<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/NCT03257735</url>
  </required_header>
  <id_info>
    <org_study_id>A2017-003</org_study_id>
    <nct_id>NCT03257735</nct_id>
  </id_info>
  <brief_title>A Study of the Gene Mutation Status in Cerebrospinal Fluid, Blood and Tumor Tissue of Non-small Cell Lung Cancer Patients With Brain Metastases</brief_title>
  <official_title>A Prospective and Observational Study of the Consistency of Gene Mutation Status Between Cerebrospinal Fluid, Blood and Tumor Tissue,and Correlation With Efficacy in Non-small Cell Lung Cancer Patients With Brain Metastases</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sun Yat-sen University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sun Yat-sen University</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>
      Primary lung cancer is one of the most common malignancies in China, with 57 percent of&#xD;
      patients being diagnosed at advanced stage. At present, advanced lung cancer has entered the&#xD;
      era of precise treatment. So it is very important to determine the gene mutation status of&#xD;
      the tumor and prescribe drugs at the targets. Liquid biopsy is a suitable alternative when&#xD;
      tumor tissues are difficult to obtain. Liquid biopsy technique refers to the use of human&#xD;
      body fluid as a sample source to detect the information of related diseases, including blood,&#xD;
      urine, saliva and cerebrospinal fluid. It is non-invasive, fast and simple, and can avoid the&#xD;
      problem of insufficient sample size and support for repeated sampling to continuously monitor&#xD;
      disease.&#xD;
&#xD;
      With the increasing incidence of lung cancer and the development of diagnosis and treatment&#xD;
      technology, the survival period of patients has been extended, and the incidence and&#xD;
      diagnosis rate of the brain metastasis of lung cancer have increased year by year. The brain&#xD;
      metastasis of lung cancer is the most common type of brain metastatic tumor. The incidence&#xD;
      rate is about 40-50%, and the prognosis is poor--the natural median survival period is about&#xD;
      1-2 months. Because of the impractical intracranial tumor biopsy and very low level of DNA in&#xD;
      peripheral blood, cerebrospinal fluid, which makes close contact with brain tumors, becomes&#xD;
      potential available samples. Several studies have shown that genetic testing of cerebrospinal&#xD;
      fluid is feasible. Therefore, this study aims to test the cerebrospinal fluid, blood and&#xD;
      tissue by the latest second-generation sequencing technology at different time points, to&#xD;
      dynamically monitor the gene mutation status of cerebrospinal fluid, blood and tissue, to&#xD;
      explore the role of cerebrospinal fluid biopsy in the diagnosis and treatment of non-small&#xD;
      cell lung cancer with brain metastases.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">May 1, 2017</start_date>
  <completion_date type="Anticipated">May 31, 2019</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2018</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Change from baseline gene mutation status at 2 months</measure>
    <time_frame>2 months</time_frame>
    <description>compare the gene mutation status of cerebrospinal fluid,blood and tumor tissue at baseline and after the first session</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from second line gene mutation status at 6 months</measure>
    <time_frame>6 months</time_frame>
    <description>compare the gene mutation status of cerebrospinal fluid,blood and tumor tissue after the first session and at the time of tumor progression</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>PFS</measure>
    <time_frame>From date of randomization until the date of first documented progression or date of death from any cause,whichever came first,assessed up to 60 months.</time_frame>
    <description>progression-free survival</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>OS</measure>
    <time_frame>From date of randomization until the date of death from any cause,assessed up to 60 months</time_frame>
    <description>overall survival</description>
  </secondary_outcome>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Lung Cancer</condition>
  <condition>Brain Metastases</condition>
  <condition>Cerebrospinal Fluid</condition>
  <condition>Next-generation Sequencing</condition>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>next-generation sequencing</intervention_name>
    <description>Patients' cerebrospinal fluid, blood and tumor tissue were collected within 3 days before treatment at diagnosis.&#xD;
Patients' cerebrospinal fluid and blood were extracted at the time of first evaluation of efficacy after treatment (TKI began after 1 month or chemotherapy after 2 cycles).&#xD;
Patients' cerebrospinal fluid and blood were extracted at first time of tumor progression，and re-biopsy of tumor tissue was done as much as possible.&#xD;
All the samples were tested by next-generation sequencing.</description>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      We plan to detect the patients' cerebrospinal fluid,blood and tumor tissue with the method of&#xD;
      next-generation sequencing.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patients were histologically confirmed with NSCLC and identified with new brain metastases&#xD;
        by MRI.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female, aged over 18 and less than 75 years old&#xD;
&#xD;
          2. The estimated survival period is greater than 12 weeks&#xD;
&#xD;
          3. ECOG score is less than 2&#xD;
&#xD;
          4. Histological diagnosis is non-small cell lung cancer, and there are enough tissue&#xD;
             specimens for lung cancer related gene detection&#xD;
&#xD;
          5. The brain metastasis is confirmed by brain MRI, and the first line treatment of brain&#xD;
             metastasis was considered as chemotherapy or target therapy&#xD;
&#xD;
          6. There must be at least one evaluable lesion based on the criteria of RECIST 1.1&#xD;
             (maximum diameter at least 10mm on spiral CT and MRI)&#xD;
&#xD;
          7. Patients are tolerable for lumbar puncture with no contraindication&#xD;
&#xD;
          8. Patients are able to comply with the research requirements and follow-up procedures&#xD;
&#xD;
          9. Patients must sign the informed consent prior to the beginning of any substantive test&#xD;
             procedure (informed consent is subject to approval of the independent ethics&#xD;
             committee)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Brain metastases were treated&#xD;
&#xD;
          2. Intracranial symptoms were obvious, and radiotherapy/surgery was considered in the&#xD;
             first line treatment&#xD;
&#xD;
