<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/NCT04499794</url>
  </required_header>
  <id_info>
    <org_study_id>NCC2064</org_study_id>
    <nct_id>NCT04499794</nct_id>
  </id_info>
  <brief_title>The Study of Exosome EML4-ALK Fusion in NSCLC Clinical Diagnosis and Dynamic Monitoring</brief_title>
  <official_title>The Study of Exosome EML4-ALK Fusion in NSCLC Clinical Diagnosis and Dynamic Monitoring</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Cancer Institute and Hospital, Chinese Academy of Medical Sciences</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Cancer Institute and Hospital, Chinese Academy of Medical Sciences</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>
      The application of ALK inhibitors in the first-line cancer treatment can significantly&#xD;
      increase the PFS and ORR of patients those with EML4-ALK fusion. The contemporary clinical&#xD;
      ALK fusion detection are mainly via FISH and ICH while biopsies are needed. For locations&#xD;
      where are difficult to take biopsies, these routine examinations can hardly been adopted.&#xD;
      Apart from these, part of ALK fusion patients are resistant to ALK inhibitors, also making an&#xD;
      accurate and efficient prognostic indicator for efficacy evaluation and identifying high-risk&#xD;
      recurrent population an urgent priority.&#xD;
&#xD;
      The bilayer membrane structure of exosome helps maintain its internal genetic stability,&#xD;
      making detection of EML4-ALK fusion via plasma exosomes in advanced NSCLC patients a feasible&#xD;
      way, which might provide a non-invasive and more convenient approach for NSCLC diagnosis and&#xD;
      efficacy monitoring. Firstly, this study will evaluate the performance of exosome EML4-ALK&#xD;
      fusion detection in NSCLC diagnosis, which sensitivity and specificity would be compared with&#xD;
      the FDA approved IHC (ALK [D5F3] CDx Assay) test. Subsequently, this study would monitor the&#xD;
      dynamic changes of EML4-ALK fusion in exosome examination diagnosed ALK fusion positive NSCLC&#xD;
      patients both before and after treatment. It aims to prospectively evaluate the potential&#xD;
      value of this approach on efficacy and prognosis prediction in NSCLC therapy and determining&#xD;
      whether exosome ALK fusion could assess the curative effect more accurately than imaging&#xD;
      examination and tumor markers. Thirdly, FISH diagnosed EML4-ALK positive NSCLC patients will&#xD;
      be divided into the positive or negative subgroup according to their post-treatment exosome&#xD;
      ALK fusion expression which were determined at 2-3 months after ALK inhibitor were adopted.&#xD;
      The prognostic value of monitoring exosome EML4-ALK fusion expression is assessed through the&#xD;
      comparison of patients PFS and OS.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Anticipated">August 1, 2020</start_date>
  <completion_date type="Anticipated">March 31, 2025</completion_date>
  <primary_completion_date type="Anticipated">July 31, 2024</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>ORR</measure>
    <time_frame>6-8 weeks</time_frame>
    <description>the ORR of those NSCLC patients receive ALK inhibitors treatment according to exosome ALK fusion diagnosis and FISH examination</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>PFS</measure>
    <time_frame>36 months</time_frame>
    <description>the PFS of those NSCLC patients receive ALK inhibitors treatment according to exosome ALK fusion diagnosis and FISH examination</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">75</enrollment>
  <condition>Untreated Advanced NSCLC Patients</condition>
  <condition>FISH Identified ALK Fusion Positive or Negative</condition>
  <arm_group>
    <arm_group_label>FISH diagnosed EML4-ALK fusion positive NSCLC group</arm_group_label>
  </arm_group>
  <arm_group>
    <arm_group_label>FISH diagnosed EML4-ALK fusion negative NSCLC group</arm_group_label>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ALK inhibitor</intervention_name>
    <description>ALK inhibitor treatment on ALK fusion positive NSCLC patients</description>
    <arm_group_label>FISH diagnosed EML4-ALK fusion positive NSCLC group</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        advanced NSCLC patients&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  All eligible patients must have histologically or cytologically confirmed stage&#xD;
