<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/NCT03765775</url>
  </required_header>
  <id_info>
    <org_study_id>LC01</org_study_id>
    <nct_id>NCT03765775</nct_id>
  </id_info>
  <brief_title>Anlotinib Plus Sintilimab for NSCLC Patients With First-generation EGFR-TKIs Drug Resistance Along With T790M Negative</brief_title>
  <official_title>A Randomized, Phase II Study of Anlotinib Combined With Sintilimab(IBI 308) in First-generation EGFR-TKIs Drug Resistance Along With T790M Negative NSCLC</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>First Hospital of Shijiazhuang City</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>First Hospital of Shijiazhuang City</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 an efficacy and safety study of Anlotinib combined with Sintilimab (IBI 308) in&#xD;
      participants with advanced or metastatic non-small cell lung cancer (NSCLC) who have received&#xD;
      first-generation EGFR-TKIs resistance along with T790M negative.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Participants receive Sintilimab(IBI 308) 200 mg, administered as intravenous (IV) infusion on&#xD;
      Day 1, Anlotinib 12mg, administered as PO on Day1-14 of each 21-day cycle until documented&#xD;
      PD.The primary hypothesis of this study is that participants will have a longer Progression&#xD;
      Free Survival (PFS), as assessed by Response Evaluation Criteria in Solid Tumors version 1.1&#xD;
      (RECIST 1.1) when treated with Anlotinib plus Sintilimab(IBI 308).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">November 20, 2018</start_date>
  <completion_date type="Anticipated">December 31, 2021</completion_date>
  <primary_completion_date type="Anticipated">December 31, 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>Progression-Free Survival (PFS)</measure>
    <time_frame>6 months</time_frame>
    <description>PFS was defined as the time from randomization to documented disease progression per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) or death due to any cause, whichever occurred first and was based on blinded independent central radiologists' (BICR) review. Progressive Disease (PD) was defined as ≥20% increase in the sum of diameters of target lesions and an absolute increase of ≥5 mm. (Note: the appearance of one or more new lesions was also considered progression). Participants were evaluated every 9 weeks with radiographic imaging to assess their response to treatment.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Over Survival(OS)</measure>
    <time_frame>2years</time_frame>
    <description>OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the analysis were censored at the date of the last follow-up. In those instances where participants were confirmed to be alive on the visit cut-off date of 09 May 2016, survival was censored as of 09 May 2016.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate (ORR)</measure>
    <time_frame>2yeas</time_frame>
    <description>ORR was defined as the percentage of participants in the analysis population who experienced a Complete Response (CR; disappearance of all target lesions) or a Partial Response (PR; at least a 30% decrease in the sum of diameters of target lesions) and was assessed using RECIST 1.1 based on BICR evaluation.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Carcinoma</condition>
  <condition>Non-small Cell Lung Cancer</condition>
  <condition>Lung Neoplasm</condition>
  <arm_group>
    <arm_group_label>Anlotinib Hydrochloride+Sintilimab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants receive Sintilimab (IBI 308) 200 mg, administered as intravenous (IV) infusion on Day 1 of each 21-day cycle , Anlotinib 12mg, administered as PO on Day1-14 of each 21-day cycle until documented PD</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Sintilimab</intervention_name>
    <description>Participants receive Sintilimab(IBI 308) 200 mg, administered as intravenous (IV) infusion on Day 1 of each 21-day cycle</description>
    <arm_group_label>Anlotinib Hydrochloride+Sintilimab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Anlotinib Hydrochloride</intervention_name>
    <description>Participants receive Anlotinib 10 mg, administered as PO on Day 1-14 of each 21-day cycle</description>
    <arm_group_label>Anlotinib Hydrochloride+Sintilimab</arm_group_label>
    <other_name>Anlotinib</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. The subjects volunteered to participate in this study and signed the informed consent&#xD;
             form, with good compliance and follow-up.&#xD;
&#xD;
          2. Male or female patients aged 18-75 years old.&#xD;
&#xD;
          3. Has a histologically-confirmed or cytologically confirmed diagnosis of stage IV&#xD;
             nonsquamous NSCLC.&#xD;
&#xD;
             Has confirmation that epidermal growth factor receptor (EGFR) mutation，with&#xD;
             first-generation EGFR-TKIs drug resistance T790M negative .&#xD;
&#xD;
          4. Has measurable disease.&#xD;
&#xD;
          5. There is at least one target lesion that has not received radiotherapy in the past 3&#xD;
             months, and it can be accurately measured in at least one direction (the maximum&#xD;
             diameter needs to be recorded) by magnetic resonance imaging (MRI) or computed&#xD;
             tomography (CT), in which conventional CT is greater than 20mm or spiral CT is greater&#xD;
