<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/NCT03766490</url>
  </required_header>
  <id_info>
    <org_study_id>ALTER-L010</org_study_id>
    <nct_id>NCT03766490</nct_id>
  </id_info>
  <brief_title>Anlotinib Hydrochloride Combined With EGFR TKIs in Advanced Non-small Cell Lung Cancer</brief_title>
  <official_title>A Prospective, Single-arm, Multicenter Study of Anlotinib Hydrochloride Combined With First-generation EGFR TKIs as Second-line Treatment in Acquired (Non-T790M Mutation) Resistance Advanced Non-small Cell Lung Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The First Affiliated Hospital of Soochow University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>The First People's Hospital of Changzhou</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Second Affiliated Hospital of Soochow University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Nantong University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Affiliated Hospital of Jiangnan University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Jiangyin People's Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Changzhou No.2 People's Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Chia Tai Tianqing Pharmaceutical Group Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>The First Affiliated Hospital of Soochow 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>
      After the second-line treatment of patients with non-T790M mutations, chemotherapy with&#xD;
      platinum-containing drugs was used, and chemotherapy-related toxicity was high. Studies have&#xD;
      shown that bevacizumab combined with EGFR TKI have a good trend of benefit. This study is&#xD;
      aimed to evaluate the efficacy and safety of Anlotinib Hydrochloride combined with&#xD;
      first-generation EGFR TKIs as second-line treatment in advanced non-small cell lung cancer .&#xD;
      The patients with IV non-small lung cancer have acquired resistance to prior first-generation&#xD;
      EGFR TKIs and have non-T790M mutation.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">March 30, 2019</start_date>
  <completion_date type="Anticipated">December 20, 2020</completion_date>
  <primary_completion_date type="Anticipated">December 20, 2019</primary_completion_date>
  <phase>N/A</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>
    <intervention_model_description>Anlotinib Hydrochloride Combined With gefitinib or Icotinib</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>PFS（Progress free survival）</measure>
    <time_frame>each 42 days up to PD or death(up to 24 months)</time_frame>
    <description>PFS defined as the time from first dose of study treatment until the first date of either objective disease progression or death due to any cause.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>From randomization until death (up to 24 months)</time_frame>
    <description>OS is defined as the time until death due to any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate (ORR)</measure>
    <time_frame>each 42 days up to intolerance the toxicity or PD (up to 24 months)</time_frame>
    <description>ORR is defined as the percentage of subjects with evidence of a confirmed complete response (CR) or partial response (PR) as per Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1.prior to progression or any further therapy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of Life(QoL)</measure>
    <time_frame>each 42 days up to intolerance the toxicity or PD (up to 24 months)</time_frame>
    <description>use EORTC QLQ-C30(version 3) questionnaire to evaluate the quality of life.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease Control Rate (DCR)</measure>
    <time_frame>each 42 days up to intolerance the toxicity or PD (up to 24 months)</time_frame>
    <description>Defined as the proportion of patients with a documented complete response, partial response, and stable disease (CR + PR + SD) based on RECIST 1.1.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">66</enrollment>
  <condition>Non-Small-Cell Lung</condition>
  <arm_group>
    <arm_group_label>Anlotinib Hydrochloride plus gefitinib or icotinib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Anlotinib Hydrochloride</intervention_name>
    <description>Capsule, P.O. 12mg qd ,days 1-14, 21 days a cycle</description>
    <arm_group_label>Anlotinib Hydrochloride plus gefitinib or icotinib</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Gefitinib</intervention_name>
    <description>Tablet, P.O. 250mg qd</description>
    <arm_group_label>Anlotinib Hydrochloride plus gefitinib or icotinib</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Icotinib</intervention_name>
    <description>Tablet, P.O. 125mg tid</description>
    <arm_group_label>Anlotinib Hydrochloride plus gefitinib or icotinib</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Participants must have histlogically confirmed stage IV non-small cell lung cancer .&#xD;
&#xD;
          -  The initial treatment with gefitinib/icotinib evaluated PR/NC and the efficacy lasted&#xD;
             for more than 6 months, then the disease progressed later. (The efficacy was assessed&#xD;
             as PD according to the evaluation standard of RECIST1.1)&#xD;
&#xD;
          -  At least a measurable lesion that meets the RECIST 1.1 criteria.&#xD;
&#xD;
          -  Any gender. Age ≥18 years and ≤75 years&#xD;
&#xD;
          -  Life expectancy &gt;3 months.&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1.&#xD;
&#xD;
          -  Previously, EGFR gene test showed EGFR exon 19 deletion or exon 21 (L858R) mutation,&#xD;
             and the gene test showed no T790M mutation before enrollment.&#xD;
&#xD;
          -  Adequate organ function: haemoglobin ≥ 90 g/L;neutrophils count ≥1.5×109/L; platelet&#xD;
             count ≥ 90 × 109/L; total bilirubin ≤ 1.5 × ULN ;ALT &lt; 2 × ULN, (ALT &lt; 5 × ULN, for&#xD;
             those with liver metastases);AST &lt; 2 × ULN, (AST &lt; 5 × ULN, for those with liver&#xD;
             metastases); Cr≤1.5× ULN.&#xD;
&#xD;
          -  Echocardiography : LVEF≥50%&#xD;
&#xD;
          -  12-leads electrocardiogram : QTcF&lt;450ms (man), &lt;470ms(woman)&#xD;
&#xD;
          -  Patient informed consent and signed written consent&#xD;
&#xD;
          -  Patient compliance was good and voluntary follow-up, treatment, laboratory testing,&#xD;
