<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/NCT03813784</url>
  </required_header>
  <id_info>
    <org_study_id>SHR-1210-III-311</org_study_id>
    <nct_id>NCT03813784</nct_id>
  </id_info>
  <brief_title>A Study to Evaluate SHR-1210 in Combination With Capecitabine + Oxaliplatin Sequenced by SHR-1210 + Apatinib as First-line Therapy in Treatment of Advanced Gastric Cancer</brief_title>
  <official_title>A Randomized, Multicenter, Open-Label, Phase 3 Study Comparing the Efficacy and Safety of SHR-1210 Plus Capecitabine and Oxaliplatin Sequenced by Apatinib With or Without SHR-1210 Versus Capecitabine and Oxaliplatin in Subjects With Previously Untreated Advanced or Metastatic Gastric or Gastroesophageal Junction Cancer</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>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a randomized, open-label, multi-center, phase III trial to evaluate the efficacy and&#xD;
      safety of SHR-1210 plus capecitabine and oxaliplatin sequenced by apatinib with or without&#xD;
      SHR-1210 versus capecitabine and oxaliplatin as first-line therapy in patients with locally&#xD;
      advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">March 7, 2019</start_date>
  <completion_date type="Anticipated">March 2023</completion_date>
  <primary_completion_date type="Anticipated">February 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>Overall survival (OS) of SHR-1210 in combination with capecitabine + oxaliplatin sequenced by SHR-1210+apatinib versus capecitabine + oxaliplatin in all subjects or programmed cell death ligand 1 (PD-L1) positive participants</measure>
    <time_frame>Up to 36 months after the first participant is randomized</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1</measure>
    <time_frame>Up to approximately 36 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free Survival (PFS) per RECIST 1.1</measure>
    <time_frame>Up to approximately 36 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Subjects with treatment-related adverse events (AEs)</measure>
    <time_frame>Up to approximately 36 months</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">887</enrollment>
  <condition>Gastric Cancer</condition>
  <condition>GastroEsophageal Cancer</condition>
  <arm_group>
    <arm_group_label>A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants receive SHR-1210 200 mg, intravenously (IV) every 3 weeks(Q3W) plus capecitabine 1000 mg/m^2 twice daily (BID) by continous oral adminstration for 14 days, followed by a recovery period of 7 days, plus oxaliplatin 130 mg/m^2, IV q3w; for 4-6 cycles followed by SHR-1210 plus apatinib 250 mg PO qd.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>B</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Capecitabine 1000 mg/m^2 twice daily (BID) by continous oral adminstration for 14 days, followed by a recovery period of 7 days, plus Oxaliplatin 130 mg/m^2, IV q3w</description>
  </arm_group>
  <arm_group>
    <arm_group_label>C</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants receive SHR-1210 200 mg, intravenously (IV) every 3 weeks(Q3W) plus capecitabine 1000 mg/m^2 twice daily (BID) by continous oral adminstration for 14 days, followed by a recovery period of 7 days, plus oxaliplatin 130 mg/m^2, IV q3w; for 4-6 cycles followed by SHR-1210</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>A</arm_group_label>
    <arm_group_label>C</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Capecitabine</intervention_name>
    <description>1000 mg/m^2 administered as continuous oral twice daily (BID) of each 3-week cycle.</description>
    <arm_group_label>A</arm_group_label>
    <arm_group_label>B</arm_group_label>
    <arm_group_label>C</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Oxaliplatin</intervention_name>
    <description>130 mg/m^2 administered IV Q3W on Day 1 of each 3-week cycle.</description>
    <arm_group_label>A</arm_group_label>
    <arm_group_label>B</arm_group_label>
    <arm_group_label>C</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Apatinib</intervention_name>
    <description>250 mg administered as continuous oral once daily (QD) of each 3-week cycle.</description>
    <arm_group_label>A</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Has histologically- or cytologically-confirmed diagnosis of locally advanced&#xD;
             unresectable or mestastatic adenocarcinoma of stomach or the esophagogastric junction&#xD;
             (GEJ)&#xD;
&#xD;
          -  Age ≥ 18 years old, male or female&#xD;
&#xD;
          -  NO previous therapy for advanced/metastatic disease of GC/GEJ (including HER-2&#xD;
             inhibitor). Subjects with previous adjuvant/neo-adjuvant therapy completed more than 6&#xD;
             months can be enrolled.&#xD;
&#xD;
          -  Has measurable disease per RECIST 1.1&#xD;
&#xD;
          -  Eastern Cooperative Group (ECOG) performance status of 0 to 1&#xD;
&#xD;
          -  Has adequate organ function&#xD;
&#xD;
          -  Females of childbearing potential (FOCBP), who are not surgically sterile or&#xD;
             postmenopausal, must conduct pregnancy test (serum or urine) within 7 days before&#xD;
             enrollment, and must not be pregnant or breast-feeding women. If the result is&#xD;
             negative, she must agree to use adequate contraception during the experiment and 3&#xD;
             months after the last administration of the test drugs. And non-sterilized males who&#xD;