             than 10mm.&#xD;
&#xD;
          6. Has a life expectancy of at least 3 months.&#xD;
&#xD;
          7. Has a performance status of 0 or 2 on the Eastern Cooperative Oncology Group (ECOG)&#xD;
             Performance Status.&#xD;
&#xD;
          8. Has adequate organ function.&#xD;
&#xD;
          9. Patients with asymptomatic or mild brain metastasis may be enrolled.&#xD;
&#xD;
         10. If female of childbearing potential, is willing to use adequate contraception for the&#xD;
             course of the study through 120 days after the last dose of study medication or&#xD;
             through 180 days after last dose of chemotherapeutic agents.&#xD;
&#xD;
         11. If male with a female partner(s) of child-bearing potential, must agree to use&#xD;
             adequate contraception starting with the first dose of study medication through 120&#xD;
             days after the last dose of study medication or through 180 days after last dose of&#xD;
             chemotherapeutic agents.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        1. Squamous cell carcinoma (including adenosquamous carcinoma);Small cell lung cancer&#xD;
        (including small cell cancer and non-small cell mixed lung cancer).&#xD;
&#xD;
        2.ALK(Anaplastic Lymphoma kinase) positive. 3.Imaging (CT or MRI) showed that the tumor&#xD;
        lesion invaded the central tumor of local large blood vessels;Or there is obvious pulmonary&#xD;
        cavitation or necrotic tumor.&#xD;
&#xD;
        4.History and complications&#xD;
&#xD;
          1. Has known active central nervous system (CNS) metastases and/or carcinomatous&#xD;
             meningitis.(patients with brain metastasis who have completed treatment 14 days before&#xD;
             enrollment and have stable symptoms can be included in the group, but they need to be&#xD;
             confirmed as having no symptoms of cerebral hemorrhage by brain MRI, CT).&#xD;
&#xD;
          2. Have Participated in other clinical studies or less than 4 weeks before the end of&#xD;
             treatment in the previous clinical study.&#xD;
&#xD;
          3. Other active malignancies requiring concurrent treatment.&#xD;
&#xD;
          4. Known history of prior malignancy except if participant has undergone potentially&#xD;
             curative therapy with no evidence of that disease recurrence for 5 years since&#xD;
             initiation of that therapy, except for successful definitive resection of basal cell&#xD;
             carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the&#xD;
             skin, in situ cervical cancer, or other in situ cancers.&#xD;
&#xD;
          5. Patients who have not recovered to level 1 or lower of NCI-CTCAE4.0 （The Common&#xD;
             Terminology Criteria for Adverse Events 4.0）after previous systemic anti-tumor&#xD;
             treatment with anti-tumor treatment-related adverse reactions (except hair loss).&#xD;
&#xD;
          6. Abnormal coagulation function (INR(international normalized ratio) &gt;1.5 or&#xD;
             PT(prothrombin time) &gt; ULN+4 s or APTT(activated partial thromboplastin time ) &gt;&#xD;
             1.5ULN), with bleeding tendency or receiving thrombolytic or anticoagulant treatment.&#xD;
&#xD;
          7. Is expected to require any other form of antineoplastic therapy while on study.&#xD;
&#xD;
          8. Received a live-virus vaccination within 30 days of planned start of study medication.&#xD;
&#xD;
          9. Known sensitivity to any component of Anlotinib or Sintilimab.&#xD;
&#xD;
         10. Has active autoimmune disease that has required systemic treatment in past 2 years.&#xD;
&#xD;
         11. Is on chronic systemic steroids.&#xD;
&#xD;
         12. Has an active infection requiring therapy.&#xD;
&#xD;
         13. Has known history of Human Immunodeficiency Virus (HIV).&#xD;
&#xD;
         14. Has known active Hepatitis B or C.&#xD;
&#xD;
         15. Has known psychiatric or substance abuse disorder that would interfere with&#xD;
             cooperation with the requirements of the trial.&#xD;
&#xD;
         16. Is a regular user (including &quot;recreational use&quot;) of any illicit drugs or had a recent&#xD;
             history (within the last year) of substance abuse (including alcohol).&#xD;
&#xD;
         17. Has symptomatic ascites or pleural effusion.&#xD;
&#xD;
         18. Has interstitial lung disease or a history of pneumonitis that required oral of IV&#xD;
             glucocorticoids to assist with management.&#xD;
&#xD;
         19. Two or more combination therapies for hypertension that are still uncontrollable&#xD;
             (systolic blood pressure greater than 140 mmHg or diastolic blood pressure greater&#xD;
             than 90 mmHg).&#xD;
&#xD;
         20. Arteriovenous thrombosis events occurred within 12 months before enrollment, such as&#xD;
             cerebrovascular accidents (including temporary ischemic attack, cerebral hemorrhage,&#xD;
             cerebral infarction), deep vein thrombosis and pulmonary embolism.&#xD;
&#xD;
         21. clinically significant hemoptysis occurred within 3 months before enrollment&#xD;
             (hemoptysis &gt; 50ml daily);Or bleeding symptoms of significant clinical significance or&#xD;
             with a clear bleeding tendency, such as gastrointestinal bleeding, bleeding gastric&#xD;
             ulcer, baseline stool occult blood ++ or above, or suffering from vasculitis.&#xD;