          3. Histological specimens are not enough to detect lung cancer related genes&#xD;
&#xD;
          4. Patients were suffering from other types of malignancy&#xD;
&#xD;
          5. Patients have any contraindications of lumbar puncture&#xD;
&#xD;
          6. Patients have any uncontrolled systemic disease, including active infection,&#xD;
             uncontrolled high blood pressure, diabetes, unstable angina and congestive heart&#xD;
             failure, myocardial infarction (1 year) before the start of treatment, severe&#xD;
             arrhythmia that needs drugs therapy, coagulant function abnormality, liver or kidney&#xD;
             or metabolic disease&#xD;
&#xD;
          7. Pregnant and lactating pregnant women&#xD;
&#xD;
          8. Patients were not willing to be followed up&#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>Likun Chen, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Sun Yat-sen University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Delan Li, master</last_name>
    <phone>18676188892</phone>
    <email>lidl@sysucc.org.cn</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Likun Chen, PhD</last_name>
    <phone>13798019964</phone>
    <email>chenlk@sysucc.org.cn</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Sun Yat-sen University Cancer Center</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <zip>510000</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Delan Li, master</last_name>
      <phone>18676188892</phone>
      <email>lidl@sysucc.org.cn</email>
    </contact>
    <contact_backup>
      <last_name>Likun Chen, PhD</last_name>
      <phone>13798019964</phone>
      <email>chenlk@sysucc.org.cn</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>August 5, 2017</study_first_submitted>
  <study_first_submitted_qc>August 21, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 22, 2017</study_first_posted>
  <last_update_submitted>August 21, 2017</last_update_submitted>
  <last_update_submitted_qc>August 21, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 22, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Sun Yat-sen University</investigator_affiliation>
    <investigator_full_name>Li-kun Chen</investigator_full_name>
    <investigator_title>Chief Physician</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Neoplasms</mesh_term>
    <mesh_term>Neoplasm Metastasis</mesh_term>
    <mesh_term>Brain Neoplasms</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Individual participant data are not available to others.</ipd_description>
  </patient_data>
  <!-- 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/NCT03257735
org study id: A2017-003
nct id: NCT03257735
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Primary lung cancer is one of the most common malignancies in China, with 57 percent of
      patients being diagnosed at advanced stage. At present, advanced lung cancer has entered the
      era of precise treatment. So it is very important to determine the gene mutation status of
      the tumor and prescribe drugs at the targets. Liquid biopsy is a suitable alternative when
      tumor tissues are difficult to obtain. Liquid biopsy technique refers to the use of human
      body fluid as a sample source to detect the information of related diseases, including blood,
      urine, saliva and cerebrospinal fluid. It is non-invasive, fast and simple, and can avoid the
      problem of insufficient sample size and support for repeated sampling to continuously monitor
      disease.

      With the increasing incidence of lung cancer and the development of diagnosis and treatment
      technology, the survival period of patients has been extended, and the incidence and
      diagnosis rate of the brain metastasis of lung cancer have increased year by year. The brain
      metastasis of lung cancer is the most common type of brain metastatic tumor. The incidence
      rate is about 40-50%, and the prognosis is poor--the natural median survival period is about
      1-2 months. Because of the impractical intracranial tumor biopsy and very low level of DNA in
      peripheral blood, cerebrospinal fluid, which makes close contact with brain tumors, becomes
      potential available samples. Several studies have shown that genetic testing of cerebrospinal
      fluid is feasible. Therefore, this study aims to test the cerebrospinal fluid, blood and
      tissue by the latest second-generation sequencing technology at different time points, to
      dynamically monitor the gene mutation status of cerebrospinal fluid, blood and tissue, to
      explore the role of cerebrospinal fluid biopsy in the diagnosis and treatment of non-small
      cell lung cancer with brain metastases.
observational model: Case-Only
time perspective: Prospective
measure: Change from baseline gene mutation status at 2 months
time frame: 2 months
description: compare the gene mutation status of cerebrospinal fluid,blood and tumor tissue at baseline and after the first session
measure: Change from second line gene mutation status at 6 months
time frame: 6 months
description: compare the gene mutation status of cerebrospinal fluid,blood and tumor tissue after the first session and at the time of tumor progression
measure: PFS
time frame: From date of randomization until the date of first documented progression or date of death from any cause,whichever came first,assessed up to 60 months.
description: progression-free survival
measure: OS
time frame: From date of randomization until the date of death from any cause,assessed up to 60 months
description: overall survival
intervention type: Diagnostic Test
intervention name: next-generation sequencing
description: Patients' cerebrospinal fluid, blood and tumor tissue were collected within 3 days before treatment at diagnosis.
Patients' cerebrospinal fluid and blood were extracted at the time of first evaluation of efficacy after treatment (TKI began after 1 month or chemotherapy after 2 cycles).
Patients' cerebrospinal fluid and blood were extracted at first time of tumor progression，and re-biopsy of tumor tissue was done as much as possible.
All the samples were tested by next-generation sequencing.
We plan to detect the patients' cerebrospinal fluid,blood and tumor tissue with the method of
      next-generation sequencing.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Likun Chen, PhD
role: Principal Investigator
affiliation: Sun Yat-sen University
last name: Delan Li, master
phone: 18676188892
email: lidl@sysucc.org.cn
last name: Likun Chen, PhD
phone: 13798019964
email: chenlk@sysucc.org.cn
facility: 
status: Recruiting
contact: 
contact backup: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Sun Yat-sen University
investigator full name: Li-kun Chen
investigator title: Chief Physician
mesh term: Lung Neoplasms
mesh term: Neoplasm Metastasis
mesh term: Brain Neoplasms
sharing ipd: No
ipd description: Individual participant data are not available to others.