<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/NCT03755115</url>
  </required_header>
  <id_info>
    <org_study_id>SHR-1210-EPI-II</org_study_id>
    <nct_id>NCT03755115</nct_id>
  </id_info>
  <brief_title>SHR-1210 Combined With Epirubicin in the Treatment of Extensive Disease Small Cell Lung Cancer</brief_title>
  <official_title>Clinical Study of PD-1 Monoclonal Antibody SHR-1210 Combined With Epirubicin in the Treatment of Extensive Small Cell Lung Cancer After First-line Treatment Failure</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Henan Cancer Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Jiangsu HengRui Medicine Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Henan Cancer Hospital</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>
      Patients with extensive disease SCLC after failure of first-line treatment were enrolled with&#xD;
      SHR-1210 and epirubicin for 3 cycles to evaluate initial efficacy&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Small cell lung cancer is a neuroendocrine tumor with strong invasiveness, rapid growth rate&#xD;
      and early metastasis in lung cancer. The systemic chemotherapy response rate is high in a&#xD;
      wide range of patients, but it is easy to resist drug recurrence, which brings certain&#xD;
      difficulties to clinical treatment. The signaling pathway activated by programmed cell death&#xD;
      receptor 1 (PD-1) and its ligand (programmed death-ligand 1, PDL1) is a hotspot in recent&#xD;
      years and has brought good news to cancer patients. However, PD1 inhibitors are only about&#xD;
      13% effective in treating lung cancer patients. Epirubicin is a classic drug that activates&#xD;
      the immunogenicity of tumor tissues, induces tumor immunogenic death, and releases some&#xD;
      marker proteins such as CRT, HMGB1, HSP and so on. These two drugs combine to enhance the&#xD;
      anti-tumor effect of the human immune system.The investigators designed the study to explore&#xD;
      the possibility of apatinib as the Second-line Therapy in ED-SCLC.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">February 1, 2019</start_date>
  <completion_date type="Anticipated">May 31, 2020</completion_date>
  <primary_completion_date type="Anticipated">October 28, 2019</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>ORR</measure>
    <time_frame>6 month</time_frame>
    <description>Objective Response Rate</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>PFS</measure>
    <time_frame>2 years</time_frame>
    <description>Progression Free Survival</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>DCR</measure>
    <time_frame>2 years</time_frame>
    <description>Disease Control Rate</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>OS</measure>
    <time_frame>2 years</time_frame>
    <description>Overall Survival</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AE</measure>
    <time_frame>2 year</time_frame>
    <description>Adverse reactions</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>characteristic antigen on the surface of immunogenic dead cells</measure>
    <time_frame>3 month</time_frame>
    <description>characteristic antigen on the surface of immunogenic dead cells,such as CRT(calnetulin),HSP(heat shock protein),HMGB1(High-mobility group box 1 protein),TIL (tumor infiltrating lymphocytes)，ATP,which are measured by IHC or ELISA.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">40</enrollment>
  <condition>Small Cell Lung Cancer Extensive Stage</condition>
  <arm_group>
    <arm_group_label>Epirubicin plus SHR1210</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>First intravenous injection of epirubicin injection, D1,30mg/m^2 Then intravenous administration with SHR-1210,D1, a fixed dose of 200mg, D1,30min per infusion, Q2W. The total dose of epirubicin is 360 mg/m^2.next SHR-1210 single drug maintenance .Until to secdonary disease progression or intolerance side effects.Evaluate efficacy every 3 cycles.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Epirubicin plus SHR1210</intervention_name>
    <description>First intravenous injection of epirubicin injection, D1,30mg/m^2 Then intravenous administration with SHR-1210,D1, a fixed dose of 200mg, 30min per infusion, Q2W. The total dose of epirubicin is 360 mg/m^2.next SHR-1210 single drug maintenance .Until to secdonary disease progression or intolerance side effects.Evaluate efficacy every 3 cycles.</description>
    <arm_group_label>Epirubicin plus SHR1210</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. The subject is 18-75 years old when the informed consent form is signed, and the&#xD;
