xml: <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/NCT05970627</url>
    </required_header>
    <id_info>
      <org_study_id>IIT20230033C-R1</org_study_id>
      <nct_id>NCT05970627</nct_id>
    </id_info>
    <brief_title>Perioperative Chemotherapy Plus Toripalimab for Epstein-Barr Virus-associated Locally Advanced Gastric or Esophagogastric Junction Adenocarcinoma</brief_title>
    <official_title>Perioperative Chemotherapy Combined With PD-1 Inhibitor (Toripalimab) for Treatment of Epstein-Barr Virus-associated Locally Advanced Gastric or Esophagogastric Junction Adenocarcinoma: a Prospective, Multi-center, Phase II Study</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Yu jiren</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>First Affiliated Hospital of Zhejiang University</source>
    <oversight_info>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        This study is a prospective, single arm, multi-center phase II clinical trial designed to&#xD;
        evaluate the efficacy and safety of perioperative SOX combined with toripalimab in&#xD;
        participants with Epstein-Barr Virus-associated locally advanced gastric or esophagogastric&#xD;
        junction adenocarcinoma.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">July 28, 2023</start_date>
    <completion_date type="Anticipated">July 28, 2029</completion_date>
    <primary_completion_date type="Anticipated">July 28, 2026</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>Rate of pathological complete responses (pCR)</measure>
      <time_frame>From enrollment to surgery after pre-operative treatment (up to approximately 36 months)</time_frame>
      <description>Percentage of patients with pCR referring to the total number of enrolled and eligible patients, as evaluated centrally by a reference pathologist.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Overall survival</measure>
      <time_frame>From randomization to the last follow-up or death from any cause (up to approximately 72 months)</time_frame>
      <description>The duration of overall survival (OS) will be determined by measuring the time interval from enrollment to the end of follow up or death from any cause</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Progression-free survival</measure>
      <time_frame>From randomization to the last follow-up or the time of disease progression or relapse or death from any cause (up to approximately 72 months)</time_frame>
      <description>Progression-free survival (PFS) was defined as the time from randomization to the last follow-up or the time of disease progression or relapse or death from any cause.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>The incidences and types of adverse events (AE) and severe adverse events (SAE)</measure>
      <time_frame>From enrollment to 90-day after the last dose administration (up to approximately 39 months)</time_frame>
      <description>The incidences and severity of adverse events that occur during treatment will be evaluated according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.3</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">30</enrollment>
    <condition>Adenocarcinoma of the Stomach</condition>
    <condition>Adenocarcinoma of Esophagogastric Junction</condition>
    <condition>Epstein-Barr Virus-Associated Gastric Carcinoma</condition>
    <arm_group>
      <arm_group_label>Chemotherapy+Toripalimab</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Toripalimab: 240 mg IV infusion on Day 1 of each 21 day cycle for 3 cycles prior to surgery and 3 cycles after surgery.&#xD;
  Chemotherapy: SOX(S-1+Oxaliplatin) Oxaliplatin,administered as a 2-hour intravenous infusion (130mg/m2) S-1, orally twice daily for 2 weeks followed by a 7-day rest period. The dose of S-1 was 80 mg/day for body surface area less than 1.25 m2, 100 mg/day for body surface area greater than or equal to 1.25 to less than 1.5 m2, and 120 mg/day for body surface area greater than or equal to 1.5 m2 Chemotherapy will be repeated each 21 day for 3 cycles prior to surgery and 3 cycles after surgery.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Toripalimab</intervention_name>
      <description>Perioperative Toripalimab, 240 mg IV infusion</description>
      <arm_group_label>Chemotherapy+Toripalimab</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Oxaliplatin</intervention_name>
      <description>Oxaliplatin (130 mg/m2) infusion as perioperative chemotherapy</description>
      <arm_group_label>Chemotherapy+Toripalimab</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>S1</intervention_name>
      <description>S-1 orally intake as perioperative chemotherapy</description>
      <arm_group_label>Chemotherapy+Toripalimab</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Voluntary participation in the clinical study; fully understands and is informed of&#xD;
               the study and has signed the Informed Consent Form (ICF).&#xD;
  &#xD;
            2. Participants were ambulatory male or female. Age: ≥ 18 years and ≤ 80 years old.&#xD;
  &#xD;
