<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/NCT03764293</url>
  </required_header>
  <id_info>
    <org_study_id>SHR-1210-III-310</org_study_id>
    <nct_id>NCT03764293</nct_id>
  </id_info>
  <brief_title>A Study to Evaluate SHR-1210 in Combination With Apatinib as First-Line Therapy in Patients With Advanced HCC</brief_title>
  <official_title>A Randomized, Open-Label, International, Multi-Center, Phase 3 Clinical Study of PD-1 Antibody SHR-1210 Plus Apatinib Mesylate Versus Sorafenib as First-Line Therapy in Patients With Advanced Hepatocellular Carcinoma (HCC) Who Have Not Previously Received Systemic Therapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Jiangsu HengRui Medicine Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Jiangsu HengRui Medicine Co., Ltd.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a randomized, open-label, international, multi-center, phase III trial to evaluate&#xD;
      the efficacy and safety of SHR-1210 plus apatinib mesylate versus sorafenib as first-line&#xD;
      therapy in patients with advanced HCC.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">June 10, 2019</start_date>
  <completion_date type="Anticipated">July 2023</completion_date>
  <primary_completion_date type="Actual">February 8, 2022</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>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 compare the overall survival (OS) of SHR-1210 plus apatinib with sorafenib</measure>
    <time_frame>Up to approximately 3 years</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>To compare the progression-free survival (PFS) of SHR-1210 plus apatinib with sorafenib</measure>
    <time_frame>Up to approximately 3 years</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>To compare the time to progression (TTP) of SHR-1210 plus apatinib with sorafenib</measure>
    <time_frame>Up to approximately 3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To compare objective response rate (ORR) of SHR-1210 plus apatinib with sorafenib</measure>
    <time_frame>Up to approximately 3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To compare disease control rate (DCR) of SHR-1210 plus apatinib with sorafenib</measure>
    <time_frame>Up to approximately 3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To compare duration of response (DoR) of SHR-1210 plus apatinib with sorafenib</measure>
    <time_frame>Up to approximately 3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The incidence and severity of adverse events (AEs) and serious adverse events (SAEs) of SHR-1210 plus apatinib versus sorafenib as assessed by CTCAE v4.03</measure>
    <time_frame>Up to approximately 3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum concentration of SHR-1210 and plasma concentration of apatinib</measure>
    <time_frame>Up to approximately 3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of anti-SHR-1210 antibody (ADA) and neutralizing antibody (Nab) formed during the study from baseline</measure>
    <time_frame>Up to approximately 3 years</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>To evaluate the time to deteriation (TTD) of SHR-1210 plus apatinib versus sorafenib</measure>
    <time_frame>Up to approximately 3 years</time_frame>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">543</enrollment>
  <condition>Locally Advanced or Metastatic and Unresectable HCC</condition>
  <arm_group>
    <arm_group_label>SHR-1210</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>SHR-1210+Apatinib</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Sorafenib</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>SHR-1210</intervention_name>
    <description>Subjects receive SHR-1210 intravenously, Dosage form: lyophilised powder, Strength: 200 mg /vial</description>
    <arm_group_label>SHR-1210</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Apatinib</intervention_name>
    <description>Subjects receive Apatinib orally, Dosage form: tablet, Strength: 250 mg/tablet</description>
    <arm_group_label>SHR-1210</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sorafenib</intervention_name>
    <description>Subjects receive Sorafenib orally, Dosage form: tablet, Strength: 0.2 g/tablet</description>
    <arm_group_label>Control</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histopathologically or cytologically confirmed advanced HCC&#xD;
&#xD;
          -  No previous systematic treatment for HCC&#xD;
&#xD;
          -  Have at least one measurable lesion (in accordance with RECIST v1.1)&#xD;
&#xD;
          -  BCLC stage B or C, and not suitable for surgical or local therapy, or has progressed&#xD;
             following surgical and/or local therapy&#xD;
&#xD;
          -  ECOG-PS score 0 or 1&#xD;
&#xD;
          -  Child-Pugh Class: Grade A&#xD;
&#xD;
          -  Life Expectancy of at least 12 weeks&#xD;
&#xD;
          -  Subjects with HBV infection: HBV DNA&lt;500 IU/ml or &lt; 2500 copy/mL, and have received&#xD;
             anti-HBV therapy for at least 14 days prior to enrollment in the study&#xD;
&#xD;
          -  Subjects with HCV-RNA(+) must receive antiviral therapy&#xD;
&#xD;
          -  Adequate organ function&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Known hepatocholangiocarcinoma, sarcomatoid HCC, mixed cell carcinoma and lamellar&#xD;
             cell carcinoma; other active malignant tumor except HCC within 5 years or&#xD;
             simultaneously&#xD;
&#xD;
