<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/NCT03755440</url>
  </required_header>
  <id_info>
    <org_study_id>EBVaGC-SYSUCC</org_study_id>
    <nct_id>NCT03755440</nct_id>
  </id_info>
  <brief_title>PD-1 Antibody in EBV Positive Metastatic Gastric Cancer Patients.</brief_title>
  <official_title>Phase II Study of PD-1 Antibody SHR-1210 in EBV Positive Metastatic Gastric Cancer Patients.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sun Yat-sen University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sun Yat-sen University</source>
  <oversight_info>
    <has_dmc>No</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>
      EBV positive tumor accounts for 8-9% of all gastric cancer (GC) patients. PD-1 antibody has&#xD;
      been proved as third line therapy for PD-L1 positive gastric cancer. Previous studies showed&#xD;
      that EBV(+) tumors exhibit high response to PD-1 antibody. In this phase II study, we will&#xD;
      investigate the efficacy and safety of PD-1 antibody in EBV positive metastatic GC patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      EBV positive metastatic GC patients who failed to standard chemotherapy will receive therapy&#xD;
      of single agent, PD-1 antibody, SHR-1210, 200mg, every 2 weeks. The primary endpoint is&#xD;
      response rate. Secondary endpoint is progress free survival, overall survival, safety and&#xD;
      quality of life. Using the Simon two-stage sample size calculation, the sample size is 19. We&#xD;
      will collect tissue and blood sample for exploratory analysis, including PD-L1 stuatus, tumor&#xD;
      mutation burden, et al.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 1, 2018</start_date>
  <completion_date type="Actual">December 31, 2020</completion_date>
  <primary_completion_date type="Actual">December 31, 2020</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>
    <intervention_model_description>PD-1 antibody, SHR-1210</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Response rate</measure>
    <time_frame>From first patient first visit to 6 month after last patient first visit ] Based on Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1)</time_frame>
    <description>The percentage of patients whose cancer shrinks or disappears after treatment</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression-Free Survival (PFS)</measure>
    <time_frame>up to approximately 1 year</time_frame>
    <description>PFS as measured in accordance with the Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>up to approximately 2 year</time_frame>
    <description>The time from registration to death due to any cause, or censored at date last known alive.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease Control Rate (DCR)</measure>
    <time_frame>From first patient first visit to 6 month after last patient first visit</time_frame>
    <description>Based on Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1)</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">6</enrollment>
  <condition>Gastric Cancer Stage IV</condition>
  <condition>EBV</condition>
  <arm_group>
    <arm_group_label>PD-1 antibody</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>SHR-1210, 200mg, ivdrip, d1, every two weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>PD-1 antibody (SHR-1210)</intervention_name>
    <description>PD-1 antibody (SHR-1210), 200mg, ivdrip, every 2 weeks.</description>
    <arm_group_label>PD-1 antibody</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Histologically confirmed Recurrent/Metastatic gastric adenocarcinoma;&#xD;
&#xD;
          2. EBER positive;&#xD;
&#xD;
          3. Failed from first-line platinum and fluorouracil based chemotherapy and second-line&#xD;
             chemotherapy; or could not tolerate systematic chemotherapy&#xD;
&#xD;
          4. ECOG performance status of 0 or 1;&#xD;
&#xD;
          5. Life expectancy ≥ 12 weeks;&#xD;
&#xD;
          6. Subjects must have measurable disease by CT or MRI per RECIST 1.1 criteria;&#xD;
&#xD;
          7. Can provide either a newly obtained or archival tumor tissue sample;&#xD;
&#xD;
          8. Adequate laboratory parameters during the screening period as evidenced by the&#xD;
             following:&#xD;
&#xD;
             Absolute neutrophil count ≥ 1.5 × 10^9/L ; Platelets ≥ 90 × 10^9/L; Hemoglobin ≥ 9.0&#xD;
             g/dL; Serum albumin ≥ 2.8g/dL; Total bilirubin (TBIL) ≤ 1.5 × upper limit of normal&#xD;
             (ULN), ALT and AST ≤ 1.5×ULN Creatinine clearance≥50 mL/min;&#xD;
&#xD;
          9. Female of child bearing potential, a negative urine or serum pregnancy test result&#xD;
             within 72 h before study treatment. Participants of reproductive potential must be&#xD;
             willing to use adequate contraception for the course of the study through 60 days&#xD;
             after the last dose of SHR-1210. Male subjects must be willing to use adequate&#xD;
             contraception for the course of the study through 120 days after the last dose of&#xD;
             SHR-1210;&#xD;
&#xD;
         10. Subjects must be willing to participate in the research and sign an informed consent&#xD;
             form (ICF);&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Subjects with any active autoimmune disease or history of autoimmune disease;&#xD;
&#xD;
          2. Subjects having clinical symptoms of metastases to central nervous system (such as&#xD;
             cerebral edema, requiring steroids intervention, or brain metastasis progression);&#xD;
&#xD;
          3. Has a known additional malignancy within the last 5 years before study treatment with&#xD;
             the exception of curatively treated basal cell and squamous cell carcinoma of the skin&#xD;
             and/or curatively resected in-situ cervical cancers;&#xD;
&#xD;
          4. Uncontrolled clinically significant heart disease, including but not limited to the&#xD;
             following: (1) &gt; NYHA II congestive heart failure; (2) unstable angina, (3) myocardial&#xD;
             infarction within the past 1 year; (4) clinically significant supraventricular&#xD;