             are sexually active must agree to use adequate contraception during the experiment and&#xD;
             3 months after the last administration of the test drugs.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Has known HER2-positive status&#xD;
&#xD;
          -  Has known active central nervous system metastatases&#xD;
&#xD;
          -  Has received a live vaccine within 4 weeks prior to the first dose of study treatment&#xD;
&#xD;
          -  With any acitve autoimmune disease or history of autoimmune disease, including but not&#xD;
             limited to the following: hepatititis, pneumonitis, uveitis, colitis (inflammatory&#xD;
             bowel disease), hypophysitis, vasculitis, nephritis, hyperthyroidism, and&#xD;
             hypothyroidism, except for subjects with vitiligo or resolved childhood asthma/atopy.&#xD;
             Asthma that requires intermittent use of bronchodilators or other medical intervention&#xD;
             should also be excluded.&#xD;
&#xD;
          -  Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibody, or&#xD;
             a VEGFR inhibitor.&#xD;
&#xD;
          -  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, Congestive heart failure (New York heart association (NYHA)&#xD;
             class &gt; 2), orventricular arrhythmia which need medical intervention.&#xD;
&#xD;
          -  Hypertension and unable to be controlled within normal level following treatment of&#xD;
             anti-hypertension agents: systolic blood pressure &gt; 140 mmHg, diastolic blood pressure&#xD;
             &gt; 90 mmHg.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Beijing Cancer Hospital, Peking University</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>August 2021</verification_date>
  <study_first_submitted>January 20, 2019</study_first_submitted>
  <study_first_submitted_qc>January 20, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 23, 2019</study_first_posted>
  <last_update_submitted>August 24, 2021</last_update_submitted>
  <last_update_submitted_qc>August 24, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">August 25, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>PD-1</keyword>
  <keyword>SHR-1210</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Stomach Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Capecitabine</mesh_term>
    <mesh_term>Oxaliplatin</mesh_term>
    <mesh_term>Apatinib</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03813784
org study id: SHR-1210-III-311
nct id: NCT03813784
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This is a randomized, open-label, multi-center, phase III trial to evaluate the efficacy and
      safety of SHR-1210 plus capecitabine and oxaliplatin sequenced by apatinib with or without
      SHR-1210 versus capecitabine and oxaliplatin as first-line therapy in patients with locally
      advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Overall survival (OS) of SHR-1210 in combination with capecitabine + oxaliplatin sequenced by SHR-1210+apatinib versus capecitabine + oxaliplatin in all subjects or programmed cell death ligand 1 (PD-L1) positive participants
time frame: Up to 36 months after the first participant is randomized
measure: Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
time frame: Up to approximately 36 months
measure: Progression-free Survival (PFS) per RECIST 1.1
time frame: Up to approximately 36 months
measure: Number of Subjects with treatment-related adverse events (AEs)
time frame: Up to approximately 36 months
arm group label: A
arm group type: Experimental
description: Participants receive SHR-1210 200 mg, intravenously (IV) every 3 weeks(Q3W) plus capecitabine 1000 mg/m^2 twice daily (BID) by continous oral adminstration for 14 days, followed by a recovery period of 7 days, plus oxaliplatin 130 mg/m^2, IV q3w; for 4-6 cycles followed by SHR-1210 plus apatinib 250 mg PO qd.
arm group label: B
arm group type: Active Comparator
description: Capecitabine 1000 mg/m^2 twice daily (BID) by continous oral adminstration for 14 days, followed by a recovery period of 7 days, plus Oxaliplatin 130 mg/m^2, IV q3w
arm group label: C
arm group type: Experimental
description: Participants receive SHR-1210 200 mg, intravenously (IV) every 3 weeks(Q3W) plus capecitabine 1000 mg/m^2 twice daily (BID) by continous oral adminstration for 14 days, followed by a recovery period of 7 days, plus oxaliplatin 130 mg/m^2, IV q3w; for 4-6 cycles followed by SHR-1210
intervention type: Drug
intervention name: SHR-1210
description: Subjects receive SHR-1210 intravenously, Dosage form: lyophilised powder, Strength: 200 mg /vial
arm group label: A
arm group label: C
intervention type: Drug
intervention name: Capecitabine
description: 1000 mg/m^2 administered as continuous oral twice daily (BID) of each 3-week cycle.
arm group label: A
arm group label: B
arm group label: C
intervention type: Drug
intervention name: Oxaliplatin
description: 130 mg/m^2 administered IV Q3W on Day 1 of each 3-week cycle.
arm group label: A
arm group label: B
arm group label: C
intervention type: Drug
intervention name: Apatinib
description: 250 mg administered as continuous oral once daily (QD) of each 3-week cycle.
arm group label: A
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: China
responsible party type: Sponsor
mesh term: Stomach Neoplasms
mesh term: Capecitabine
mesh term: Oxaliplatin
mesh term: Apatinib
sharing ipd: Undecided