          -  Moderate-to-severe ascites with clinical symptoms&#xD;
&#xD;
          -  History of gastrointestinal hemorrhage within 6 months prior to the start of study&#xD;
             treatment or clear tendency of gastrointestinal hemorrhage&#xD;
&#xD;
          -  Abdominal fistula, gastrointestinal perforation or intraperitoneal abscess within 6&#xD;
             months prior to the start of study treatment&#xD;
&#xD;
          -  Known genetic or acquired hemorrhage or thrombotic tendency&#xD;
&#xD;
          -  Thrombosis or thromboembolic event within 6 months prior to the start of study&#xD;
             treatment&#xD;
&#xD;
          -  Cardiac clinical symptom or disease that is not well controlled&#xD;
&#xD;
          -  Hypertension that can not be well controlled through antihypertensive drugs&#xD;
&#xD;
          -  Factors to affect oral administration&#xD;
&#xD;
          -  History of hepatic encephalopathy&#xD;
&#xD;
          -  Previous or current presence of metastasis to central nervous system&#xD;
&#xD;
          -  HIV infection&#xD;
&#xD;
          -  Combined hepatitis B and hepatitis C co-infection&#xD;
&#xD;
          -  Be ready for or previously received organ or allogenic bone marrow transplantation&#xD;
&#xD;
          -  Interstitial lung disease that is symptomatic or may interfere with the detection and&#xD;
             management of suspected drug-related pulmonary toxicity&#xD;
&#xD;
          -  Active known, or suspected autoimmune disease&#xD;
&#xD;
          -  Subjects with a condition requiring systemic treatment with either corticosteroids or&#xD;
             other immunosuppressive medications within 14 days of first administration of study&#xD;
             treatment&#xD;
&#xD;
          -  Use of potent CYP3A4 inducers or inhibitors within 2 weeks prior to the signature of&#xD;
             ICF&#xD;
&#xD;
          -  Known history of serious allergy to any monoclonal antibody or targeted&#xD;
             anti-angiogenic drug&#xD;
&#xD;
          -  Severe infection within 4 weeks prior to the start of study treatment&#xD;
&#xD;
          -  Palliative radiotherapy for non-target lesions to control symptoms is allowed, but it&#xD;
             must be completed at least 2 weeks prior to the start of study treatment&#xD;
&#xD;
          -  Treatment of other investigational product(s) within 28 days prior to the start of&#xD;
             study treatment&#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>Shukui Qin, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Eastern Theater General Hospital,QinHuai District Medical Area</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Beverly Hills Cancer Center</name>
      <address>
        <city>Beverly Hills</city>
        <state>California</state>
        <zip>90211</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California San Diego (UCSD)-Moores Cancer Center</name>
      <address>
        <city>La Jolla</city>
        <state>California</state>
        <zip>92037</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California - Irvine</name>
      <address>
        <city>Orange</city>
        <state>California</state>
        <zip>92868</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Maryland</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cornell University Weill Cornell Medical College</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Center for Cancer and Blood Disorders</name>
      <address>
        <city>Fort Worth</city>
        <state>Texas</state>
        <zip>76104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MD Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Renovatio Clinical</name>
      <address>
        <city>The Woodlands</city>
        <state>Texas</state>
        <zip>77380</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cliniques Universitaires de Bruxelles Hopital Erasme</name>
      <address>
        <city>Bruxelles</city>
        <zip>1070</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cliniques Universitaires Saint-Luc</name>
      <address>
        <city>Bruxelles</city>
        <zip>1200</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UZA</name>
      <address>
        <city>Edegem</city>
        <zip>2650</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AZ Maria Middelares</name>
      <address>
        <city>Gent</city>
        <zip>9000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AZ Groeninge</name>
      <address>
        <city>Kortrijk</city>
        <zip>8500</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Anhui Provincal Cancer Hospital</name>
      <address>
        <city>Hefei</city>
        <state>Anhui</state>
        <zip>230000</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Anhui Provincal Hospital</name>
      <address>
        <city>Hefei</city>
        <state>Anhui</state>
        <zip>230000</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The First Affiliated Hospital Of Anhui Medical University</name>
      <address>
        <city>Hefei</city>
        <state>Anhui</state>
        <zip>230009</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Second Affiliated Hospital Of Anhui Medical University</name>
      <address>
        <city>Hefei</city>
        <state>Anhui</state>