            3. Histopathologically confirmed gastric or esophagogastric junction adenocarcinoma.&#xD;
  &#xD;
            4. Epstein-Barr Virus-associated Gastric or Esophagogastric Junction Adenocarcinoma,&#xD;
               which was determined by in situ hybridization (ISH) test of endoscopic biopsy&#xD;
               specimen.&#xD;
  &#xD;
            5. cT2-4bN+/-, M0 according to the American Joint Committee on Cancer and Union for&#xD;
               International Cancer Control (AJCC-UICC) TNM classification for carcinoma of the&#xD;
               stomach (8th edition).&#xD;
  &#xD;
            6. Participants had Eastern Cooperative Oncology Group (ECOG) performance status scores&#xD;
               of 0-1 within 7 days before the first dose of study treatment.&#xD;
  &#xD;
            7. Life expectancy ≥ 6 months.&#xD;
  &#xD;
            8. Agreement of providing baseline and surgical specimens for biomarker analysis.&#xD;
  &#xD;
            9. The functions of the vital organs meet requirements as follows (within 14 days before&#xD;
               the first dose of study treatment, meanwhile, participants had not received treatment&#xD;
               of recombinant human thrombopoietin or granulocyte stimulating factor):&#xD;
  &#xD;
          1). Hematological function&#xD;
  &#xD;
            -  White blood cell count (WBC): 3.5 × 10^9/L ~12.0 × 10^9/L&#xD;
  &#xD;
            -  Absolute neutrophil count (ANC) ≥ 1.5 × 10^9/L&#xD;
  &#xD;
            -  Platelet count (PLT) ≥ 100 × 10^9/L&#xD;
  &#xD;
            -  Hemoglobin (Hb) ≥ 90g/L. 2). Hepatic function&#xD;
  &#xD;
                 -  Total bilirubin (TBIL) ≤ 1.5 × ULN (upper limit of normal); -Aspartate&#xD;
                    aminotransferase (AST) ≤ 2.5 × ULN;&#xD;
  &#xD;
                 -  Alanine aminotransferase (ALT) ≤ 2.5 × ULN;&#xD;
  &#xD;
                 -  Albumin (ALB) ≥ 30g/L. 3). Renal function&#xD;
  &#xD;
                 -  Creatinine (Cr) ≤ 1.5 × ULN, or creatinine clearance ≥ 60 ml/min for those with&#xD;
                    creatinine level &gt; 1.5 × ULN.&#xD;
  &#xD;
                    4). Coagulation function&#xD;
  &#xD;
                 -  International normalized ratio (INR) ≤ 1.5;&#xD;
  &#xD;
                 -  Prothrombin time (PT) and activated partial thromboplastin time (APTT) ≤ 1.5 ×&#xD;
                    ULN.&#xD;
  &#xD;
                    10. Female participants of childbearing age must meet requirements: urine or&#xD;
                    serum pregnancy test must be negative within 7 days before the first dose of&#xD;
                    study treatment, and she must agree to use adequate contraception methods or keep&#xD;
                    abstinence (starting with the ICF is signed through 120 days after the last dose&#xD;
                    of toripalimab, or 180 days after the last dose of chemotherapy, whichever is&#xD;
                    longer, and should not be breastfeeding. Male participants must meet&#xD;
                    requirements: agree to use adequate contraception methods or keep abstinence&#xD;
                    (starting with the ICF is signed through 120 days after the last dose of&#xD;
                    toripalimab, or 180 days after the last dose of chemotherapy, whichever is&#xD;
                    longer).&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. HER2-positive status defined as either IHC score of 3+ or IHC 2+ with amplification&#xD;
               proven by fluorescent in situ hybridization (FISH) based on pretreatment endoscopic&#xD;
               biopsies.&#xD;
  &#xD;
            2. Prior systemic therapy for treatment of gastric cancer (surgery, chemotherapy,&#xD;
               radiotherapy, targeted therapy or immunotherapy).&#xD;
  &#xD;
            3. Previous or concurrent have other active malignant tumors within the past 5 years&#xD;
               (except for basal cell or squamous cell carcinoma of the skin, superficial bladder&#xD;
               cancer, prostate cancer or cervical cancer or breast cancer in situ that has undergone&#xD;
               curative therapy).&#xD;
  &#xD;
            4. Participants with gastric outlet obstruction, or unable to oral take, or severe&#xD;
               gastrointestinal bleeding.&#xD;
  &#xD;
            5. Myocardial infarction within 6 months before the first dose of study treatment,&#xD;
               uncontrolled angina, arrhythmia which need medical intervention (including but not&#xD;
               limited to cardiac pacemaker), congestive heart failure (New York Heart Association&#xD;
               (NYHA) class III or IV).&#xD;
  &#xD;
            6. Existence of chronic diarrhea (watery diarrhea: ≥ 5 times per day).&#xD;
  &#xD;
            7. Participants with active infection within 14 days before the first dose of study&#xD;
               treatment which need medical intervention.&#xD;
  &#xD;
            8. Participants with active tuberculosis.&#xD;
  &#xD;
            9. Previous or concurrent diagnosed with interstitial lung disease by imaging or&#xD;
               symptoms.&#xD;
  &#xD;
