<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/NCT04411706</url>
  </required_header>
  <id_info>
    <org_study_id>CTGU005</org_study_id>
    <nct_id>NCT04411706</nct_id>
  </id_info>
  <brief_title>A Study of Sintilimab Combined With Apatinib and Capecitabine in Advanced Hepatocellular Carcinoma</brief_title>
  <official_title>a Phase II, Open-label, Single Arm Study of Sintilimab (an Anti-PD-1 Inhibitor) Combined With Apatinib and Capecitabine in Advanced Hepatocellular Carcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Xin-Hua Xu</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>China Three Gorges University, Yichang, China</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 study aims to evaluate the efficacy and safety of Sintilimab (an Anti-PD-1 Inhibitor)&#xD;
      combined with apatinib and capecitabine as first-line therapy in patients with advanced&#xD;
      hepatocellular carcinoma.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">June 21, 2020</start_date>
  <completion_date type="Anticipated">June 1, 2022</completion_date>
  <primary_completion_date type="Anticipated">June 1, 2021</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>Objective Response Rate (ORR)</measure>
    <time_frame>1 year after the last patient's enrollment</time_frame>
    <description>Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Disease Control Rate (DCR)</measure>
    <time_frame>1 year after the last patient's enrollment</time_frame>
    <description>Disease Control Rate (DCR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response (DoR)</measure>
    <time_frame>1 year after the last patient's enrollment</time_frame>
    <description>Duration of Response (DoR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival(OS)</measure>
    <time_frame>1 year after the last patient's enrollment</time_frame>
    <description>the date of Death of any causes since the date of enrollment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival(PFS)</measure>
    <time_frame>1 year after the last patient's enrollment</time_frame>
    <description>Progression-free survival(PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety as measured by the rate of AEs</measure>
    <time_frame>1 year after the last patient's enrollment</time_frame>
    <description>The incidence and severity of adverse events (AEs) and serious adverse events (SAEs)</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">46</enrollment>
  <condition>Hepatocellular Carcinoma</condition>
  <arm_group>
    <arm_group_label>Sintilimab+Apatinib+Capecitabine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>=Drug: Sintilimab（i.v）+apatinib（p.o）+capecitabine（p.o）</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sintilimab Combined With Apatinib and Capecitabine</intervention_name>
    <description>Drug: Sintilimab 200mg (3mg/kg for underweight patients) intravenously, every 21 days for a cycle;&#xD;
Drug: Apatinib,250mg po qd, for continuous medication;&#xD;
Drug: Capecitabine,1000mg/m2 po bid, d1-d14, every 21 days for a cycle;</description>
    <arm_group_label>Sintilimab+Apatinib+Capecitabine</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patient has given written informed consent.&#xD;
&#xD;
          2. Age between 18-75 years old.male or female.&#xD;
&#xD;
          3. Conform to the clinical diagnosis standard strictly or histological or cytological&#xD;
             confirmation of HCC(hepatocellular carcinoma) and with at least one measurable lesion&#xD;
             by computed tomography (CT) scan or magnetic resonance imaging (MRI) according to&#xD;
             RECIST 1.1 standard.&#xD;
&#xD;
          4. Subjects haven't received any systemic treatment that includes target-therapy,&#xD;
             immunotherapy or chemotherapy for HCC before admission.&#xD;
&#xD;
          5. liver function status Child-Pugh Class A; Barcelona Clinic Liver Cancer(BCLC) staging&#xD;
             is stage B or C；&#xD;
&#xD;
          6. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1；&#xD;
&#xD;
          7. Expected survival ≥12 weeks&#xD;
&#xD;
          8. The main organ's function is normal and it should meet the following criteria(Excludes&#xD;
             use of any blood components and cell growth factors during the screening period):&#xD;
&#xD;
               1. Absolute neutrophil count≥1.5×109 /L&#xD;
&#xD;
               2. Platelets≥80×109/L ;Hemoglobin≥9.0 g/dL; Serum albumin≥3g/dL&#xD;
&#xD;
               3. Total bilirubin (TBIL)≤1.5×upper limit of normal (ULN); ALT and AST≤1.5×upper&#xD;