&#xD;
         22. factors that significantly affect oral drug absorption, such as inability to swallow,&#xD;
             chronic diarrhea and intestinal obstruction.&#xD;
&#xD;
         23. Is pregnant or breastfeeding, or expecting to conceive or father children prior to 120&#xD;
             days after the last dose of study medication or through 180 days after last dose of&#xD;
             chemotherapeutic agents.&#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>Yan Zhang, M.D.</last_name>
    <role>Study Chair</role>
    <affiliation>The First Hospital of Shijiazhuang</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Yan Zhang, M.D.</last_name>
    <phone>17603119607</phone>
    <phone_ext>+86</phone_ext>
    <email>13315978836@163.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>The First Hospital of Shijiazhuang</name>
      <address>
        <city>Shijiazhuang</city>
        <state>Hebei</state>
        <zip>050011</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Yan Zhang</last_name>
      <phone>17603119607</phone>
      <phone_ext>+86</phone_ext>
      <email>13315978836@163.com</email>
    </contact>
    <contact_backup>
      <last_name>Yanan Duan</last_name>
      <phone>15931106929</phone>
      <phone_ext>+86</phone_ext>
      <email>yanan2006@sohu.com</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>December 2018</verification_date>
  <study_first_submitted>December 4, 2018</study_first_submitted>
  <study_first_submitted_qc>December 4, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 5, 2018</study_first_posted>
  <last_update_submitted>December 5, 2018</last_update_submitted>
  <last_update_submitted_qc>December 5, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">December 6, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Non-small Cell Lung Cancer</keyword>
  <keyword>Anlotinib</keyword>
  <keyword>Sintilimab</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>
  <!-- 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/NCT03765775
org study id: LC01
nct id: NCT03765775
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This is an efficacy and safety study of Anlotinib combined with Sintilimab (IBI 308) in
      participants with advanced or metastatic non-small cell lung cancer (NSCLC) who have received
      first-generation EGFR-TKIs resistance along with T790M negative.
Participants receive Sintilimab(IBI 308) 200 mg, administered as intravenous (IV) infusion on
      Day 1, Anlotinib 12mg, administered as PO on Day1-14 of each 21-day cycle until documented
      PD.The primary hypothesis of this study is that participants will have a longer Progression
      Free Survival (PFS), as assessed by Response Evaluation Criteria in Solid Tumors version 1.1
      (RECIST 1.1) when treated with Anlotinib plus Sintilimab(IBI 308).
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Progression-Free Survival (PFS)
time frame: 6 months
description: PFS was defined as the time from randomization to documented disease progression per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) or death due to any cause, whichever occurred first and was based on blinded independent central radiologists' (BICR) review. Progressive Disease (PD) was defined as ≥20% increase in the sum of diameters of target lesions and an absolute increase of ≥5 mm. (Note: the appearance of one or more new lesions was also considered progression). Participants were evaluated every 9 weeks with radiographic imaging to assess their response to treatment.
measure: Over Survival(OS)
time frame: 2years
description: OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the analysis were censored at the date of the last follow-up. In those instances where participants were confirmed to be alive on the visit cut-off date of 09 May 2016, survival was censored as of 09 May 2016.
measure: Objective Response Rate (ORR)
time frame: 2yeas
description: ORR was defined as the percentage of participants in the analysis population who experienced a Complete Response (CR; disappearance of all target lesions) or a Partial Response (PR; at least a 30% decrease in the sum of diameters of target lesions) and was assessed using RECIST 1.1 based on BICR evaluation.
arm group label: Anlotinib Hydrochloride+Sintilimab
arm group type: Experimental
description: Participants receive Sintilimab (IBI 308) 200 mg, administered as intravenous (IV) infusion on Day 1 of each 21-day cycle , Anlotinib 12mg, administered as PO on Day1-14 of each 21-day cycle until documented PD
intervention type: Biological
intervention name: Sintilimab
description: Participants receive Sintilimab(IBI 308) 200 mg, administered as intravenous (IV) infusion on Day 1 of each 21-day cycle
arm group label: Anlotinib Hydrochloride+Sintilimab
intervention type: Drug
intervention name: Anlotinib Hydrochloride
description: Participants receive Anlotinib 10 mg, administered as PO on Day 1-14 of each 21-day cycle
arm group label: Anlotinib Hydrochloride+Sintilimab
other name: Anlotinib
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Yan Zhang, M.D.
role: Study Chair
affiliation: The First Hospital of Shijiazhuang
last name: Yan Zhang, M.D.
phone: 17603119607
phone ext: +86
email: 13315978836@163.com
facility: 
status: Recruiting
contact: 
contact backup: 
country: China
responsible party type: Sponsor
mesh term: Lung Neoplasms
mesh term: Carcinoma, Non-Small-Cell Lung