<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/NCT03758677</url>
  </required_header>
  <id_info>
    <org_study_id>K2018095</org_study_id>
    <nct_id>NCT03758677</nct_id>
  </id_info>
  <brief_title>Apatinib Combined With Chemotherapy for NSCLC Patients Without T790M Mutation</brief_title>
  <official_title>A Prospective, Single-center, One-arm Clinical Study of Apatinib Combined With Chemotherapy for Patients Who Progressed After First Line EGFR-TKI Treatment Without T790M Mutation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The First Hospital of Jilin University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>The First Hospital of Jilin 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>
      At present, with the increasing intensities of the tobacco industry and air pollution in&#xD;
      China, the incidence and mortality of lung cancer have become the most important issue that&#xD;
      threatens human health.Over the past two decades, the treatment of EGFR+ NSCLC is molecular&#xD;
      target therapy (EGFR-TKI). However, only about 30 percent patients with T790M mutation could&#xD;
      accept 3rd generation of EGFR-TKI（AZD9291) , most of the patients with progressive disease&#xD;
      statuses still stays in the mode of treatment based on radiotherapy and chemotherapy. This is&#xD;
      a prospective, single-center, one-arm clinical study designed to evaluate the efficacy and&#xD;
      safety of apatinib plus chemotherapy for 30 patients who progressed after EGFR-TKI treatment&#xD;
      without T790M mutation. The participants will receive apatinib 250mg qd orally combine with&#xD;
      chemotherapy, if the patient has a grade 3/4 adverse reaction during such treatment, it can&#xD;
      be reduced to apatinib 250mg orally once per two days. Chemotherapeutic agents are limited to&#xD;
      platinum-based double drugs chemotherapy.The primary outcome endpoint was progression-free&#xD;
      survival.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">August 1, 2020</start_date>
  <completion_date type="Anticipated">November 20, 2021</completion_date>
  <primary_completion_date type="Anticipated">November 20, 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>PFS</measure>
    <time_frame>One to two years</time_frame>
    <description>Progression-free survival</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>OS</measure>
    <time_frame>Five years</time_frame>
    <description>Overall survival</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AEs</measure>
    <time_frame>One year</time_frame>
    <description>Adverse events</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>DCR</measure>
    <time_frame>One year</time_frame>
    <description>Disease control rate</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ORR</measure>
    <time_frame>One year</time_frame>
    <description>Objective response rate</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Non Small Cell Lung Cancer</condition>
  <arm_group>
    <arm_group_label>Patients who progressed after EGFR-TKI without T790M mutation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single arm; Plan to enroll 30 cases; Patients who progressed after EGFR-TKI treatment without T790M mutation</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Apatinib</intervention_name>
    <description>30 patients who progressed after EGFR-TKI treatment without T790M mutation will receive apatinib 250mg qd orally combine with chemotherapy , if the patient has a grade 3/4 adverse reaction during such treatment, apatinib should be reduced to 250mg orally once per two days. Chemotherapeutic agents are limited to platinum-based double drugs(Pemetrexed,Gemcitabine,Docetaxel).</description>
    <arm_group_label>Patients who progressed after EGFR-TKI without T790M mutation</arm_group_label>
    <other_name>Chemotherapy with platinum-based double drugs(Pemetrexed,Gemcitabine,Docetaxel)</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        1. male or female patients: 18-75 years old; 2. ECOG performance status score: 0~2 points;&#xD;
        3. Non small cell lung cancer patients who progressed after first line EGFR -TKI treatment&#xD;
        without T790M mutation 4.Expected survival period ≥12 weeks; 5.The normal function of major&#xD;
        organs, that is, the relevant inspection indicators within the first 14 days of randomness,&#xD;
        meet the following requirements:&#xD;
&#xD;
          1. Blood tests:&#xD;
&#xD;
               1. Hemoglobin ≥ 90 g/L (without transfusion in 14 days);&#xD;
&#xD;
               2. Neutrophil count ≥ 1.5×109/L;&#xD;
&#xD;
               3. Platelet count ≥ 100×109/L;&#xD;
&#xD;
          2. Biochemical check:&#xD;
