<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/NCT01688713</url>
  </required_header>
  <id_info>
    <org_study_id>ZhejiangCH-LCBM-1202</org_study_id>
    <nct_id>NCT01688713</nct_id>
  </id_info>
  <brief_title>Phase II Trial of Double Dose of Icotinib in Treating Brain Metastases From Non-small Cell Lung Cancer</brief_title>
  <sponsors>
    <lead_sponsor>
      <agency>Zhejiang Cancer Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Zhejiang Cancer Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Brain metastases, a common complication,occur in 25-40% of patients with non-small cell lung&#xD;
      cancer (NSCLC). Whole-brain radiation therapy(WBRT) and Stereotactic Radiosurgery (SRS) are&#xD;
      important approaches to the treatment of brain metastases from NSCLC. Known to us, epidermal&#xD;
      growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) can pass through the&#xD;
      blood-brain barrier and show promising antitumor activity against brain metastases from&#xD;
      NSCLC, especially for EGFR mutation patients. However, due to the lower concentration of&#xD;
      tyrosine kinase inhibitors (TKIs) in the cerebrospinal fluid and its inevitable emergence of&#xD;
      drug resistance, brain metastases will be refractory or resistant to standard-dose EGFR&#xD;
      inhibitors. Icotinib is one agent of EGFR-TKIs. The previous studies have shown that the&#xD;
      Icotinib conventional dose (125mg, TID) is far from reached its maximum tolerable dose. It is&#xD;
      a challenge whether the further dose escalation of Icotinib will enhance its concentration in&#xD;
      cerebrospinal fluid and thereby improve its therapeutic effect. Here the investigators&#xD;
      examine the therapeutic effect and side-effect of double dose of Icitinib in treating&#xD;
      patients with brain metastases from NSCLC who have suffered from the failure of conventional&#xD;
      dose treatment.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>August 2012</start_date>
  <completion_date type="Anticipated">September 2015</completion_date>
  <primary_completion_date type="Anticipated">February 2015</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 (intracranial lesions)</measure>
    <time_frame>2 years</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Partial response rate of intracranial lesions</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Partial response rate of extracranial lesion</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health-related quality of life quality</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>number of adverse events such as skin rash,diarrhea ,abnormal liver function and so on</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Brain Metastases</condition>
  <condition>Non-small Cell Lung Cancer</condition>
  <arm_group>
    <arm_group_label>Icotinib,Brain metastases</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Icotinib</intervention_name>
    <description>The patients will receive Icotinib in doses of 250mg thrice per day until disease progression or undue toxicity.</description>
    <arm_group_label>Icotinib,Brain metastases</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histological or cytologic diagnosis of NSCLC&#xD;
&#xD;
          -  Patients with disease progression after local treatment(WBRT and/or SRS) combined with&#xD;
             Icotinib treatment.&#xD;
&#xD;
          -  Patients with EGFR mutation or the lesions that remains stable for more than 3 months&#xD;
             after local treatment(WBRT and/or SRS) combined with Icotinib treatment.&#xD;
&#xD;
          -  ECOG performance status 0-2&#xD;
&#xD;
          -  Doctors consider the patients will not benefit from local treatment(WBRT and/or SRS)&#xD;
&#xD;
          -  Expected survival of greater than 3 months&#xD;
&#xD;
          -  Age: 18-75 years&#xD;
&#xD;
          -  The patients with key organs maintenance of basic function: Hemoglobin ≥ 9g/dL, White&#xD;
             Blood Cell ≥ 3×109/L, Neutrophil count ≥ 1.5×109/L, platelets ≥ 80×109/L, total&#xD;
             bilirubin &lt; 1.5 times of the upper normal values, Alanine transaminase (ALT) and&#xD;
             aspartate transaminase (AST) &lt; 2.5 of the upper normal values, the serum creatinine &lt;&#xD;
             1.5 times of the upper normal values&#xD;
&#xD;
          -  Signed informed consent document on file.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Brain metastasis without local treatment before&#xD;
&#xD;
          -  Patients without the treatment of Icotinib before or the therapeutic time less than 3&#xD;
             months&#xD;
&#xD;
          -  More than 3 extracranial organs have metastatic lesions&#xD;
&#xD;
          -  The patient with other type malignant tumors before&#xD;
&#xD;
          -  The patient with fertility capacity, but without contraceptive application&#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>Weimin Mao, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Zhejiang Cancer Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Yun Fan, MD</last_name>
    <phone>0086-571-88122192</phone>
    <email>fanyun@csco.org.cn</email>
  </overall_contact>
  <location>
    <facility>
      <name>Zhejiang Cancer Hospital</name>
      <address>
        <city>Hangzhou</city>
        <state>Zhejiang</state>
        <zip>310022</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Yun Fan, MD</last_name>
      <phone>0086-571-88122192</phone>
      <email>fanyun@csco.org.cn</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>September 2012</verification_date>
  <study_first_submitted>August 27, 2012</study_first_submitted>
  <study_first_submitted_qc>September 19, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 20, 2012</study_first_posted>
  <last_update_submitted>September 19, 2012</last_update_submitted>
  <last_update_submitted_qc>September 19, 2012</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 20, 2012</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>Lung Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Non-Small-Cell Lung</mesh_term>
    <mesh_term>Neoplasm Metastasis</mesh_term>
    <mesh_term>Brain Neoplasms</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/NCT01688713
org study id: ZhejiangCH-LCBM-1202
nct id: NCT01688713
lead sponsor: 
has dmc: Yes
Brain metastases, a common complication,occur in 25-40% of patients with non-small cell lung
      cancer (NSCLC). Whole-brain radiation therapy(WBRT) and Stereotactic Radiosurgery (SRS) are
      important approaches to the treatment of brain metastases from NSCLC. Known to us, epidermal
      growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) can pass through the
      blood-brain barrier and show promising antitumor activity against brain metastases from
      NSCLC, especially for EGFR mutation patients. However, due to the lower concentration of
      tyrosine kinase inhibitors (TKIs) in the cerebrospinal fluid and its inevitable emergence of
      drug resistance, brain metastases will be refractory or resistant to standard-dose EGFR
      inhibitors. Icotinib is one agent of EGFR-TKIs. The previous studies have shown that the
      Icotinib conventional dose (125mg, TID) is far from reached its maximum tolerable dose. It is
      a challenge whether the further dose escalation of Icotinib will enhance its concentration in
      cerebrospinal fluid and thereby improve its therapeutic effect. Here the investigators
      examine the therapeutic effect and side-effect of double dose of Icitinib in treating
      patients with brain metastases from NSCLC who have suffered from the failure of conventional
      dose treatment.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Progression-free survival (intracranial lesions)
time frame: 2 years
measure: Partial response rate of intracranial lesions
time frame: 2 years
measure: Partial response rate of extracranial lesion
time frame: 2 years
measure: Overall survival
time frame: 3 years
measure: Health-related quality of life quality
time frame: 2 years
measure: number of adverse events such as skin rash,diarrhea ,abnormal liver function and so on
time frame: 2 years
arm group label: Icotinib,Brain metastases
arm group type: Experimental
intervention type: Drug
intervention name: Icotinib
description: The patients will receive Icotinib in doses of 250mg thrice per day until disease progression or undue toxicity.
arm group label: Icotinib,Brain metastases
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Weimin Mao, MD
role: Principal Investigator
affiliation: Zhejiang Cancer Hospital
last name: Yun Fan, MD
phone: 0086-571-88122192
email: fanyun@csco.org.cn
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Sponsor
mesh term: Lung Neoplasms
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Neoplasm Metastasis
mesh term: Brain Neoplasms