        <zip>230601</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chinese Academy of Medical Sciences Cancer Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100020</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Beijing cancer Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100089</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Peking University International Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>102206</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Second Hospital Affiliated To AMU</name>
      <address>
        <city>Chongqing</city>
        <state>Chongqing</state>
        <zip>400037</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The First Hospital Affiliated To AMU</name>
      <address>
        <city>Chongqing</city>
        <state>Chongqing</state>
        <zip>400038</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>TheThird Affiliated Hospital ,Army Medical University</name>
      <address>
        <city>Chongqing</city>
        <state>Chongqing</state>
        <zip>400042</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Second Affiliated Hospital of ChongQing Medical University</name>
      <address>
        <city>Chongqing</city>
        <state>Chongqing</state>
        <zip>400060</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fujian Medical University Union Hospital</name>
      <address>
        <city>Fuzhou</city>
        <state>Fujian</state>
        <zip>350001</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The 940th Hospital of the joint logistic support force of People's Liberation Army</name>
      <address>
        <city>Lanzhou</city>
        <state>Gansu</state>
        <country>China</country>
      </address>
    </facility>
  </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>
  </location>
  <location>
    <facility>
      <name>Sun Yat-sen Memorial Hospital, Sun Yat-Sen University</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <zip>510220</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NanFang Hospital of Southern Medical University</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <zip>510515</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The first affiliated hospital of guangxi medical university</name>
      <address>
        <city>Nanning</city>
        <state>Guangxi</state>
        <zip>530021</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Fourth Hospital of Hebei Medical University</name>
      <address>
        <city>Shijiazhuang</city>
        <state>Hebei</state>
        <zip>050011</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Harbin Medical University Cancer Hospital</name>
      <address>
        <city>Harbin</city>
        <state>Heilongjiang</state>
        <zip>150000</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wuhan Union Hospital,Tongji Medical College,Huazhong University of Science&amp;Technology</name>
      <address>
        <city>Wuhan</city>
        <state>Hubei</state>
        <zip>430022</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tongji hospital,Tongji Medical College,Huazhong University of Science&amp;Technology</name>
      <address>
        <city>Wuhan</city>
        <state>Hubei</state>
        <zip>430030</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hunan Cancer Hospital</name>
      <address>
        <city>Changsha</city>
        <state>Hunan</state>
        <zip>410006</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Eastern Theater General Hospital, Qinhuai District Medical Area</name>
      <address>
        <city>Nanjing</city>
        <state>Jiangsu</state>
        <zip>210002</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The First Affiliated Hospital Of Nanchang University</name>
      <address>
        <city>Nanchang</city>
        <state>Jiangxi</state>
        <zip>330006</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Jilin Cancer Hospital</name>
      <address>
        <city>Changchun</city>
        <state>Jilin</state>
        <zip>130000</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The First Hospital of Jilin University</name>
      <address>
        <city>Changchun</city>
        <state>Jilin</state>
        <zip>130000</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Sixth People's Hospital of Shengyang</name>
      <address>
        <city>Shengyang</city>
        <state>Liaoning</state>
        <zip>110006</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Liaoning Cancer Hospital</name>
      <address>
        <city>Shenyang</city>
        <state>Liaoning</state>
        <zip>110042</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shandong Cancer Hospital Affiliated to Shandong University</name>
      <address>
        <city>Jinan</city>
        <state>Shandong</state>
        <zip>250000</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fudan University Shanghai Cancer Center</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200032</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Zhongshan Hospital, Fudan University</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200032</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shanghai Changhai Hospital</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200043</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>West China Hospital of Sichuan University</name>
      <address>
        <city>Chengdu</city>
        <state>Si Chuan</state>
        <zip>610041</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sichuan Cancer Hospital&amp;Institute</name>
      <address>
        <city>Chengdu</city>
        <state>Sichuan</state>
        <zip>610054</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sir Run Run Shaw Hospital</name>