             arrhythmia or ventricular arrhythmia requirement for treatment or intervention;&#xD;
&#xD;
          5. Concurrent medical condition requiring the use of cortisol (&gt;10mg/day Prednisone or&#xD;
             equivalent dose) or other systematic immunosuppressive medications within 14 days&#xD;
             before the study treatment. Except: inhalation or topical corticosteroids. Doses &gt; 10&#xD;
             mg/day prednisone or equivalent for replacement therapy;&#xD;
&#xD;
          6. Has received prior anti-cancer monoclonal antibody (mAb), chemotherapy, targeted small&#xD;
             molecule therapy within 4 weeks prior to first dosing or not recovered to ≤CTCAE 1&#xD;
             from adverse events (except for hair loss or neurotoxic sequelae from prior platinum&#xD;
             therapy) due to a previously administered agent. 7. Palliative irradiation finished&#xD;
             within 2 weeks;&#xD;
&#xD;
        8. Active infection or an unexplained fever &gt; 38.5°C before two weeks of first dosing&#xD;
        (subjects with tumor fever may be enrolled at the discretion of the investigator); 9. Known&#xD;
        Human Immunodeficiency Virus (HIV) infection、active Hepatitis B or Hepatitis C; 10.&#xD;
        Currently participating or has participated in a study within 4 weeks of the first dose of&#xD;
        study medication; 11. Pregnancy or breast feeding; 12. Prior therapy with a PD-1,&#xD;
        anti-PD-Ligand 1 (PD-L1) or CTLA-4 agent; 13. Subjects are known to have a history of&#xD;
        psychiatric substance abuse, alcoholism, or drug addiction; 14. According to the&#xD;
        investigator, other conditions that may lead to stop the research.&#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>Rui-Hua Xu, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Sun Yat-sen University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Cancer center of Sun Yat-sen University</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <zip>510060</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <results_reference>
    <citation>Sun YT, Guan WL, Zhao Q, Wang DS, Lu SX, He CY, Chen SZ, Wang FH, Li YH, Zhou ZW, Xu RH, Qiu MZ. PD-1 antibody camrelizumab for Epstein-Barr virus-positive metastatic gastric cancer: a single-arm, open-label, phase 2 trial. Am J Cancer Res. 2021 Oct 15;11(10):5006-5015. eCollection 2021.</citation>
    <PMID>34765307</PMID>
  </results_reference>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>November 22, 2018</study_first_submitted>
  <study_first_submitted_qc>November 26, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 28, 2018</study_first_posted>
  <last_update_submitted>September 16, 2022</last_update_submitted>
  <last_update_submitted_qc>September 16, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 21, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Sun Yat-sen University</investigator_affiliation>
    <investigator_full_name>Ruihua Xu</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>EBV</keyword>
  <keyword>Gatric cancer</keyword>
  <keyword>Check point inhibitor</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>Antibodies</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/NCT03755440
org study id: EBVaGC-SYSUCC
nct id: NCT03755440
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
EBV positive tumor accounts for 8-9% of all gastric cancer (GC) patients. PD-1 antibody has
      been proved as third line therapy for PD-L1 positive gastric cancer. Previous studies showed
      that EBV(+) tumors exhibit high response to PD-1 antibody. In this phase II study, we will
      investigate the efficacy and safety of PD-1 antibody in EBV positive metastatic GC patients.
EBV positive metastatic GC patients who failed to standard chemotherapy will receive therapy
      of single agent, PD-1 antibody, SHR-1210, 200mg, every 2 weeks. The primary endpoint is
      response rate. Secondary endpoint is progress free survival, overall survival, safety and
      quality of life. Using the Simon two-stage sample size calculation, the sample size is 19. We
      will collect tissue and blood sample for exploratory analysis, including PD-L1 stuatus, tumor
      mutation burden, et al.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: PD-1 antibody, SHR-1210
primary purpose: Treatment
masking: None (Open Label)
measure: Response rate
time frame: From first patient first visit to 6 month after last patient first visit ] Based on Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1)
description: The percentage of patients whose cancer shrinks or disappears after treatment
measure: Progression-Free Survival (PFS)
time frame: up to approximately 1 year
description: PFS as measured in accordance with the Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1
measure: Overall Survival (OS)
time frame: up to approximately 2 year
description: The time from registration to death due to any cause, or censored at date last known alive.
measure: Disease Control Rate (DCR)
time frame: From first patient first visit to 6 month after last patient first visit
description: Based on Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1)
arm group label: PD-1 antibody
arm group type: Experimental
description: SHR-1210, 200mg, ivdrip, d1, every two weeks.
intervention type: Drug
intervention name: PD-1 antibody (SHR-1210)
description: PD-1 antibody (SHR-1210), 200mg, ivdrip, every 2 weeks.
arm group label: PD-1 antibody
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Rui-Hua Xu, MD, PhD
role: Principal Investigator
affiliation: Sun Yat-sen University
facility: 
country: China
citation: Sun YT, Guan WL, Zhao Q, Wang DS, Lu SX, He CY, Chen SZ, Wang FH, Li YH, Zhou ZW, Xu RH, Qiu MZ. PD-1 antibody camrelizumab for Epstein-Barr virus-positive metastatic gastric cancer: a single-arm, open-label, phase 2 trial. Am J Cancer Res. 2021 Oct 15;11(10):5006-5015. eCollection 2021.
PMID: 34765307
responsible party type: Principal Investigator
investigator affiliation: Sun Yat-sen University
investigator full name: Ruihua Xu
investigator title: Professor
mesh term: Stomach Neoplasms
mesh term: Antibodies
sharing ipd: Undecided