             IIIB-IV unresectable NSCLC positive or negative for EML4-ALK4 fusion as defined by&#xD;
             FISH. Patients must have an ECOG PS of 0- 1 and have at least 1 measurable lesions&#xD;
             (RECIST 1.1 standard). For eligible patients, prior ALK inhibitor therapy or previous&#xD;
             systemic anticancer therapy is not allowed or has been completed over 12 months.&#xD;
             Patients with brain metastasis are eligible only in a stable central nervous system&#xD;
             condition and treatment outcome, cannot receive glucocorticoids and drugs prohibited&#xD;
             in the exclusion criteria ≤14 days before the first dose of study drug.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Eligible patients must not have received any major surgery ≤28 days before the first&#xD;
             dose of study drug and must not have received any minor surgery or radiotherapy ≤14&#xD;
             days before the first dose of study drug. Any acute toxic reaction must have recovered&#xD;
             to ≤ Grade 1 (except for hair loss). Patients with carcinomatous meningitis,&#xD;
             leptomeningeal disease or spinal cord compression must be excluded.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Yutao LIU, Doctor</last_name>
    <role>Principal Investigator</role>
    <affiliation>Cancer Institute and Hospital, Chinese Academy of Medical Sciences</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Yutao LIU, Doctor</last_name>
    <phone>+86 13911901165</phone>
    <email>13911901165@139.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Cancer Hospital Chinese Academy of Medical Sciences</name>
      <address>
        <city>Beijing</city>
        <zip>100021</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Yutao LIU, Doctor</last_name>
      <phone>13911901165</phone>
      <email>13911901165@139.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <reference>
    <citation>Hyun KA, Kim J, Gwak H, Jung HI. Isolation and enrichment of circulating biomarkers for cancer screening, detection, and diagnostics. Analyst. 2016 Jan 21;141(2):382-92. doi: 10.1039/c5an01762a.</citation>
    <PMID>26588824</PMID>
  </reference>
  <reference>
    <citation>Cazzoli R, Buttitta F, Di Nicola M, Malatesta S, Marchetti A, Rom WN, Pass HI. microRNAs derived from circulating exosomes as noninvasive biomarkers for screening and diagnosing lung cancer. J Thorac Oncol. 2013 Sep;8(9):1156-62. doi: 10.1097/JTO.0b013e318299ac32.</citation>
    <PMID>23945385</PMID>
  </reference>
  <reference>
    <citation>Castellanos-Rizaldos E, Zhang X, Tadigotla VR, Grimm DG, Karlovich C, Raez LE, Skog JK. Exosome-based detection of activating and resistance EGFR mutations from plasma of non-small cell lung cancer patients. Oncotarget. 2019 Apr 23;10(30):2911-2920. doi: 10.18632/oncotarget.26885. eCollection 2019 Apr 23.</citation>
    <PMID>31080561</PMID>
  </reference>
  <reference>
    <citation>Tong Y, Zhao Z, Liu B, Bao A, Zheng H, Gu J, McGrath M, Xia Y, Tan B, Song C, Li Y. 5'/ 3' imbalance strategy to detect ALK fusion genes in circulating tumor RNA from patients with non-small cell lung cancer. J Exp Clin Cancer Res. 2018 Mar 27;37(1):68. doi: 10.1186/s13046-018-0735-1.</citation>
    <PMID>29587818</PMID>
  </reference>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>July 31, 2020</study_first_submitted>
  <study_first_submitted_qc>July 31, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 5, 2020</study_first_posted>
  <last_update_submitted>July 31, 2020</last_update_submitted>
  <last_update_submitted_qc>July 31, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">August 5, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Cancer Institute and Hospital, Chinese Academy of Medical Sciences</investigator_affiliation>
    <investigator_full_name>Yutao Liu</investigator_full_name>
    <investigator_title>Physician</investigator_title>
  </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>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </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/NCT04499794
org study id: NCC2064
nct id: NCT04499794
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
The application of ALK inhibitors in the first-line cancer treatment can significantly
      increase the PFS and ORR of patients those with EML4-ALK fusion. The contemporary clinical
      ALK fusion detection are mainly via FISH and ICH while biopsies are needed. For locations
      where are difficult to take biopsies, these routine examinations can hardly been adopted.