      <address>
        <city>Hangzhou</city>
        <state>Zhejiang</state>
        <zip>310016</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ZheJiang Cancer Hospital</name>
      <address>
        <city>Hangzhou</city>
        <state>Zhejiang</state>
        <zip>310022</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The First Affiliated Hospital, Zhejiang University</name>
      <address>
        <city>Hangzhou</city>
        <state>Zhejiang</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Charite Universitaetsmedizin Berlin - Campus Virchow-Klinikum Berlin</name>
      <address>
        <city>Berlin</city>
        <zip>13353</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pamela Youde Nethersole Eastern Hospital</name>
      <address>
        <city>Hong Kong</city>
        <country>Hong Kong</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The University of Hong Kong</name>
      <address>
        <city>Hong Kong</city>
        <country>Hong Kong</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tuen Mun Hospital</name>
      <address>
        <city>Hong Kong</city>
        <country>Hong Kong</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Chinese University of Hong Kong</name>
      <address>
        <city>Shatin</city>
        <country>Hong Kong</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>A.S.L. Napoli 1 Centro Ospedale del Mare</name>
      <address>
        <city>Ponticelli</city>
        <state>Napoli</state>
        <zip>80147</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi IRCCS</name>
      <address>
        <city>Bologna</city>
        <zip>40138</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (Presidio Spedali Civili)</name>
      <address>
        <city>Brescia</city>
        <zip>25123</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliero-Universitaria</name>
      <address>
        <city>Cagliari</city>
        <zip>09124</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera Universitaria Careggi</name>
      <address>
        <city>Firenze</city>
        <zip>50134</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico</name>
      <address>
        <city>Milano</city>
        <zip>20122</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fondazione Policlinico Universitario Agostino Gemelli IRCCS</name>
      <address>
        <city>Roma</city>
        <zip>00168</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera Universitaria Integrata Verona (Ospedale Borgo Roma)</name>
      <address>
        <city>Verona</city>
        <zip>37134</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seoul National University Bundang Hospital Gyeonggi-do</name>
      <address>
        <city>Seongnam-si</city>
        <state>Gyeonggi-do</state>
        <zip>13620</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Catholic University of Korea, St. Vincent's Hospital</name>
      <address>
        <city>Suwon-si</city>
        <state>Gyeonggi-do</state>
        <zip>16247</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ajou University Hospital</name>
      <address>
        <city>Suwon</city>
        <state>Gyeonggi-do</state>
        <zip>16499</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dong-A University Hospital</name>
      <address>
        <city>Busan</city>
        <zip>602715</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Korea University Anam Hospital</name>
      <address>
        <city>Seoul</city>
        <zip>02481</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Severance Hospital, Yonsei University Health System</name>
      <address>
        <city>Seoul</city>
        <zip>03722</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Asan Medical Center</name>
      <address>
        <city>Seoul</city>
        <zip>05505</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Samsung Medical Center</name>
      <address>
        <city>Seoul</city>
        <zip>06351</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centrum Medyczne Pratia Gdynia</name>
      <address>
        <city>Gdynia</city>
        <zip>81338</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centrum Onkologii-Instytut im.M.Sklodowskiej Curie</name>
      <address>
        <city>Gliwice</city>
        <zip>44101</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pratia MCM Krakow</name>
      <address>
        <city>Krakow</city>
        <zip>30510</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Przychodnia Med-Polonia Sp. z o.o.</name>
      <address>
        <city>Poznan</city>
        <zip>60693</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wielkopolskie Centrum Onkologii</name>
      <address>
        <city>Poznan</city>
        <zip>61866</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centrum Zdrowia MDM</name>
      <address>
        <city>Warszawa</city>
        <zip>00635</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy</name>
      <address>
        <city>Warszawa</city>
        <zip>02034</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NZOZ Centrum Badan Klinicznych</name>
      <address>
        <city>Wroclaw</city>
        <zip>51162</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SBIH of Arkhangelsk region &quot;Arkhangelsk Clinical Oncological Dispensary&quot;</name>
      <address>
        <city>Arkhangelsk</city>
        <zip>164045</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SBHI Chelyabinsk Regional Clinical Center for Oncology and Nuclear Medicine</name>
