<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/NCT03811054</url>
  </required_header>
  <id_info>
    <org_study_id>BeijingCH002</org_study_id>
    <nct_id>NCT03811054</nct_id>
  </id_info>
  <brief_title>The Efficacy and Drug Resistance Molecular Biology of Apatinib Combined With EGFR-TK1 Treated for Advanced Slow-progressed Non-Small Cell Lung Cancer (NSCLC)</brief_title>
  <official_title>The Efficacy and Drug Resistance Molecular Biology of Apatinib Combined With EGFR-TK1 Treated for Advanced Slow-progressed Non-Small Cell Lung Cancer (NSCLC)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Beijing Chest Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Beijing Chest Hospital</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>
      Patients with advanced non-small cell lung cancer (NSCLC) who progress slowly after Epidermal&#xD;
      Growth Factor Receptor Tyrosine Kinase Inhibitors（EGFR-TKI）resistance. The purpose of this&#xD;
      study is to investigate the efficacy and drug resistance mechanism of Apatinib combine with&#xD;
      EGFR-TK1 treated for advanced slow progressed non-small cell lung cancer and provide new&#xD;
      treatment options.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Epidermal growth factor receptor Tyrosine kinase inhibitor (EGFR TKI) have been approved to&#xD;
      treat NSCLC harboring EGFR mutation as first-line therapy. However, a large proportion of&#xD;
      patients would become acquired resistant of EGFR-TKI after about one year although initially&#xD;
      sensitivity. Previous studies demonstrated that the anti-angiogenesis combined with EGFR-TKI&#xD;
      in slow-progressed EGFR mutation-positive non-small cell lung cancer achieved good efficacy&#xD;
      and disease control rates, prolonged the progression free survival. The present study is aim&#xD;
      to expand the number of samples to monitor resistance-related genes and tumor cells.&#xD;
      Furthermore, to investigate the mechanism of anti-angiogenesis combine with EGFR-TKI and&#xD;
      provide the theory for the use and promotion of clinically protocols. In this study, the&#xD;
      primary objective is the objective response rates and the secondary goal are disease control&#xD;
      rates, overall survival, progression free survival and drug safety.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">December 1, 2018</start_date>
  <completion_date type="Anticipated">December 2020</completion_date>
  <primary_completion_date type="Anticipated">December 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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Objective response rates (ORR)</measure>
    <time_frame>two years</time_frame>
    <description>Objective response rate is defined as the percentage of subjects having achieved confirmed Complete Response + Partial Response according to Response Evaluation Criteria in Solid Tumors 1.1（RECIST1.1）</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Disease control rate (DCR)</measure>
    <time_frame>two years</time_frame>
    <description>Disease Control Rate is defined as the percentage of subjects having achieved confirmed Complete Response + Partial Response + Stable Disease according to radiological assessments.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>two years</time_frame>
    <description>Time from randomization to death for any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival (PFS)</measure>
    <time_frame>two years</time_frame>
    <description>PFS defined as date of randomization until the date of objectively determined progression defined by Response Evaluation Criteria in Solid Tumors criteria or death from any cause, whichever is first.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Drug safety: Number of participants with treatment-related adverse events</measure>
    <time_frame>two years</time_frame>
    <description>Number of participants with treatment-related adverse events as assessed by CTCAE v4.0</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Non Small Cell Lung Cancer</condition>
  <arm_group>
    <arm_group_label>Apatinib combined with EGFR-TKI</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Apatinib 250 millgram（mg/day（d））combined with EGFR-TKI</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Apatinib（250mg/d） combined with EGFR-TKI</intervention_name>
    <description>Patients with advanced non-small cell lung cancer (NSCLC) who had treated with EGFR-TKI and progressed slowly because of resistance are underwent with apatinib mesylate and continuous EGFR-TKI.</description>
    <arm_group_label>Apatinib combined with EGFR-TKI</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Informed consent should be obtained before treatment. Patients with good compliance.&#xD;
&#xD;
          2. Histologically or cytologically confirmed IIIB/IV NSCLC.&#xD;
&#xD;
          3. Progress in the treatment of EGFR TKI.&#xD;
&#xD;
          4. Aged from 18 to 75 years (18 and 75 years are included); Gender Not Required.&#xD;
&#xD;
          5. ECOG PS 0-1.&#xD;
&#xD;
          6. Life expectancy ≥ 3 months.&#xD;
&#xD;
          7. At least one measurable lesion (meet the requirements of the standard Response&#xD;
             Evaluation Criteria In Solid Tumors (RESCIST) version 1.1). If the lesions that have&#xD;
             received local treatment (radiation, radiofrequency, intervention, etc.) are the only&#xD;
             lesions, it is required to have clear imaging progress.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Uncontrolled hypertension (systolic ≥140mmHg and/or diastolic ≥90mmHg after medication&#xD;
             treatment); Poor control of blood sugar.&#xD;
&#xD;
          2. Acute phase of cerebral infarction, or recovery period &lt;2 months.&#xD;
&#xD;
          3. A variety of factors that affect the absorption of oral medications (such as inability&#xD;
             to swallow, nausea and vomiting, chronic diarrhea, intestinal obstruction, etc.)&#xD;
&#xD;
          4. Patients with a risk of gastrointestinal bleeding may not be enrolled, including the&#xD;
             following: (1) active digestive ulcer lesions, and fecal occult blood (++); (2) a&#xD;
             history of melena and hematemesis within 2 months. Simple fecal occult blood (+) is&#xD;
             not an exclusion criterion.&#xD;
&#xD;
