<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/NCT03830411</url>
  </required_header>
  <id_info>
    <org_study_id>CTGU002</org_study_id>
    <nct_id>NCT03830411</nct_id>
  </id_info>
  <brief_title>A Study of Sintilimab Compared With Docetaxel or Pemetrexed as Second-line Treatment for Patients With Stage IV Nonsquamous Non-small Cell Lung Cancer After Failure With Platinum-Containing Chemotherapy</brief_title>
  <official_title>A Phase II, Prospective, Single-center, Randomized, Controlled Study to Investigate the Efficacy and Safety of Sintilimab Compared With Docetaxel or Pemetrexed as Second-line Treatment for Patients With Stage IV Nonsquamous Non-small Cell Lung Cancer With Wild-type EGFR After Failure With Platinum-Containing Chemotherapy.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Xin-Hua Xu</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>China Three Gorges University, Yichang, China</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 prospective, single-center, randomized, controlled study will evaluate the efficacy and&#xD;
      safety of sintilimab compared with docetaxel or pemetrexed as second-line treatment for&#xD;
      patients with stage IV nonsquamous non-small cell lung cancer with wild-type EGFR after&#xD;
      failure with platinum-containing chemotherapy. Treatment may continue as long as participants&#xD;
      are experiencing clinical benefit as assessed by the investigator, i.e., in the absence of&#xD;
      unacceptable toxicity or symptomatic deterioration attributed to disease progression.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">March 13, 2019</start_date>
  <completion_date type="Anticipated">June 30, 2022</completion_date>
  <primary_completion_date type="Anticipated">June 30, 2022</primary_completion_date>
  <phase>Phase 2</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)</measure>
    <time_frame>Approximately 21 months</time_frame>
    <description>Overall Survival (OS) was defined as the time from the date of randomization to the date of death due to any cause. Data for participants who were not reported as dead at the time of analysis was censored at the date when they were last known to be alive.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate (ORR)</measure>
    <time_frame>Approximately 21 months</time_frame>
    <description>ORR was defined as the percentage of participants with confirmed objective tumor response, complete response (CR) or partial response (PR), as determined by investigator using RECIST v1.1 criteria.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival (PFS)</measure>
    <time_frame>Approximately 21 months</time_frame>
    <description>PFS was defined as the time between the date of randomization and the date of first documented disease progression or death, whichever occurs first. Disease progression was determined based on investigator assessment using response evaluation criteria In solid tumors (RECIST) v1.1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response (DOR)</measure>
    <time_frame>Approximately 21 months</time_frame>
    <description>DOR was defined as the duration from the first tumor assessment that supports the participant's objective response (CR or PR, whichever is first recorded) to disease progression or death due to any cause, whichever occurs first.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Emergence of adverse events(AEs)</measure>
    <time_frame>Approximately 21 months</time_frame>
    <description>AEs graded using CTCAE (Version 4.0) criteria.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">76</enrollment>
  <condition>Nonsquamous Non-Small Cell Lung Cancer</condition>
  <arm_group>
    <arm_group_label>Arm A: Sintilimab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive Sintilimab as long as they continue to experience clinical benefit in the opinion of the investigator until unacceptable toxicity or symptomatic deterioration attributed to disease progression as determined by the investigator.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm B: Chemotherapy (Docetaxel or Pemetrexed)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants randomized to the chemotherapy arm will receive docetaxel or pemetrexed until disease progression per standard RECIST v1.1 or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sintilimab</intervention_name>
    <description>Sintilimab will be administered intravenously at a fixed dose of 200 milligrams (mg) on Day 1 of each 21-day cycle.</description>
    <arm_group_label>Arm A: Sintilimab</arm_group_label>
    <other_name>IBI308</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Docetaxel</intervention_name>
    <description>Docetaxel 75 milligrams per square meter (mg/m^2) will be administered intravenously on Day 1 of each 21-day cycle.</description>
    <arm_group_label>Arm B: Chemotherapy (Docetaxel or Pemetrexed)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pemetrexed</intervention_name>