      Apart from these, part of ALK fusion patients are resistant to ALK inhibitors, also making an
      accurate and efficient prognostic indicator for efficacy evaluation and identifying high-risk
      recurrent population an urgent priority.

      The bilayer membrane structure of exosome helps maintain its internal genetic stability,
      making detection of EML4-ALK fusion via plasma exosomes in advanced NSCLC patients a feasible
      way, which might provide a non-invasive and more convenient approach for NSCLC diagnosis and
      efficacy monitoring. Firstly, this study will evaluate the performance of exosome EML4-ALK
      fusion detection in NSCLC diagnosis, which sensitivity and specificity would be compared with
      the FDA approved IHC (ALK [D5F3] CDx Assay) test. Subsequently, this study would monitor the
      dynamic changes of EML4-ALK fusion in exosome examination diagnosed ALK fusion positive NSCLC
      patients both before and after treatment. It aims to prospectively evaluate the potential
      value of this approach on efficacy and prognosis prediction in NSCLC therapy and determining
      whether exosome ALK fusion could assess the curative effect more accurately than imaging
      examination and tumor markers. Thirdly, FISH diagnosed EML4-ALK positive NSCLC patients will
      be divided into the positive or negative subgroup according to their post-treatment exosome
      ALK fusion expression which were determined at 2-3 months after ALK inhibitor were adopted.
      The prognostic value of monitoring exosome EML4-ALK fusion expression is assessed through the
      comparison of patients PFS and OS.
observational model: Cohort
time perspective: Prospective
measure: ORR
time frame: 6-8 weeks
description: the ORR of those NSCLC patients receive ALK inhibitors treatment according to exosome ALK fusion diagnosis and FISH examination
measure: PFS
time frame: 36 months
description: the PFS of those NSCLC patients receive ALK inhibitors treatment according to exosome ALK fusion diagnosis and FISH examination
arm group label: FISH diagnosed EML4-ALK fusion positive NSCLC group
arm group label: FISH diagnosed EML4-ALK fusion negative NSCLC group
intervention type: Drug
intervention name: ALK inhibitor
description: ALK inhibitor treatment on ALK fusion positive NSCLC patients
arm group label: FISH diagnosed EML4-ALK fusion positive NSCLC group
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Yutao LIU, Doctor
role: Principal Investigator
affiliation: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
last name: Yutao LIU, Doctor
phone: +86 13911901165
email: 13911901165@139.com
facility: 
status: Recruiting
contact: 
country: China
citation: Hyun KA, Kim J, Gwak H, Jung HI. Isolation and enrichment of circulating biomarkers for cancer screening, detection, and diagnostics. Analyst. 2016 Jan 21;141(2):382-92. doi: 10.1039/c5an01762a.
PMID: 26588824
citation: Cazzoli R, Buttitta F, Di Nicola M, Malatesta S, Marchetti A, Rom WN, Pass HI. microRNAs derived from circulating exosomes as noninvasive biomarkers for screening and diagnosing lung cancer. J Thorac Oncol. 2013 Sep;8(9):1156-62. doi: 10.1097/JTO.0b013e318299ac32.
PMID: 23945385
citation: Castellanos-Rizaldos E, Zhang X, Tadigotla VR, Grimm DG, Karlovich C, Raez LE, Skog JK. Exosome-based detection of activating and resistance EGFR mutations from plasma of non-small cell lung cancer patients. Oncotarget. 2019 Apr 23;10(30):2911-2920. doi: 10.18632/oncotarget.26885. eCollection 2019 Apr 23.
PMID: 31080561
citation: Tong Y, Zhao Z, Liu B, Bao A, Zheng H, Gu J, McGrath M, Xia Y, Tan B, Song C, Li Y. 5'/ 3' imbalance strategy to detect ALK fusion genes in circulating tumor RNA from patients with non-small cell lung cancer. J Exp Clin Cancer Res. 2018 Mar 27;37(1):68. doi: 10.1186/s13046-018-0735-1.
PMID: 29587818
responsible party type: Principal Investigator
investigator affiliation: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
investigator full name: Yutao Liu
investigator title: Physician
mesh term: Carcinoma, Non-Small-Cell Lung
sharing ipd: Undecided