<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/NCT03228277</url>
  </required_header>
  <id_info>
    <org_study_id>KASTT005_BAL_Olita</org_study_id>
    <nct_id>NCT03228277</nct_id>
  </id_info>
  <brief_title>Olmutinib Trial in T790M (+) NSCLC Patients Detected by Liquid Biopsy Using BALF Extracellular Vesicular DNA</brief_title>
  <official_title>Phase II, Multicenter, Single-arm, Open-label Study to Evaluate the Efficacy of Olmutinib(Olita®) in Patients With NSCLC Who Harboring T790M Mutation Confirmed Using DNA Extracted From Extracellular Vesicles in Bronchoalveolar Lavage Fluid</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Konkuk University Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Hanmi Pharmaceutical Company Limited</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Konkuk University Medical Center</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the efficacy of Olmutinib(Olita®) in patients with&#xD;
      T790M-positive non-small cell lung cancer (NSCLC) confirmed using DNA extracted from&#xD;
      extracellular vesicles of bronchoalveolar lavage fluid.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a single-arm, open-label, Phase 2 study to assess the anti-tumor efficacy of&#xD;
      Olmutinib(Olita®) administered to patients with T790M-positive NSCLC confirmed using DNA&#xD;
      extracted from extracellular vesicles in bronchoalveolar lavage fluid as measured by&#xD;
      objective response rate (ORR).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 17, 2017</start_date>
  <completion_date type="Actual">July 31, 2019</completion_date>
  <primary_completion_date type="Actual">July 31, 2018</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>Objective response rate (ORR)</measure>
    <time_frame>Change from baseline at every 6 weeks until disease progression or withdrawal from study, assessed up to 12 months</time_frame>
    <description>defined as the proportion of patients who achieved complete remission(CR) or partial remission(PR) based on RECIST version 1.1</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Disease control rate (DCR)</measure>
    <time_frame>Change from baseline at every 6 weeks until disease progression or withdrawal from study, assessed up to 12 months</time_frame>
    <description>defined as the proportion of patients with a documented CR, PR, and SD during the treatment cycles according to the RECIST version 1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival (PFS)</measure>
    <time_frame>Change from baseline at every 6 weeks until disease progression or withdrawal from study, assessed up to 12 months</time_frame>
    <description>defined as the time from first administration of study drug to determination of tumor progression by RECIST version 1.1 or death due to any cause, whichever occurs first</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">25</enrollment>
  <condition>Non Small Cell Lung Cancer</condition>
  <arm_group>
    <arm_group_label>Olmutinib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single arm of Olmutinib, staring dose of 800 mg</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Olmutinib</intervention_name>
    <description>Patients to be provided with Olmutinib 800mg (2 x 400 mg tablets) once daily (QD)</description>
    <arm_group_label>Olmutinib</arm_group_label>
    <other_name>Olita®</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female, aged at least 19 years&#xD;
&#xD;
          2. Obtained written informed consent&#xD;
&#xD;
          3. Histologically- or cytologically confirmed diagnosis of unresectable Stage IIIB or IV&#xD;
             non-small cell lung cancer.&#xD;
&#xD;
          4. Confirmation that the tumor harbours an EGFR mutation known to be associated with EGFR&#xD;
             TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q).&#xD;
&#xD;
          5. Eastern Cooperative Oncology Group performance status of 0 to 2&#xD;
&#xD;
          6. Prior treatment with at least one line of a single agent EGFR TKI (gefitinib,&#xD;
             erlotinib, afatinib) and confirmed progressive disease after treatment with EGFR TKI&#xD;
&#xD;
               -  Regardless of treatment sequence between previous chemotherapy and EGFR TKI&#xD;
&#xD;
               -  Regardless of whether they were administered conventional chemotherapy, if&#xD;
                  therapy were treated with at least one EGFR TKI&#xD;
&#xD;
          7. Subjects who will undergo bronchoscopy/ BAL procedures and sufficient amount of BAL&#xD;
             fluid is carefully collected for EGFR mutation analysis.&#xD;
&#xD;
          8. Confirmation that the extracellular vesicles (EV) extracted from bronchoalveolar&#xD;