    <description>Pemetrexed 500 mg/m^2 will be administered intravenously on Day 1 of each 21-day cycle.</description>
    <arm_group_label>Arm B: Chemotherapy (Docetaxel or Pemetrexed)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Volunteer to participate in clinical research; fully understand and know the research&#xD;
             and sign informed consent;&#xD;
&#xD;
          2. Age ≥ 18 years old and ≤ 75 years old, either sex;&#xD;
&#xD;
          3. Eastern Collaborative Oncology Group Performance status (ECOG PS) 0, 1 or 2;&#xD;
&#xD;
          4. Has a histologically or cytologically confirmed diagnosis of stage IV (according to&#xD;
             the 8th edition of the International Association for the Study of Lung Cancer)&#xD;
             nonsquamous NSCLC;&#xD;
&#xD;
          5. Have at least one measurable lesion as defined by RECIST 1.1;&#xD;
&#xD;
          6. Has progression of disease after treatment with at least two cycles of a&#xD;
             platinum-containing doublet chemotherapy according to RECIST V.1.1;&#xD;
&#xD;
          7. Patients without activating EGFR mutation;&#xD;
&#xD;
          8. Normal hepatic function: total bilirubin≤1.5×normal upper limit (ULN); Alanine&#xD;
             aminotransferase and Aspartate aminotransferase levels ≤2.5×ULN or ≤5×ULN if liver&#xD;
             metastasis is present;&#xD;
&#xD;
          9. Normal renal function: Creatinine ≤1.5×ULN or calculated creatinine clearance ≥45&#xD;
             mL/min (using Cockcroft/Gault formula to calculate );&#xD;
&#xD;
         10. Normal hematological function: absolute neutrophil count ≥1.5×109/L, platelet count&#xD;
             ≥70×109/L, hemoglobin≥80g/L [no blood transfusion or erythropoietin (EPO) within 7&#xD;
             days] Dependency];&#xD;
&#xD;
         11. Has a life expectancy of at ≥3 months.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. ECOG PS &gt;2;&#xD;
&#xD;
          2. Small cell lung cancer and squamous NSCLC;&#xD;
&#xD;
          3. EGFR mutation or mutation status unknown;&#xD;
&#xD;
          4. Known hypersensitivity or allergy to monoclonal antibody;&#xD;
&#xD;
          5. Prior therapy with an anti-programmed cell death (PD)-1, anti-PD-L1, anti-PD-L2,&#xD;
             anti-tumor necrosis factor CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4&#xD;
             (CTLA-4) antibody (including any other antibody or drug specifically targeting T-cell&#xD;
             co-stimulation or checkpoint pathways);&#xD;
&#xD;
          6. Active autoimmune disease, or a documented history of autoimmune disease;&#xD;
&#xD;
          7. Treatment with systemic corticosteroids (prednisone≥10mg per day or equivalent dose)&#xD;
             or other systemic immunosuppressive medications within 2 weeks prior to the first&#xD;
             dose;&#xD;
&#xD;
          8. Known history or active human immunodeficiency virus (HIV);&#xD;
&#xD;
          9. Known acute or chronic active hepatitis B (HBV DNA positive) infection or acute or&#xD;
             chronic active hepatitis C (HCV antibody positive and HCV RNA positive) infection;&#xD;
&#xD;
         10. Interstitial lung disease, or history of pneumonitis requiring systemic steroids for&#xD;
             treatment;&#xD;
&#xD;
         11. Active or poorly controlled severe infection;&#xD;
&#xD;
         12. Have serious cardiovascular disease: Symptomatic congestive heart failure (New York&#xD;
             Heart Association grade III-IV), unstable angina pectoris, unstable arrhythmia,&#xD;
             myocardial infarction or cerebrovascular accident within 3 months before&#xD;
             randomization;&#xD;
&#xD;
         13. Received thoracic radiation therapy of &gt;30 Gy within 6 months prior to first dose of&#xD;
             study drug;&#xD;
&#xD;
         14. Completed palliative radiotherapy within 7 days prior to first dose of study drug;&#xD;
&#xD;
         15. Pregnant or lactating women.&#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_contact>
    <last_name>Xinhua Xu, Master</last_name>
    <phone>+8613986747496</phone>
    <phone_ext>+8613986747496</phone_ext>
    <email>2732774352@qq.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Yan Wang, Master</last_name>
    <phone>+8615997550081</phone>
    <phone_ext>+8615997550081</phone_ext>
    <email>wangyan82033@163.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Department of Medical Oncology, Central Hospital of Yichang City, the First Clinical Medical College of Three Gorges University</name>
      <address>
        <city>Yichang</city>
        <state>Hubei</state>
        <zip>443003</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Xinhua Xu</last_name>
      <phone>+8613986747496</phone>
      <phone_ext>+8613986747496</phone_ext>
      <email>2732774352@qq.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>November 2021</verification_date>
  <study_first_submitted>February 2, 2019</study_first_submitted>