           10. Any of the following test is positive: Human Immunodeficiency Virus (HIV) antibody,&#xD;
               Hepatitis B surface Antigen (HBsAg), or Hepatitis C Virus (HCV) antibody.&#xD;
  &#xD;
           11. Participants who need long-term systemic steroid therapy (&gt; 10 mg/d prednisone&#xD;
               equivalent) or any other form of immunosuppressive therapy within 14 days before the&#xD;
               first dose of study treatment or during the study period.&#xD;
  &#xD;
           12. Concurrent or previous have severe allergic reaction to any antibody based drugs.&#xD;
  &#xD;
           13. Existence of any concurrent autoimmune disease, excepting participants with diabetes&#xD;
               mellitus type I, hypothyroidism requiring only hormone replacement therapy.&#xD;
  &#xD;
           14. Receive live vaccines within 28 days before the first dose of study treatment or&#xD;
               during the study period, excepting inactivated viral vaccines for seasonal influenza.&#xD;
  &#xD;
           15. Known history of allogeneic organ transplantation and allogeneic hematopoietic stem&#xD;
               cell transplantation.&#xD;
  &#xD;
           16. Existence of systemic disease that is difficult to control despite treatment with&#xD;
               several agents, for example, diabetes mellitus, hypertension, etc.&#xD;
  &#xD;
           17. Existence of other serious physical or mental diseases or serious laboratory&#xD;
               abnormalities that may increase the risk of participating in the study. Participants&#xD;
               who were judged unsuitable as subjects of this trial by investigator.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>80 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Jiren Yu</last_name>
      <role>Principal Investigator</role>
      <affiliation>First Affiliated Hospital of Zhejiang University</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Jiren Yu</last_name>
      <phone>0086-0571-87237931</phone>
      <email>yujr0909@zju.edu.cn</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Kankai Zhu</last_name>
      <email>zhukankai0401@163.com</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>The First Affiliated Hospital, College of Medicine, Zhejiang University</name>
        <address>
          <city>Hangzhou</city>
          <state>Zhejiang</state>
          <zip>310003</zip>
          <country>China</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>The Second Affiliated Hospital, College of Medicine, Zhejiang University</name>
        <address>
          <city>Hangzhou</city>
          <state>Zhejiang</state>
          <zip>310003</zip>
          <country>China</country>
        </address>
      </facility>
      <contact>
        <last_name>Jian Chen</last_name>
      </contact>
    </location>
    <location>
      <facility>
        <name>Huzhou Central Hospital</name>
        <address>
          <city>Huzhou</city>
          <state>Zhejiang</state>
          <zip>313099</zip>
          <country>China</country>
        </address>
      </facility>
      <contact>
        <last_name>Yunhai Wei</last_name>
      </contact>
    </location>
    <location>
      <facility>
        <name>Lishui Central Hospital</name>
        <address>
          <city>Lishui</city>
          <state>Zhejiang</state>
          <zip>323000</zip>
          <country>China</country>
        </address>
      </facility>
      <contact>
        <last_name>Hongtao Xu</last_name>
      </contact>
    </location>
    <location>
      <facility>
        <name>Ningbo First Hospital</name>
        <address>
          <city>Ningbo</city>
          <state>Zhejiang</state>
          <zip>315010</zip>
          <country>China</country>
        </address>
      </facility>
      <contact>
        <last_name>Zhilong Yan</last_name>
      </contact>
    </location>
    <location>
      <facility>
        <name>Ningbo Medical Center LiHuiLi Hospital</name>
        <address>
          <city>Ningbo</city>
          <state>Zhejiang</state>
          <zip>315048</zip>
          <country>China</country>
        </address>
      </facility>
      <contact>
        <last_name>Weiming Yu</last_name>
      </contact>
    </location>
    <location>
      <facility>
        <name>Ningbo Second Hospital</name>
        <address>
          <city>Ningbo</city>
          <state>Zhejiang</state>
          <zip>315099</zip>
          <country>China</country>
        </address>
      </facility>
      <contact>
        <last_name>Ping Chen</last_name>
      </contact>
    </location>
    <location>
      <facility>
        <name>Taizhou Hospital</name>
        <address>
          <city>Taizhou</city>
          <state>Zhejiang</state>
          <zip>317099</zip>
          <country>China</country>
        </address>
      </facility>
      <contact>
        <last_name>Shenkang Zhou</last_name>
      </contact>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>July 25, 2023</study_first_submitted>
    <study_first_submitted_qc>July 25, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 1, 2023</study_first_posted>