      <address>
        <city>Chelyabinsk</city>
        <zip>454087</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Irkutsk Regional Oncology Dispensary</name>
      <address>
        <city>Irkutsk</city>
        <zip>664035</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SBIH &quot; Clinical Oncological Dispensary # 1&quot;</name>
      <address>
        <city>Krasnodar</city>
        <zip>350040</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>RBIH &quot;Kursk regional clinical oncology dispensary&quot; of Kursk Region Healthcare Committee</name>
      <address>
        <city>Kursk</city>
        <zip>305035</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>&quot;VitaMed&quot; LLC</name>
      <address>
        <city>Moscow</city>
        <zip>121309</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SBIH of Moscow city &quot;Moscow city oncology hospital №62&quot; of Moscow Healthcare departement</name>
      <address>
        <city>Moscow</city>
        <zip>143423</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CJSC Avicenna</name>
      <address>
        <city>Novosibirsk</city>
        <zip>630099</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>BHI of Omsk region &quot;Clinical Oncology Dispensary&quot;</name>
      <address>
        <city>Omsk</city>
        <zip>644013</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pavlov First Saint Petersburg State Medical University</name>
      <address>
        <city>Saint-Petersburg</city>
        <zip>197022</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SPb SBIH &quot;City Clinical Oncological Dispensary&quot;</name>
      <address>
        <city>Saint-Petersburg</city>
        <zip>197022</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>FBI &quot;Scientific Research Institute of Oncology n. a. N. N. Petrov&quot;</name>
      <address>
        <city>Saint-Petersburg</city>
        <zip>197758</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SBIH Republican Clinical Oncological Dispensary of the MoH of Republic Bashkortostan</name>
      <address>
        <city>Ufa</city>
        <zip>450054</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Reina Sofia</name>
      <address>
        <city>Cordoba</city>
        <state>Córdoba</state>
        <zip>14004</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Ramon y Cajal</name>
      <address>
        <city>Madrid</city>
        <zip>28034</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Clinico San Carlos</name>
      <address>
        <city>Madrid</city>
        <zip>28040</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario 12 de Octubre</name>
      <address>
        <city>Madrid</city>
        <zip>28041</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario La Paz</name>
      <address>
        <city>Madrid</city>
        <zip>28046</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario HM Madrid Sanchinarro</name>
      <address>
        <city>Madrid</city>
        <zip>28050</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitari i Politecnic La Fe</name>
      <address>
        <city>Valencia</city>
        <zip>46026</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Changhua Christian Medical Foundation Changhua Christian Hospital</name>
      <address>
        <city>Changhua</city>
        <zip>500006</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chang Gung Memorial Hospital, Chiayi</name>
      <address>
        <city>Chiayi City</city>
        <zip>613</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>E-DA Cancer Hospital</name>
      <address>
        <city>Kaohsiung</city>
        <zip>82445</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaohsiung Chang Gung Memorial Hospital</name>
      <address>
        <city>Kaohsiung</city>
        <zip>833</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Cheng Kung University Hospital</name>
      <address>
        <city>Tainan</city>
        <zip>704</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Taiwan University Hospital</name>
      <address>
        <city>Taipei</city>
        <zip>100</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Taipei Veterans General Hospital</name>
      <address>
        <city>Taipei</city>
        <zip>11217</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chang Gung Memorial Hospital, Linkou</name>
      <address>
        <city>Taoyuan</city>
        <zip>333</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baskent University Adana Application and Research Center</name>
      <address>
        <city>Adana</city>
        <zip>01229</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dr. Abdurrahman Yurtaslan Oncology Teaching and Research Hospital</name>
      <address>
        <city>Ankara</city>
        <zip>06105</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ankara City Hospital</name>
      <address>
        <city>Ankara</city>
        <zip>06800</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istanbul University Cerrahpasa - Cerrahpasa Medical Faculty</name>
      <address>
        <city>Istanbul</city>
        <zip>34098</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bakirkoy Dr. Sadi Konuk Teaching and Research Hospital</name>
      <address>
        <city>Istanbul</city>
        <zip>34147</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Inonu Uni. Med. Fac.</name>
      <address>
        <city>Malatya</city>