             and other research steps were performed as planned.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  The patient has previously received anti-tumor therapy for EGFR TKIs other than&#xD;
             gefitinib and ectinib for lung cancer.&#xD;
&#xD;
          -  Patients that cannot detect EGFR gene, or patients with known T790M mutation.&#xD;
&#xD;
          -  Small cell lung cancer (including lung cancer mixed with small cell lung cancer and&#xD;
             non-small cell lung cancer).&#xD;
&#xD;
          -  CT or MRI shows that the tumor lesion is ≤ 5 mm from the large vessel, or there is a&#xD;
             central tumor that invades the local large blood vessel; or there is a significant&#xD;
             pulmonary cavity or necrotizing tumor.&#xD;
&#xD;
          -  Active brain metastasis, cancerous meningitis, spinal cord compression patients.&#xD;
&#xD;
          -  Other active malignancies that require simultaneous treatment.&#xD;
&#xD;
          -  Has a history of malignant tumors in the past 5 years.&#xD;
&#xD;
          -  Patients with previous anti-tumor treatment-related adverse reactions who have not&#xD;
             recovered to NCI-CTC AE≤1.&#xD;
&#xD;
          -  Abnormal coagulation ,with bleeding tendency or undergoing thrombolysis or&#xD;
             anticoagulant therapy.&#xD;
&#xD;
          -  Renal insufficiency: urinary protein ≥ ++, or confirmed 24-hour urine protein ≥ 1.0g,&#xD;
             or creatinine clearance &lt;60ml / min.&#xD;
&#xD;
          -  Severe acute or chronic infection requiring systemic treatment.&#xD;
&#xD;
          -  Suffering from severe cardiovascular disease: myocardial ischemia ,myocardial or&#xD;
             arrhythmia.&#xD;
&#xD;
          -  Clinically significant hemoptysis occurred within 3 months prior to enrollment; or&#xD;
             significant clinically significant bleeding symptoms or a clear tendency to&#xD;
             hemorrhage.&#xD;
&#xD;
          -  Untreated active hepatitis : Hepatitis B or Hepatitis C&#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>Min Tao, Doctor</last_name>
    <role>Principal Investigator</role>
    <affiliation>The First Affiliated Hospital of Soochow University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Min Tao, Doctor</last_name>
    <phone>008613962125300</phone>
    <email>taomin@suda.edu.cn</email>
  </overall_contact>
  <location>
    <facility>
      <name>The First Affiliated hospital of soochow university</name>
      <address>
        <city>Suzhou</city>
        <state>Jangsu</state>
        <country>China</country>
      </address>
    </facility>
    <contact>
      <last_name>Min Tao, Doctor</last_name>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>December 2018</verification_date>
  <study_first_submitted>December 2, 2018</study_first_submitted>
  <study_first_submitted_qc>December 5, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 6, 2018</study_first_posted>
  <last_update_submitted>January 28, 2019</last_update_submitted>
  <last_update_submitted_qc>January 28, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 30, 2019</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>Gefitinib</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/NCT03766490
org study id: ALTER-L010
nct id: NCT03766490
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
After the second-line treatment of patients with non-T790M mutations, chemotherapy with
      platinum-containing drugs was used, and chemotherapy-related toxicity was high. Studies have
      shown that bevacizumab combined with EGFR TKI have a good trend of benefit. This study is
      aimed to evaluate the efficacy and safety of Anlotinib Hydrochloride combined with
      first-generation EGFR TKIs as second-line treatment in advanced non-small cell lung cancer .
      The patients with IV non-small lung cancer have acquired resistance to prior first-generation
      EGFR TKIs and have non-T790M mutation.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Anlotinib Hydrochloride Combined With gefitinib or Icotinib
primary purpose: Treatment
masking: None (Open Label)
measure: PFS（Progress free survival）
time frame: each 42 days up to PD or death(up to 24 months)
description: PFS defined as the time from first dose of study treatment until the first date of either objective disease progression or death due to any cause.
measure: Overall Survival (OS)
time frame: From randomization until death (up to 24 months)
description: OS is defined as the time until death due to any cause.
measure: Objective Response Rate (ORR)
time frame: each 42 days up to intolerance the toxicity or PD (up to 24 months)
description: ORR is defined as the percentage of subjects with evidence of a confirmed complete response (CR) or partial response (PR) as per Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1.prior to progression or any further therapy.
measure: Quality of Life(QoL)
time frame: each 42 days up to intolerance the toxicity or PD (up to 24 months)
description: use EORTC QLQ-C30(version 3) questionnaire to evaluate the quality of life.
measure: Disease Control Rate (DCR)
time frame: each 42 days up to intolerance the toxicity or PD (up to 24 months)
description: Defined as the proportion of patients with a documented complete response, partial response, and stable disease (CR + PR + SD) based on RECIST 1.1.
arm group label: Anlotinib Hydrochloride plus gefitinib or icotinib
arm group type: Experimental
intervention type: Drug
intervention name: Anlotinib Hydrochloride
description: Capsule, P.O. 12mg qd ,days 1-14, 21 days a cycle
arm group label: Anlotinib Hydrochloride plus gefitinib or icotinib
intervention type: Drug
intervention name: Gefitinib
description: Tablet, P.O. 250mg qd
arm group label: Anlotinib Hydrochloride plus gefitinib or icotinib
intervention type: Drug
intervention name: Icotinib
description: Tablet, P.O. 125mg tid
arm group label: Anlotinib Hydrochloride plus gefitinib or icotinib
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Min Tao, Doctor
role: Principal Investigator
affiliation: The First Affiliated Hospital of Soochow University
last name: Min Tao, Doctor
phone: 008613962125300
email: taomin@suda.edu.cn
facility: 
contact: 
country: China
responsible party type: Sponsor
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Gefitinib