             gender is not limited.&#xD;
&#xD;
          2. Histological or cytological diagnosis of patients with extensive small cell lung&#xD;
             cancer (ED-SCLC).&#xD;
&#xD;
          3. Must provide specimens of tumor tissue at or after diagnosis of advanced or metastatic&#xD;
             tumors or consent to biopsy, formalized or freshly obtained, formalin-fixed,&#xD;
             paraffin-embedded (FFPE) within 1 month prior to the first dose. After the tumor&#xD;
             tissue block can cut at least 10 slices for staining and detection.&#xD;
&#xD;
          4. Subjects have undergone rapid progression or relapse of drug resistance after&#xD;
             first-line treatment.&#xD;
&#xD;
          5. According to the RECIST 1.1 standard, subjects must have a target lesion that can be&#xD;
             measured by CT or MRI.&#xD;
&#xD;
        6, ECOG PS score: 0-1 points. 7. The expected survival period is ≥ 3 months. 8, the main&#xD;
        organ function meets the following criteria: a) blood routine (no blood transfusion within&#xD;
        14 days, no G-CSF, no use of drugs to correct): absolute neutrophil ≥ 1.5 × 109 / L,&#xD;
        platelets ≥ 100 × 109 / L, hemoglobin ≥ 90 g / L, white blood cells ≥ 4.0 × 109 / L and ≤&#xD;
        15 × 109 / L; b) blood biochemistry: total bilirubin ≤ 1.5 ULN, AST / ALT ≤ 2.5 ULN, (if&#xD;
        liver metastasis, then ≤ 5 times the upper limit of normal value), ALB ≥ 30 g / L, serum&#xD;
        creatinine ≤ 1.5 ULN; c) Coagulation function: APTT ≤ 1.5 × ULN and prothrombin time -&#xD;
        international normalized ratio (PT-INR) &lt; 1.5xULN ( Did not receive anticoagulant therapy).&#xD;
&#xD;
        9. Volunteer to participate in clinical trials and sign informed consent, good compliance&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        1. Target disease exclusion criteria: 1) Exclude subjects without measurable lesions 2)&#xD;
        Subjects who can be surgically resected or radically treated. 3) Subjects who have received&#xD;
        anti-PD-1 (L1) or CTLA4 mAb treatment.&#xD;
&#xD;
        History and comorbidities: 1) Exclude any active, known or suspected autoimmune disease in&#xD;
        the subject 2) Exclude 2, use anti-tumor vaccine or other anti-tumor with immune&#xD;
        stimulation within 1 month before the first dose Subjects treated with drugs. 3) Exclude&#xD;
        subjects who are highly suspected of having interstitial pneumonia. 4) Subjects who&#xD;
        excluded other active malignancies requiring simultaneous treatment excluded subjects with&#xD;
        grade II or higher myocardial ischemia or myocardial infarction, poorly controlled&#xD;
        arrhythmias, and grade III to IV cardiac insufficiency. 5) Exclude subjects with active&#xD;
        tuberculosis (TB). 6) Exclude subjects who had severe infections within 4 weeks prior to&#xD;
        the first dose. Exclude subjects with any active infection. 7) Exclude subjects who are&#xD;
        ready or have undergone tissue/organ transplantation. 8) Exclude subjects who have been&#xD;
        vaccinated or will be vaccinated within 30 days prior to the first dose.&#xD;
&#xD;
        3. Physical examination and laboratory examinations 1) A known history of human&#xD;
        immunodeficiency virus (HIV) is known or known to have acquired immunodeficiency syndrome&#xD;
        (AIDS). 2) Untreated active hepatitis. 3) Exclude subjects with uncontrolled pleural&#xD;
        effusion, pericardial effusion, or ascites requiring repeated drainage.&#xD;
&#xD;
        4, allergic reactions and adverse drug reactions 1) severe allergic reactions to other&#xD;
        monoclonal antibodies. 2) Allergic or intolerant to the infusion. 3) Serious intolerance to&#xD;
        epirubicin or toxicity.&#xD;
&#xD;
        5. Exclude subjects with mental illness, alcoholism, refrain from quitting, drug use or&#xD;
        substance abuse.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Tongde Tian</last_name>
    <role>Principal Investigator</role>
    <affiliation>Henan Cancer Hospital (The Affiliated Cancer Hospital of Zhengzhou University)</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Tongde Tian</last_name>
    <phone>0086-15093118217</phone>
    <email>tian_tong_de@163.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Du Yang</last_name>
    <phone>0086-18737704121</phone>
    <email>1061453586@qq.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Tian Tongde</name>
      <address>