        <zip>44280</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CNE&quot;City Clin Hosp#4&quot;of Dnipro City Council Dept of Chemotherapy SI Dnipropetrovsk MA of MOHU</name>
      <address>
        <city>Dnipro</city>
        <zip>49102</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Communal Non-profit Enterprise Regional Center of Oncology</name>
      <address>
        <city>Kharkiv</city>
        <zip>61070</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CI of Healthcare Regional Clinical Specialized Dispensary of the Radiation Protection</name>
      <address>
        <city>Kharkiv</city>
        <zip>61166</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical Center of Limited Liability Company Medical Center Concilium Medical</name>
      <address>
        <city>Kyiv</city>
        <zip>04050</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Communal Enterprise Volyn Regional Medical Center of Oncology of Volyn Regional Council</name>
      <address>
        <city>Lutsk</city>
        <zip>43018</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Communal Institution Odesa Regional Clinical Hospital</name>
      <address>
        <city>Odesa</city>
        <zip>65025</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CNCE of SRC Sumy Reg Clinical Oncology Dispensary, SSU, Chair of Oncology and Radiology</name>
      <address>
        <city>Sumy</city>
        <zip>40022</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Zaporizhzhya City Clinical Hospital #3</name>
      <address>
        <city>Zaporizhzhia</city>
        <zip>69032</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
    <country>China</country>
    <country>Germany</country>
    <country>Hong Kong</country>
    <country>Italy</country>
    <country>Korea, Republic of</country>
    <country>Poland</country>
    <country>Russian Federation</country>
    <country>Spain</country>
    <country>Taiwan</country>
    <country>Turkey</country>
    <country>Ukraine</country>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>November 28, 2018</study_first_submitted>
  <study_first_submitted_qc>December 3, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 5, 2018</study_first_posted>
  <last_update_submitted>June 18, 2023</last_update_submitted>
  <last_update_submitted_qc>June 18, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 22, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sorafenib</mesh_term>
    <mesh_term>Apatinib</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03764293
org study id: SHR-1210-III-310
nct id: NCT03764293
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is a randomized, open-label, international, multi-center, phase III trial to evaluate
      the efficacy and safety of SHR-1210 plus apatinib mesylate versus sorafenib as first-line
      therapy in patients with advanced HCC.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: To compare the overall survival (OS) of SHR-1210 plus apatinib with sorafenib
time frame: Up to approximately 3 years
measure: To compare the progression-free survival (PFS) of SHR-1210 plus apatinib with sorafenib
time frame: Up to approximately 3 years
measure: To compare the time to progression (TTP) of SHR-1210 plus apatinib with sorafenib
time frame: Up to approximately 3 years
measure: To compare objective response rate (ORR) of SHR-1210 plus apatinib with sorafenib
time frame: Up to approximately 3 years
measure: To compare disease control rate (DCR) of SHR-1210 plus apatinib with sorafenib
time frame: Up to approximately 3 years
measure: To compare duration of response (DoR) of SHR-1210 plus apatinib with sorafenib
time frame: Up to approximately 3 years
measure: The incidence and severity of adverse events (AEs) and serious adverse events (SAEs) of SHR-1210 plus apatinib versus sorafenib as assessed by CTCAE v4.03
time frame: Up to approximately 3 years
measure: Serum concentration of SHR-1210 and plasma concentration of apatinib
time frame: Up to approximately 3 years
measure: Proportion of anti-SHR-1210 antibody (ADA) and neutralizing antibody (Nab) formed during the study from baseline
time frame: Up to approximately 3 years
measure: To evaluate the time to deteriation (TTD) of SHR-1210 plus apatinib versus sorafenib
time frame: Up to approximately 3 years
arm group label: SHR-1210
arm group type: Experimental
description: SHR-1210+Apatinib
arm group label: Control
arm group type: Active Comparator
description: Sorafenib
intervention type: Drug
intervention name: SHR-1210
description: Subjects receive SHR-1210 intravenously, Dosage form: lyophilised powder, Strength: 200 mg /vial
arm group label: SHR-1210
intervention type: Drug
intervention name: Apatinib
description: Subjects receive Apatinib orally, Dosage form: tablet, Strength: 250 mg/tablet
arm group label: SHR-1210
intervention type: Drug
intervention name: Sorafenib
description: Subjects receive Sorafenib orally, Dosage form: tablet, Strength: 0.2 g/tablet
arm group label: Control
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Shukui Qin, MD
role: Principal Investigator
affiliation: Eastern Theater General Hospital,QinHuai District Medical Area
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country: Belgium
country: China
country: Germany
country: Hong Kong
country: Italy
country: Korea, Republic of
country: Poland
country: Russian Federation
country: Spain
country: Taiwan
country: Turkey
country: Ukraine
country: United States
responsible party type: Sponsor
mesh term: Sorafenib
mesh term: Apatinib
sharing ipd: No