&#xD;
        a .total bilirubin ≤ 1.5 x ULN (upper limit of normal value); b.serum alanine&#xD;
        aminotransferase (ALT) or serum aspartate aminotransferase (AST) ≤ 2.5× ULN; if liver&#xD;
        metastases, ALT or AST ≤ 5 × ULN; c.Serum creatinine &lt; 1.5 times the upper limit of normal;&#xD;
        Endogenous creatinine clearance ≥ 50 ml/min (Cockcroft-Gault formula); 3) Assessment of&#xD;
        cardiac Doppler ultrasound: Left ventricular ejection fraction (LVEF) ≥ 50%.&#xD;
&#xD;
        6.Women of childbearing age must have a pregnancy test (serum or urine) within 7 days prior&#xD;
        to enrollment, and the result is negative, and they are willing to use appropriate methods&#xD;
        of contraception during the trial and within 8 weeks of the last administration of the test&#xD;
        drug. For males, consent must be given for contraception or surgical sterilization within 8&#xD;
        weeks of the test period and the last administration of the test drug; 7.Subjects have&#xD;
        completely healed after surgery and no bleeding tendency; 8.Good compliance, family members&#xD;
        agree to follow the survival follow- up; 9.Sign the informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        1. In the past or at the same time suffering from other malignant tumors, 2. Participated&#xD;
        in other drug clinical trials within four weeks; 3. Has a variety of factors that affect&#xD;
        oral medication (such as inability to swallow, chronic diarrhea, and intestinal&#xD;
        obstruction); 4. There is a history of bleeding, and any serious grading within 4 weeks&#xD;
        prior to screening has reached 3 degrees or more in CTCAE 4.0; 5. Pre-screening patients&#xD;
        with symptomatic central nervous system metastasis or history of central nervous system&#xD;
        metastasis; 6. People with high blood pressure who cannot be well controlled by single&#xD;
        antihypertensive drugs (systolic blood pressure &gt; 140 mmHg, diastolic blood pressure&gt; 90&#xD;
        mmHg); patients with a history of unstable angina; newly diagnosed angina in the first 3&#xD;
        months before screening or myocardial infarction within 6 months prior to screening;&#xD;
        arrhythmia (including QTcF: male ≥450 ms , ≥ 470 ms for females) long-term use of&#xD;
        antiarrhythmic drugs and New York Heart Association grade ≥ grade II cardiac insufficiency;&#xD;
        7. Urine prompts urinary protein ≥ ++ and confirmed 24-hour urinary protein quantification&gt;&#xD;
        1.0 g; 8. Combined with anastomotic leakage, duodenal stump fistula, pancreatic fistula or&#xD;
        anastomotic stenosis and other serious postoperative complications; 9. Long-term unhealed&#xD;
        wounds or incompletely-healed fractures; 10 . Imaging shows that the tumor has invaded an&#xD;
        important blood vessel or the investigator judged that the patient's tumor had a high risk&#xD;
        of invading vital blood vessels and causing fatal bleeding during treatment; 11. Abnormal&#xD;
        coagulation, bleeding tendency (14 days before randomization must meet: in the absence of&#xD;
        resistance In the case of coagulants, the INR is within the normal range; Patients treated&#xD;
        with anticoagulants or vitamin K antagonists such as warfarin, heparin, or the like;&#xD;
        International normalized ratio (INR) ≤ 1.5 for prothrombin time Under the premise that&#xD;
        small doses of warfarin (1 mg orally, once daily) or low dose aspirin (with daily dose not&#xD;
        exceeding 100 mg) are allowed for prophylactic purposes; 12. Incidence of&#xD;
        arteriovenous/venous thromboembolism within the first year of screening, such as&#xD;
        cerebrovascular accident (including transient ischemic attack), deep venous thrombosis&#xD;
        (except for venous thrombosis due to venous catheterization in previous chemotherapy) ) and&#xD;
        pulmonary embolism; 13. For female subjects: Surgical sterilization, postmenopausal&#xD;
        patients, or agree to use a medically approved contraceptive measure during study treatment&#xD;
        and within 6 months of the end of the study treatment period; prior to study enrollment&#xD;
        Serum or urine pregnancy tests must be negative within 7 days and must be non-lactating.&#xD;
        Male subjects: Should be surgically sterilized, or agree to use a medically-accepted&#xD;
        contraceptive treatment during study treatment and within 6 months of the end of the study&#xD;
        treatment period; 14. In the past,there was abnormal thyroid function. Even in the case of&#xD;
        drug therapy, thyroid function could not be maintained within the normal range.&#xD;