             lavage fluid (BALF) harbour T790M mutation (It can be replaced previous the same&#xD;
             result throughout the follow up period before enrollment.)&#xD;
&#xD;
          9. At least one measurable disease (except brain) at baseline according to RECIST version&#xD;
             1.1&#xD;
&#xD;
         10. Female subjects must be postmenopausal (for at least one year), or, if sexually&#xD;
             active, be practicing an effective method of birth control (e.g., prescription oral&#xD;
             contraceptives, contraceptive injections, intrauterine device, double-barrier method,&#xD;
             contraceptive patch, male partner sterilization) before entry and throughout the&#xD;
             study; and, for those of childbearing potential, have a negative urinary β-hCG&#xD;
             pregnancy test at screening.&#xD;
&#xD;
         11. Male subjects should be willing to use barrier methods which are suitable for sexual&#xD;
             partner throughout the study.&#xD;
&#xD;
         12. Subjects must have signed an informed consent document indicating that they understand&#xD;
             the purpose of and procedures required for the study and are willing to participate in&#xD;
             the study. The subject also must sign and date the consent form before specific&#xD;
             procedures or sampling.&#xD;
&#xD;
         13. Adequate organ function as defined by liver, kidney, and hematologic laboratory&#xD;
             testing as below&#xD;
&#xD;
               -  Absolute neutrophil count (ANC) ≥ 1500/mm3, Platelet ≥ 100,000 /mm3 Hemoglobin&#xD;
                  (Hb) ≥ 9.0g/dL&#xD;
&#xD;
               -  Serum creatinine ≤ upper limit of normal (ULN)&#xD;
&#xD;
               -  AST/ALT/ALP ≤ 3 times ULN, Total bilirubin ≤2.0 mg/dL AST/ALT/ALP ≤ 5 times ULN&#xD;
                  in patients with metastatic lesions to the liver ALP ≤ 5 times ULN in patients&#xD;
                  with metastatic lesions to the bone&#xD;
&#xD;
         14. Expected survival of at least 12 weeks&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Previous treatment with anticancer therapies, EGFR-TKI, olmutinib (HM61713), or other&#xD;
             drugs that target T790M-positive mutant EGFR with sparing of wild-type, Osimertinib&#xD;
             (AZD9291), Rociletinib (CO-1686), investigational agent(s) within 30 days prior to the&#xD;
             first administration of study drug, radiotherapy&#xD;
&#xD;
          2. Treatment with a potent cytochrome P450 (CYP) 3A4 inhibitors or inducers&#xD;
&#xD;
          3. History of any other malignancy EXCEPTIONS are:&#xD;
&#xD;
               -  adequately treated non-melanoma skin cancer, curatively treated in situ cancer of&#xD;
                  the cervix, ductal carcinoma in situ (DCIS) of the breast, thyroid cancer&#xD;
&#xD;
               -  other malignancies diagnosed prior to randomisation and treated with no evidence&#xD;
                  of disease recurrence more than 3 years&#xD;
&#xD;
          4. Any history or presence of clinically relevant cardiovascular abnormalities such as&#xD;
             uncontrolled hypertension, congestive heart failure NYHA classification of III or IV,&#xD;
             unstable angina or poorly controlled arrhythmia as determined by the investigator.&#xD;
             Myocardial infarction within 6 months prior to enrolment. Increased QTc interval &gt; 450&#xD;
             ms on screening ECG&#xD;
&#xD;
          5. Any history of presence of interstitial lung disease&#xD;
&#xD;
          6. Any history or presence of poorly controlled gastrointestinal disorders that could&#xD;
             affect the absorption of the trial drug (e.g. Crohn's disease, ulcerative colitis,&#xD;
             chronic diarrhea, malabsorption).&#xD;
&#xD;
          7. Ongoing active infection with, hepatitis B virus (infection defined as a positive&#xD;
             HbsAg and/ or HBV DNA), hepatitis C virus (infection defined as a positive HCV RNA),&#xD;
             or human immunodeficiency virus (HIV) Type 1/2 infection at the time of screening.&#xD;
&#xD;
          8. Known history of hypersensitivity to active or inactive excipients of study drug&#xD;
             (olmutinib) or drugs with a similar chemical structure of olmutinib&#xD;
&#xD;
          9. Subjects with galactose intolerance, Lapp lactase deficiency or glucose-galactose&#xD;
             malabsorption&#xD;
&#xD;
         10. Symptomatic or uncontrolled central nervous system (CNS) metastases (Patients are&#xD;
             eligible if they have completed their treatment and have recovered from the acute&#xD;