                  limit of normal(ULN); AKP≤ 2.5×upper limit of normal(ULN)&#xD;
&#xD;
               4. Thyroid stimulating hormone (TSH)≤1.0×upper limit of normal(ULN)（If abnormal, T3&#xD;
                  and T4 levels should be examined at the same time）&#xD;
&#xD;
               5. Serum creatinine ≤1.5×ULN or creatinine clearance &gt; 50 mL/minute (using&#xD;
                  Cockcroft-Gault formula)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients must not have had prior treatment with Sintilimab or any other PD-L1 or PD-1&#xD;
             antagonists.&#xD;
&#xD;
          2. Patients with any active autoimmune disease or history of autoimmune disease,&#xD;
             including but not limited to the following: hepatitis, pneumonitis, uveitis, colitis&#xD;
             (inflammatory bowel disease), hypophysitis, vasculitis, nephritis, hyperthyroidism,&#xD;
             and hypothyroidism, except for subjects with vitiligo or resolved childhood&#xD;
             asthma/atopy. Asthma that requires intermittent use of bronchodilators or other&#xD;
             medical intervention should also be excluded.&#xD;
&#xD;
          3. Concurrent medical condition requiring the use of immunosuppressive medications, or&#xD;
             immunosuppressive doses of systemic or absorbable topical corticosteroids. Doses &gt; 10&#xD;
             mg/day prednisone or equivalent are prohibited within 2 weeks before study drug&#xD;
             administration. Note: corticosteroids used for the purpose of IV contrast allergy&#xD;
             prophylaxis are allowed.&#xD;
&#xD;
          4. Known history of hypersensitivity to any components of the Sintilimab formulation, or&#xD;
             other antibody formulation.&#xD;
&#xD;
          5. Active central nervous system (CNS) metastases with clinical symptoms (including&#xD;
             cerebral edema, steroid requirement, or progressive disease).&#xD;
&#xD;
          6. Patients with other malignant tumor (except cured skin basal cell carcinoma and&#xD;
             cervical carcinoma).&#xD;
&#xD;
          7. Clinically significant cardiovascular and cerebrovascular diseases, including but not&#xD;
             limited to severe acute myocardial infarction within 6 months before enrollment,&#xD;
             unstable or severe angina, or coronary artery bypass surgery, Congestive heart failure&#xD;
             (New York heart association (NYHA) class &gt; 2), ventricular arrhythmia which need&#xD;
             medical intervention, left ventricular ejection fraction(LVEF) &lt; 50%.&#xD;
&#xD;
          8. Hypertension and unable to be controlled within normal level following treatment of&#xD;
             anti-hypertension agents(within 3 months): systolic blood pressure &gt; 140 mmHg,&#xD;
             diastolic blood pressure &gt; 90 mmHg.&#xD;
&#xD;
          9. Coagulation abnormalities (PT&gt;16s、APTT&gt;43s、TT&gt;21s、Fbg&lt;2g/L), with bleeding tendency or&#xD;
             are receiving thrombolytic or anticoagulant therapy. Patients with or previous with&#xD;
             serious hemorrhage (bleeding &gt; 30 ml within 3 months), haemoptysis (&gt; 5 ml within 4&#xD;
             weeks) of thromboembolic events within 12 months (including stroke events and/or&#xD;
             transient ischemic attack).&#xD;
&#xD;
         10. Previous digestive tract bleeding history within 3 months or evident gastrointestinal&#xD;
             bleeding tendency, such as: esophageal varices, local active ulcerative lesions,&#xD;
             gastric ulcer and duodenal ulcer, the ulcerous colitis, gastrointestinal diseases such&#xD;
             as portal hypertension or resection of tumor with bleeding risk, etc.&#xD;
&#xD;
         11. Objective evidence of previous or current pulmonary fibrosis history, interstitial&#xD;
             pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonia, pulmonary&#xD;
             function damaged seriously etc.&#xD;
&#xD;
         12. History of immunodeficiency including seropositivity for human immunodeficiency virus&#xD;
             (HIV), or other acquired or congenital immune-deficient disease, or active hepatitis&#xD;
             (transaminase does not meet the inclusion, hepatitis B virus (HBV) DNA ≥10⁴ /ml or&#xD;
             hepatitis C virus (HCV) RNA≥103 /ml or higher)&#xD;
&#xD;
         13. Participated in other clinical trials, or finish other clinical trials within 4 weeks.&#xD;
             Patients who may receive other anti-tumor systemic chemotherapy during the study.&#xD;