&#xD;
        15. Those who have a history of abuse of psychotropic substances and are unable to get rid&#xD;
        of or have mental disorders; 16. Has a history of immunodeficiency, or has other acquired,&#xD;
        congenital immunodeficiency disorders, or has a history of organ transplantation.&#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>Kewei Ma, PHD</last_name>
    <phone>0086-13756060506</phone>
    <email>makw@jlu.edu.cn</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Yinghui Xu, PHD</last_name>
    <phone>0086-13944826247</phone>
    <email>305682733@qq.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>The First Hospital of Jilin University</name>
      <address>
        <city>Changchun</city>
        <state>Jilin</state>
        <zip>130021</zip>
        <country>China</country>
      </address>
    </facility>
    <contact>
      <last_name>Kewei Ma</last_name>
      <phone>008613756060506</phone>
      <email>makw@jlu.edu.cn</email>
    </contact>
    <contact_backup>
      <last_name>Yinghui Xu</last_name>
      <phone>008613944826247</phone>
      <email>305682733@qq.com</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>November 28, 2018</study_first_submitted>
  <study_first_submitted_qc>November 28, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 29, 2018</study_first_posted>
  <last_update_submitted>July 21, 2020</last_update_submitted>
  <last_update_submitted_qc>July 21, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 23, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <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>Gemcitabine</mesh_term>
    <mesh_term>Docetaxel</mesh_term>
    <mesh_term>Pemetrexed</mesh_term>
    <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/NCT03758677
org study id: K2018095
nct id: NCT03758677
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
At present, with the increasing intensities of the tobacco industry and air pollution in
      China, the incidence and mortality of lung cancer have become the most important issue that
      threatens human health.Over the past two decades, the treatment of EGFR+ NSCLC is molecular
      target therapy (EGFR-TKI). However, only about 30 percent patients with T790M mutation could
      accept 3rd generation of EGFR-TKI（AZD9291) , most of the patients with progressive disease
      statuses still stays in the mode of treatment based on radiotherapy and chemotherapy. This is
      a prospective, single-center, one-arm clinical study designed to evaluate the efficacy and
      safety of apatinib plus chemotherapy for 30 patients who progressed after EGFR-TKI treatment
      without T790M mutation. The participants will receive apatinib 250mg qd orally combine with
      chemotherapy, if the patient has a grade 3/4 adverse reaction during such treatment, it can
      be reduced to apatinib 250mg orally once per two days. Chemotherapeutic agents are limited to
      platinum-based double drugs chemotherapy.The primary outcome endpoint was progression-free
      survival.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: PFS
time frame: One to two years
description: Progression-free survival
measure: OS
time frame: Five years
description: Overall survival
measure: AEs
time frame: One year
description: Adverse events
measure: DCR
time frame: One year
description: Disease control rate
measure: ORR
time frame: One year
description: Objective response rate
arm group label: Patients who progressed after EGFR-TKI without T790M mutation
arm group type: Experimental
description: Single arm; Plan to enroll 30 cases; Patients who progressed after EGFR-TKI treatment without T790M mutation
intervention type: Drug
intervention name: Apatinib
description: 30 patients who progressed after EGFR-TKI treatment without T790M mutation will receive apatinib 250mg qd orally combine with chemotherapy , if the patient has a grade 3/4 adverse reaction during such treatment, apatinib should be reduced to 250mg orally once per two days. Chemotherapeutic agents are limited to platinum-based double drugs(Pemetrexed,Gemcitabine,Docetaxel).
arm group label: Patients who progressed after EGFR-TKI without T790M mutation
other name: Chemotherapy with platinum-based double drugs(Pemetrexed,Gemcitabine,Docetaxel)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Kewei Ma, PHD
phone: 0086-13756060506
email: makw@jlu.edu.cn
last name: Yinghui Xu, PHD
phone: 0086-13944826247
email: 305682733@qq.com
facility: 
contact: 
contact backup: 
country: China
responsible party type: Sponsor
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Gemcitabine
mesh term: Docetaxel
mesh term: Pemetrexed
mesh term: Apatinib