             effects of radiation therapy or surgery prior to the start of study medication, have&#xD;
             discontinued corticosteroid treatment for these metastases for at least 4 weeks and&#xD;
             are neurologically and radiologically stable)&#xD;
&#xD;
         11. Uncontrolled active infectious disease (with the exception of those that are&#xD;
             considered to be needed topical antibiotics, however subjects can be enrolled into the&#xD;
             study after they complete their treatment)&#xD;
&#xD;
         12. Unable to attend all the study visits or comply with study procedures&#xD;
&#xD;
         13. Patients who had received other investigational product within 30 days prior to the&#xD;
             first administration of study drug except for gefitinib, erlotinib, or afatinib&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>19 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Kye Young Lee</last_name>
    <role>Principal Investigator</role>
    <affiliation>Konkuk University Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Konkuk University Medical Center</name>
      <address>
        <city>Seoul</city>
        <zip>05030</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <verification_date>August 2019</verification_date>
  <study_first_submitted>July 17, 2017</study_first_submitted>
  <study_first_submitted_qc>July 20, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 24, 2017</study_first_posted>
  <last_update_submitted>August 25, 2019</last_update_submitted>
  <last_update_submitted_qc>August 25, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">August 28, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Konkuk University Medical Center</investigator_affiliation>
    <investigator_full_name>Kye Young Lee</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Extracellular vesicles</keyword>
  <keyword>Bronchoalveolar lavage fluid</keyword>
  <keyword>Liquid biopsy</keyword>
  <keyword>T790M</keyword>
  <keyword>NSCLC</keyword>
  <keyword>Exosomes</keyword>
  <keyword>EGFR mutation testing</keyword>
  <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>No</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/NCT03228277
org study id: KASTT005_BAL_Olita
nct id: NCT03228277
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
The purpose of this study is to evaluate the efficacy of Olmutinib(Olita®) in patients with
      T790M-positive non-small cell lung cancer (NSCLC) confirmed using DNA extracted from
      extracellular vesicles of bronchoalveolar lavage fluid.
This is a single-arm, open-label, Phase 2 study to assess the anti-tumor efficacy of
      Olmutinib(Olita®) administered to patients with T790M-positive NSCLC confirmed using DNA
      extracted from extracellular vesicles in bronchoalveolar lavage fluid as measured by
      objective response rate (ORR).
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Objective response rate (ORR)
time frame: Change from baseline at every 6 weeks until disease progression or withdrawal from study, assessed up to 12 months
description: defined as the proportion of patients who achieved complete remission(CR) or partial remission(PR) based on RECIST version 1.1
measure: Disease control rate (DCR)
time frame: Change from baseline at every 6 weeks until disease progression or withdrawal from study, assessed up to 12 months
description: defined as the proportion of patients with a documented CR, PR, and SD during the treatment cycles according to the RECIST version 1.1
measure: Progression-free survival (PFS)
time frame: Change from baseline at every 6 weeks until disease progression or withdrawal from study, assessed up to 12 months
description: defined as the time from first administration of study drug to determination of tumor progression by RECIST version 1.1 or death due to any cause, whichever occurs first
arm group label: Olmutinib
arm group type: Experimental
description: Single arm of Olmutinib, staring dose of 800 mg
intervention type: Drug
intervention name: Olmutinib
description: Patients to be provided with Olmutinib 800mg (2 x 400 mg tablets) once daily (QD)
arm group label: Olmutinib
other name: Olita®
criteria: 
gender: All
minimum age: 19 Years
maximum age: N/A
healthy volunteers: No
last name: Kye Young Lee
role: Principal Investigator
affiliation: Konkuk University Medical Center
facility: 
country: Korea, Republic of
responsible party type: Principal Investigator
investigator affiliation: Konkuk University Medical Center
investigator full name: Kye Young Lee
investigator title: Professor
mesh term: Carcinoma, Non-Small-Cell Lung
sharing ipd: No