  <study_first_submitted_qc>February 2, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 5, 2019</study_first_posted>
  <last_update_submitted>November 5, 2021</last_update_submitted>
  <last_update_submitted_qc>November 5, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">November 8, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>China Three Gorges University, Yichang, China</investigator_affiliation>
    <investigator_full_name>Xin-Hua Xu</investigator_full_name>
    <investigator_title>professor</investigator_title>
  </responsible_party>
  <keyword>Sintilimab</keyword>
  <keyword>docetaxel</keyword>
  <keyword>pemetrexed</keyword>
  <keyword>nonsquamous non-small-cell lung cancer</keyword>
  <keyword>wild-type EGFR</keyword>
  <keyword>second-line treatment</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Non-Small-Cell Lung</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Docetaxel</mesh_term>
    <mesh_term>Pemetrexed</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/NCT03830411
org study id: CTGU002
nct id: NCT03830411
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This prospective, single-center, randomized, controlled study will evaluate the efficacy and
      safety of sintilimab compared with docetaxel or pemetrexed as second-line treatment for
      patients with stage IV nonsquamous non-small cell lung cancer with wild-type EGFR after
      failure with platinum-containing chemotherapy. Treatment may continue as long as participants
      are experiencing clinical benefit as assessed by the investigator, i.e., in the absence of
      unacceptable toxicity or symptomatic deterioration attributed to disease progression.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Overall Survival (OS)
time frame: Approximately 21 months
description: Overall Survival (OS) was defined as the time from the date of randomization to the date of death due to any cause. Data for participants who were not reported as dead at the time of analysis was censored at the date when they were last known to be alive.
measure: Objective Response Rate (ORR)
time frame: Approximately 21 months
description: ORR was defined as the percentage of participants with confirmed objective tumor response, complete response (CR) or partial response (PR), as determined by investigator using RECIST v1.1 criteria.
measure: Progression-free survival (PFS)
time frame: Approximately 21 months
description: PFS was defined as the time between the date of randomization and the date of first documented disease progression or death, whichever occurs first. Disease progression was determined based on investigator assessment using response evaluation criteria In solid tumors (RECIST) v1.1.
measure: Duration of response (DOR)
time frame: Approximately 21 months
description: DOR was defined as the duration from the first tumor assessment that supports the participant's objective response (CR or PR, whichever is first recorded) to disease progression or death due to any cause, whichever occurs first.
measure: Emergence of adverse events(AEs)
time frame: Approximately 21 months
description: AEs graded using CTCAE (Version 4.0) criteria.
arm group label: Arm A: Sintilimab
arm group type: Experimental
description: Participants will receive Sintilimab as long as they continue to experience clinical benefit in the opinion of the investigator until unacceptable toxicity or symptomatic deterioration attributed to disease progression as determined by the investigator.
arm group label: Arm B: Chemotherapy (Docetaxel or Pemetrexed)
arm group type: Active Comparator
description: Participants randomized to the chemotherapy arm will receive docetaxel or pemetrexed until disease progression per standard RECIST v1.1 or unacceptable toxicity.
intervention type: Drug
intervention name: Sintilimab
description: Sintilimab will be administered intravenously at a fixed dose of 200 milligrams (mg) on Day 1 of each 21-day cycle.
arm group label: Arm A: Sintilimab
other name: IBI308
intervention type: Drug
intervention name: Docetaxel
description: Docetaxel 75 milligrams per square meter (mg/m^2) will be administered intravenously on Day 1 of each 21-day cycle.
arm group label: Arm B: Chemotherapy (Docetaxel or Pemetrexed)
intervention type: Drug
intervention name: Pemetrexed
description: Pemetrexed 500 mg/m^2 will be administered intravenously on Day 1 of each 21-day cycle.
arm group label: Arm B: Chemotherapy (Docetaxel or Pemetrexed)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Xinhua Xu, Master
phone: +8613986747496
phone ext: +8613986747496
email: 2732774352@qq.com
last name: Yan Wang, Master
phone: +8615997550081
phone ext: +8615997550081
email: wangyan82033@163.com
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Sponsor-Investigator
investigator affiliation: China Three Gorges University, Yichang, China
investigator full name: Xin-Hua Xu
investigator title: professor
mesh term: Lung Neoplasms
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Docetaxel
mesh term: Pemetrexed
sharing ipd: No