        <city>Zhengzhou</city>
        <state>Henan</state>
        <zip>450000</zip>
        <country>China</country>
      </address>
    </facility>
    <contact>
      <last_name>Tongde Tian</last_name>
      <phone>0086+15093118217</phone>
      <email>tian_tong_de@163.com</email>
    </contact>
    <contact_backup>
      <last_name>Du Yang</last_name>
      <phone>0086+18737704121</phone>
      <email>1061453586@qq.com</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>November 2018</verification_date>
  <study_first_submitted>November 17, 2018</study_first_submitted>
  <study_first_submitted_qc>November 25, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 27, 2018</study_first_posted>
  <last_update_submitted>January 15, 2019</last_update_submitted>
  <last_update_submitted_qc>January 15, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 16, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>ICD</keyword>
  <keyword>PD1</keyword>
  <keyword>ED-SCLC</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Neoplasms</mesh_term>
    <mesh_term>Small Cell Lung Carcinoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Epirubicin</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03755115
org study id: SHR-1210-EPI-II
nct id: NCT03755115
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Patients with extensive disease SCLC after failure of first-line treatment were enrolled with
      SHR-1210 and epirubicin for 3 cycles to evaluate initial efficacy
Small cell lung cancer is a neuroendocrine tumor with strong invasiveness, rapid growth rate
      and early metastasis in lung cancer. The systemic chemotherapy response rate is high in a
      wide range of patients, but it is easy to resist drug recurrence, which brings certain
      difficulties to clinical treatment. The signaling pathway activated by programmed cell death
      receptor 1 (PD-1) and its ligand (programmed death-ligand 1, PDL1) is a hotspot in recent
      years and has brought good news to cancer patients. However, PD1 inhibitors are only about
      13% effective in treating lung cancer patients. Epirubicin is a classic drug that activates
      the immunogenicity of tumor tissues, induces tumor immunogenic death, and releases some
      marker proteins such as CRT, HMGB1, HSP and so on. These two drugs combine to enhance the
      anti-tumor effect of the human immune system.The investigators designed the study to explore
      the possibility of apatinib as the Second-line Therapy in ED-SCLC.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: ORR
time frame: 6 month
description: Objective Response Rate
measure: PFS
time frame: 2 years
description: Progression Free Survival
measure: DCR
time frame: 2 years
description: Disease Control Rate
measure: OS
time frame: 2 years
description: Overall Survival
measure: AE
time frame: 2 year
description: Adverse reactions
measure: characteristic antigen on the surface of immunogenic dead cells
time frame: 3 month
description: characteristic antigen on the surface of immunogenic dead cells,such as CRT(calnetulin),HSP(heat shock protein),HMGB1(High-mobility group box 1 protein),TIL (tumor infiltrating lymphocytes)，ATP,which are measured by IHC or ELISA.
arm group label: Epirubicin plus SHR1210
arm group type: Experimental
description: First intravenous injection of epirubicin injection, D1,30mg/m^2 Then intravenous administration with SHR-1210,D1, a fixed dose of 200mg, D1,30min per infusion, Q2W. The total dose of epirubicin is 360 mg/m^2.next SHR-1210 single drug maintenance .Until to secdonary disease progression or intolerance side effects.Evaluate efficacy every 3 cycles.
intervention type: Drug
intervention name: Epirubicin plus SHR1210
description: First intravenous injection of epirubicin injection, D1,30mg/m^2 Then intravenous administration with SHR-1210,D1, a fixed dose of 200mg, 30min per infusion, Q2W. The total dose of epirubicin is 360 mg/m^2.next SHR-1210 single drug maintenance .Until to secdonary disease progression or intolerance side effects.Evaluate efficacy every 3 cycles.
arm group label: Epirubicin plus SHR1210
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Tongde Tian
role: Principal Investigator
affiliation: Henan Cancer Hospital (The Affiliated Cancer Hospital of Zhengzhou University)
last name: Tongde Tian
phone: 0086-15093118217
email: tian_tong_de@163.com
last name: Du Yang
phone: 0086-18737704121
email: 1061453586@qq.com
facility: 
contact: 
contact backup: 
country: China
responsible party type: Sponsor
mesh term: Lung Neoplasms
mesh term: Small Cell Lung Carcinoma
mesh term: Epirubicin