    <last_update_submitted>July 25, 2023</last_update_submitted>
    <last_update_submitted_qc>July 25, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 1, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor-Investigator</responsible_party_type>
      <investigator_affiliation>First Affiliated Hospital of Zhejiang University</investigator_affiliation>
      <investigator_full_name>Yu jiren</investigator_full_name>
      <investigator_title>Director of gastrointestinal surgery department</investigator_title>
    </responsible_party>
    <keyword>Gastric Adenocarcinoma</keyword>
    <keyword>Esophagogastric Junction Adenocarcinoma</keyword>
    <keyword>Perioperative Chemotherapy</keyword>
    <keyword>Toripalimab</keyword>
    <keyword>Epstein-Barr Virus-associated gastric cancer</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Epstein-Barr Virus Infections</mesh_term>
      <mesh_term>Adenocarcinoma</mesh_term>
      <mesh_term>Stomach Neoplasms</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Oxaliplatin</mesh_term>
    </intervention_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05970627
  org study id: IIT20230033C-R1
  nct id: NCT05970627
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  This study is a prospective, single arm, multi-center phase II clinical trial designed to
        evaluate the efficacy and safety of perioperative SOX combined with toripalimab in
        participants with Epstein-Barr Virus-associated locally advanced gastric or esophagogastric
        junction adenocarcinoma.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Rate of pathological complete responses (pCR)
  time frame: From enrollment to surgery after pre-operative treatment (up to approximately 36 months)
  description: Percentage of patients with pCR referring to the total number of enrolled and eligible patients, as evaluated centrally by a reference pathologist.
  measure: Overall survival
  time frame: From randomization to the last follow-up or death from any cause (up to approximately 72 months)
  description: The duration of overall survival (OS) will be determined by measuring the time interval from enrollment to the end of follow up or death from any cause
  measure: Progression-free survival
  time frame: From randomization to the last follow-up or the time of disease progression or relapse or death from any cause (up to approximately 72 months)
  description: Progression-free survival (PFS) was defined as the time from randomization to the last follow-up or the time of disease progression or relapse or death from any cause.
  measure: The incidences and types of adverse events (AE) and severe adverse events (SAE)
  time frame: From enrollment to 90-day after the last dose administration (up to approximately 39 months)
  description: The incidences and severity of adverse events that occur during treatment will be evaluated according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.3
  arm group label: Chemotherapy+Toripalimab
  arm group type: Experimental
  description: Toripalimab: 240 mg IV infusion on Day 1 of each 21 day cycle for 3 cycles prior to surgery and 3 cycles after surgery.
  Chemotherapy: SOX(S-1+Oxaliplatin) Oxaliplatin,administered as a 2-hour intravenous infusion (130mg/m2) S-1, orally twice daily for 2 weeks followed by a 7-day rest period. The dose of S-1 was 80 mg/day for body surface area less than 1.25 m2, 100 mg/day for body surface area greater than or equal to 1.25 to less than 1.5 m2, and 120 mg/day for body surface area greater than or equal to 1.5 m2 Chemotherapy will be repeated each 21 day for 3 cycles prior to surgery and 3 cycles after surgery.
  intervention type: Drug
  intervention name: Toripalimab
  description: Perioperative Toripalimab, 240 mg IV infusion
  arm group label: Chemotherapy+Toripalimab
  intervention type: Drug
  intervention name: Oxaliplatin
  description: Oxaliplatin (130 mg/m2) infusion as perioperative chemotherapy
  arm group label: Chemotherapy+Toripalimab
  intervention type: Drug
  intervention name: S1
  description: S-1 orally intake as perioperative chemotherapy
  arm group label: Chemotherapy+Toripalimab
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 80 Years
  healthy volunteers: No
  last name: Jiren Yu
  role: Principal Investigator
  affiliation: First Affiliated Hospital of Zhejiang University
  last name: Jiren Yu
  phone: 0086-0571-87237931
  email: yujr0909@zju.edu.cn
  last name: Kankai Zhu
  email: zhukankai0401@163.com
  facility: 
  facility: 
  contact: 
  facility: 
  contact: 
  facility: 
  contact: 
  facility: 
  contact: 
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  contact: 
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  country: China
  responsible party type: Sponsor-Investigator
  investigator affiliation: First Affiliated Hospital of Zhejiang University
  investigator full name: Yu jiren
  investigator title: Director of gastrointestinal surgery department
  mesh term: Epstein-Barr Virus Infections
  mesh term: Adenocarcinoma
  mesh term: Stomach Neoplasms
  mesh term: Oxaliplatin