&#xD;
         14. Patients who may receive vaccination during the study, or previous had vaccination&#xD;
             within 4 weeks.&#xD;
&#xD;
         15. Any other medical, psychiatric, or social condition deemed by the investigator to be&#xD;
             likely to interfere with a subject's rights, safety, welfare, or ability to sign&#xD;
             informed consent, cooperate, and participate in the study or would interfere with the&#xD;
             interpretation of the results.&#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>Xinhua Xu, Master</last_name>
    <phone>+8613986747496</phone>
    <phone_ext>+8613986747496</phone_ext>
    <email>2732774352@qq.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Lu Xu, Phd</last_name>
    <phone>+8613972032135</phone>
    <email>xlnick@qq.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Department of Medical Oncology, Central Hospital of Yichang City, the First Clinical Medical College of Three Gorges University</name>
      <address>
        <city>Yichang</city>
        <state>Hubei</state>
        <zip>443003</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Xinhua Xu</last_name>
      <phone>+8613986747496</phone>
      <phone_ext>+8613986747496</phone_ext>
      <email>2732774352@qq.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>May 28, 2020</study_first_submitted>
  <study_first_submitted_qc>May 28, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 2, 2020</study_first_posted>
  <last_update_submitted>June 22, 2020</last_update_submitted>
  <last_update_submitted_qc>June 22, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 24, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>China Three Gorges University, Yichang, China</investigator_affiliation>
    <investigator_full_name>Xin-Hua Xu</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>Carcinoma</mesh_term>
    <mesh_term>Carcinoma, Hepatocellular</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Capecitabine</mesh_term>
    <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/NCT04411706
org study id: CTGU005
nct id: NCT04411706
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
This study aims to evaluate the efficacy and safety of Sintilimab (an Anti-PD-1 Inhibitor)
      combined with apatinib and capecitabine as first-line therapy in patients with advanced
      hepatocellular carcinoma.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Objective Response Rate (ORR)
time frame: 1 year after the last patient's enrollment
description: Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1).
measure: Disease Control Rate (DCR)
time frame: 1 year after the last patient's enrollment
description: Disease Control Rate (DCR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1).
measure: Duration of Response (DoR)
time frame: 1 year after the last patient's enrollment
description: Duration of Response (DoR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1).
measure: Overall survival(OS)
time frame: 1 year after the last patient's enrollment
description: the date of Death of any causes since the date of enrollment
measure: Progression-free survival(PFS)
time frame: 1 year after the last patient's enrollment
description: Progression-free survival(PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1).
measure: Safety as measured by the rate of AEs
time frame: 1 year after the last patient's enrollment
description: The incidence and severity of adverse events (AEs) and serious adverse events (SAEs)
arm group label: Sintilimab+Apatinib+Capecitabine
arm group type: Experimental
description: =Drug: Sintilimab（i.v）+apatinib（p.o）+capecitabine（p.o）
intervention type: Drug
intervention name: Sintilimab Combined With Apatinib and Capecitabine
description: Drug: Sintilimab 200mg (3mg/kg for underweight patients) intravenously, every 21 days for a cycle;
Drug: Apatinib,250mg po qd, for continuous medication;
Drug: Capecitabine,1000mg/m2 po bid, d1-d14, every 21 days for a cycle;
arm group label: Sintilimab+Apatinib+Capecitabine
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Xinhua Xu, Master
phone: +8613986747496
phone ext: +8613986747496
email: 2732774352@qq.com
last name: Lu Xu, Phd
phone: +8613972032135
email: xlnick@qq.com
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Sponsor-Investigator
investigator affiliation: China Three Gorges University, Yichang, China
investigator full name: Xin-Hua Xu
investigator title: professor
mesh term: Carcinoma
mesh term: Carcinoma, Hepatocellular
mesh term: Capecitabine
mesh term: Apatinib