NCT04454905
org study id: B2020-098-01
nct id: NCT04454905
lead sponsor: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
This is a single arm, open-label, non-randomized and single-center phase II clinical study,
      to evaluate the safety, tolerance, and efficacy of Camrelizumab in combination with Apatinib
      in patients with advanced intrahepatic cholangiocarcinoma (ICC).
It is estimated that 50 patients who met the study criteria will be enrolled in 3 years and
      treated with Camrelizumab plus Apatinib in SYSUCC. The investigators will follow up and
      collect subjects' data to evaluate the efficacy and safety of treatment, including objective
      response rate (ORR) and Progression-free Survival (PFS) and Overall Survival (OS), until
      disease progression or death. Histopathology and multi-omics data analysis will be used to
      explore potential biomarkers of treatment response.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Progression-free Survival (PFS)
time frame: Three years
description: A duration from the date of initial treatment to disease progression (defined by RECIST 1.1) or death of any cause.
measure: Objective Response Rate (ORR)
time frame: Three years
description: Proportion of patients whose tumor volume has reached a predetermined value and can maintain a minimum time limit, including complete response and partial response patients.
measure: Overall Survival (OS)
time frame: Three years
description: Duration from the date of initial treatment to the date of death due to any cause.
measure: Disease Control Rate (DCR)
time frame: Two years
description: Proportion of patients whose tumor volume control (reduced or enlarged) reaches a predetermined value and can maintain a minimum time limit.
measure: Duration of Response (DoR)
time frame: Two years
description: Duration from the first time reported partial response or complete response to the first time of disease progression or death.
measure: Time to Progression (TTP)
time frame: Two years
description: A duration from the date of initial treatment to disease progression (defined by RECIST 1.1)
measure: Adverse events (AE)
time frame: Two years
description: Any adverse events related with treatment drugs and details include adverse events type, frequency and severity.
arm group label: Camrelizumab combination with Apatinib
arm group type: Experimental
description: Camrelizumab 200mg, every 3 weeks, intravenous infused. Apatinib 250mg, once a day, orally. Until progression or unacceptable toxicity events develop.
intervention type: Drug
intervention name: Camrelizumab
description: Camrelizumab (Jiangsu HengRui Medicine Co., Ltd.) is a recombinant anti-human PD-1 IgG4 monoclonal antibody.
arm group label: Camrelizumab combination with Apatinib
other name: Camrelizumab for Injection
intervention type: Drug
intervention name: Apatinib
description: Apatinib is a novel angiogenesis inhibitor vascular endothelial growth factor 2.
arm group label: Camrelizumab combination with Apatinib
other name: Rivoceranib
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Minshan Chen, MD., PhD.
role: Principal Investigator
affiliation: Sun Yat-sen University
last name: Li Xu, MD., PhD.
phone: +862087343582
email: xuli@sysucc.org.cn
last name: Zhishan Lin
phone: 862087343437
email: linzhsh@sysucc.org.cn
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Sun Yat-sen University
investigator full name: Chen Min-Shan
investigator title: Professor
mesh term: Cholangiocarcinoma
mesh term: Apatinib