          5. Coagulation abnormality (INR&gt;1.5×ULN, APTT&gt;1.5×ULN), with bleeding tendency.&#xD;
&#xD;
          6. Urine protein ≥ ++ or confirmed 24-hour urine protein quantitation &gt; 1.0 g.&#xD;
&#xD;
          7. Pregnant or lactating women.&#xD;
&#xD;
          8. Severe liver and kidney dysfunction (grade 4) .&#xD;
&#xD;
          9. Allergic to any ingredient of apatinib mesylate.&#xD;
&#xD;
         10. A history of abuse of psychotropic substances and are unable to quit smoking or mental&#xD;
             disorders.&#xD;
&#xD;
         11. According to the investigator's judgment, people with concomitant diseases that&#xD;
             seriously endanger the safety of the patient or affect the patient's completion of the&#xD;
             study.&#xD;
&#xD;
         12. Surgery, major trauma or fracture, within 4 weeks before the treatment or unhealed&#xD;
             wound before treatment.&#xD;
&#xD;
         13. Severe heart disease, such as grade III or above (NYHA standard) congestive heart&#xD;
             failure, grade III or above (CCS standard) angina, a history of myocardial infarction&#xD;
             within 6 months before the treatment, or medication treated arrhythmia.&#xD;
&#xD;
         14. Brain metastasis and meningeal metastasis.&#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>Liyan Xu, MD</last_name>
    <phone>86-89509157</phone>
    <email>xuliyan2009@yahoo.cn</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Jing Liu</last_name>
    <phone>86-89509157</phone>
  </overall_contact_backup>
  <location>
    <facility>
      <name>The Beijing Chest Hospital</name>
      <address>
        <city>Beijing</city>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Liyan Xu, MD</last_name>
      <email>xuliyan2009@yahoo.cn</email>
    </contact>
    <investigator>
      <last_name>Liyan Xu, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>January 14, 2019</study_first_submitted>
  <study_first_submitted_qc>January 18, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 22, 2019</study_first_posted>
  <last_update_submitted>January 18, 2019</last_update_submitted>
  <last_update_submitted_qc>January 18, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 22, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Beijing Chest Hospital</investigator_affiliation>
    <investigator_full_name>Liyan Xu</investigator_full_name>
    <investigator_title>Chief of Medical Oncology Department</investigator_title>
  </responsible_party>
  <keyword>Apatinib</keyword>
  <keyword>Non Small Cell Lung Cancer</keyword>
  <keyword>EGFR TKI</keyword>
  <keyword>slowly progress</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>Apatinib</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/NCT03811054
org study id: BeijingCH002
nct id: NCT03811054
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Patients with advanced non-small cell lung cancer (NSCLC) who progress slowly after Epidermal
      Growth Factor Receptor Tyrosine Kinase Inhibitors（EGFR-TKI）resistance. The purpose of this
      study is to investigate the efficacy and drug resistance mechanism of Apatinib combine with
      EGFR-TK1 treated for advanced slow progressed non-small cell lung cancer and provide new
      treatment options.
Epidermal growth factor receptor Tyrosine kinase inhibitor (EGFR TKI) have been approved to
      treat NSCLC harboring EGFR mutation as first-line therapy. However, a large proportion of
      patients would become acquired resistant of EGFR-TKI after about one year although initially
      sensitivity. Previous studies demonstrated that the anti-angiogenesis combined with EGFR-TKI
      in slow-progressed EGFR mutation-positive non-small cell lung cancer achieved good efficacy
      and disease control rates, prolonged the progression free survival. The present study is aim
      to expand the number of samples to monitor resistance-related genes and tumor cells.
      Furthermore, to investigate the mechanism of anti-angiogenesis combine with EGFR-TKI and
      provide the theory for the use and promotion of clinically protocols. In this study, the
      primary objective is the objective response rates and the secondary goal are disease control
      rates, overall survival, progression free survival and drug safety.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Objective response rates (ORR)
time frame: two years
description: Objective response rate is defined as the percentage of subjects having achieved confirmed Complete Response + Partial Response according to Response Evaluation Criteria in Solid Tumors 1.1（RECIST1.1）
measure: Disease control rate (DCR)
time frame: two years
description: Disease Control Rate is defined as the percentage of subjects having achieved confirmed Complete Response + Partial Response + Stable Disease according to radiological assessments.
measure: Overall survival (OS)
time frame: two years
description: Time from randomization to death for any cause.
measure: Progression free survival (PFS)
time frame: two years
description: PFS defined as date of randomization until the date of objectively determined progression defined by Response Evaluation Criteria in Solid Tumors criteria or death from any cause, whichever is first.
measure: Drug safety: Number of participants with treatment-related adverse events
time frame: two years
description: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
arm group label: Apatinib combined with EGFR-TKI
arm group type: Experimental
description: Apatinib 250 millgram（mg/day（d））combined with EGFR-TKI
intervention type: Drug
intervention name: Apatinib（250mg/d） combined with EGFR-TKI
description: Patients with advanced non-small cell lung cancer (NSCLC) who had treated with EGFR-TKI and progressed slowly because of resistance are underwent with apatinib mesylate and continuous EGFR-TKI.
arm group label: Apatinib combined with EGFR-TKI
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Liyan Xu, MD
phone: 86-89509157
email: xuliyan2009@yahoo.cn
last name: Jing Liu
phone: 86-89509157
facility: 
status: Recruiting
contact: 
investigator: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Beijing Chest Hospital
investigator full name: Liyan Xu
investigator title: Chief of Medical Oncology Department
mesh term: Lung Neoplasms
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Apatinib