<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/NCT01718847</url>
  </required_header>
  <id_info>
    <org_study_id>NOV120101-202</org_study_id>
    <nct_id>NCT01718847</nct_id>
  </id_info>
  <brief_title>NOV120101 Phase 2 Study in NSCLC Patients With Aquired Resistance to 1st Generation EGFR Tyrosine Kinase Inhibitors</brief_title>
  <acronym>NSCLC</acronym>
  <official_title>Phase II Exploratory Trial to Evaluate the Efficacy and Safety of NOV120101 (Poziotinib) in Lung Adenocarcinoma Patients With Acquired Resistance to 1st Generation EGFR Tyrosine Kinase Inhibitors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National OncoVenture</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Hanmi Pharmaceutical Company Limited</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>National OncoVenture</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this open-label, single-arm, multi-center phase II trial is to evaluate the&#xD;
      efficacy and safety of novel pan-HER inhibitor, NOV120101 (Poziotinib), as a 2nd line&#xD;
      monotherapy agent in lung adenocarcinoma patients with acquired resistance to prior EGFR&#xD;
      tyrosine kinase inhibitors (TKIs).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Acquired resistance to prior EGFR TKIs is considered as &quot;unmet medical need&quot; in clinical&#xD;
      practice. To evaluate the efficacy of NOV120101 (Poziotinib) as a second-line monotherapeutic&#xD;
      agent, patients with acquired resistance to gefitinib or erlotinib will be enrolled in this&#xD;
      study. Subjects will receive NOV120101 (Poziotinib) 16 mg PO once daily until disease&#xD;
      progression or unacceptable toxicity development. Progression free survival (PFS) will be&#xD;
      analyzed as the primary endpoint in this trial. Secondary endpoints including PFS rate at 16&#xD;
      weeks, ORR and DCR will also be analyzed.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>January 2013</start_date>
  <completion_date type="Actual">September 2014</completion_date>
  <primary_completion_date type="Actual">September 2014</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 (PFS)</measure>
    <time_frame>By 1 year after enrollment of the last subject</time_frame>
    <description>The length of time during and after medication or treatment during which the disease being treated (usually cancer) does not get worse.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>PFS rate at 16 weeks</measure>
    <time_frame>16 weeks</time_frame>
    <description>The proportion of Patients maintaining progress-free status at 16 weeks</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective response rate (ORR)</measure>
    <time_frame>By 1 year after enrollment of the last subject</time_frame>
    <description>The proportion of patients with partial response or complete response at their best tumor treatment evaluation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease control rate (DCR)</measure>
    <time_frame>By 1 year after enrollment of the last subject</time_frame>
    <description>The proportion of patients with CR, PR and/or stable disease (SD)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>By 1 year after enrollment of the last subject</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to progression (TTP)</measure>
    <time_frame>By 1 year after enrollment of the last subject</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to objective response</measure>
    <time_frame>By 1 year after enrollment of the last subject</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of objective response</measure>
    <time_frame>By 1 year after enrollment of the last subject</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of disease control</measure>
    <time_frame>By 1 year after enrollment of the last subject</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of quality of life (QoL) measured by EQ-5D questionnaire</measure>
    <time_frame>baseline and the end of treatment, by 1 year after enrollment of the last subject</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Population pharmacokinetics (PK) of NOV120101 (Poziotinib)</measure>
    <time_frame>By 3 months after enrollment of the last subject</time_frame>
    <description>The study of the sources and correlates of variability in drug concentrations among individuals who are the target patient population receiving clinically relevant doses of a study drug. Certain patient demographic, pathophysiological, and therapeutical features, such as body weight, excretory and metabolic functions, and the presence of other therapies, can regularly alter dose-concentration relationships.</description>
  </other_outcome>
  <other_outcome>
    <measure>Subgroup analyses with the genetic information</measure>
    <time_frame>by 1 year after enrollment of the last patient</time_frame>
    <description>Subgroup analysis, in the context of design and analysis of study drug, refers to looking for pattern in a subset of the subjects according to genotype</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">40</enrollment>
  <condition>Increased Drug Resistance</condition>
  <arm_group>
    <arm_group_label>NOV120101 (Poziotinib)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>16 mg PO once daily until disease progression or unacceptable toxicity development</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>NOV120101 (Poziotinib)</intervention_name>
    <description>16 mg PO once daily until disease progression or unacceptable toxicity development</description>
    <arm_group_label>NOV120101 (Poziotinib)</arm_group_label>
    <other_name>HM781-36B</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female patients aged 20 years or older&#xD;
&#xD;
          2. Pathologically confirmed stage IIIB (unresectable) or IV lung adenocarinoma&#xD;
&#xD;
          3. Patients who have 1 or more than 1 measurable or evaluable but unmeasurable lesions&#xD;
             according to RECIST ver1.1&#xD;
&#xD;
          4. Patients who received prior 1st generation EGFR TKIs (gefitinib or erlotinib)&#xD;
             monotherapy and meet the following criteria:&#xD;
&#xD;
               1. Patients with EGFR mutation (e.g., G719X, exon 19 deletion, L858R, L861Q, etc)&#xD;
                  known to be associated with sensitivity to TKIs&#xD;
&#xD;
               2. Patients who showed objective clinical benefit from treatment with an EGFR TKI as&#xD;
                  defined by either:&#xD;
&#xD;
                    -  Patients who showed complete (CR) or partial response (PR), or&#xD;
&#xD;
                    -  Patients who maintained stable disease (SD) status ≥ 6 months&#xD;
&#xD;
               3. Patients who showed progressive disease (PD, RECIST ver1.1) while on continuous&#xD;
                  treatment with gefitinib or erlotinib within the last 30 days (However, patients&#xD;
                  whose progressive disease is limited in the brain cannot participate in this&#xD;
                  trial.)&#xD;
&#xD;
               4. No intervening systemic chemotherapy between cessation of the EGFR TKI and&#xD;
                  participation of this study&#xD;
&#xD;
          5. Patients who agree to the collection of tumor tissue specimen&#xD;
&#xD;
          6. ECOG performance status ≤ 2&#xD;
&#xD;
          7. Life expectancy of ≥ 12 weeks&#xD;
&#xD;
          8. Adequate hematological, hepatic and renal functions:&#xD;
&#xD;
             WBC ≥ 4,000/mm3, Platelet ≥ 100,000/mm3, Serum creatinine ≤ 1.5 X ULN, AST and ALT ≤&#xD;
             2.5 X ULN, Total bilirubin ≤ 1.5 X ULN&#xD;
&#xD;
          9. Patients who give written informed consent voluntarily&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients who receive IP within 3 days from prior treatment with gefitinib or erlotinib&#xD;
&#xD;
          2. NCI-CTCAE grade &gt; 1 adverse events due to treatment with gefitinib or erlotinib&#xD;
&#xD;
          3. Prior systemic chemo, immuno, hormonal and/or biological therapy except gefitinib or&#xD;
             erlotinib within 4 weeks before IP administration&#xD;
&#xD;
          4. Acquired resistance to EGFR TKI due to conversion of adenocarcinoma into small cell&#xD;
             lung cancer&#xD;
&#xD;
          5. Patients who received major surgery within 4 weeks before IP administration&#xD;
&#xD;
          6. Symptomatic CNS metastases (patients with radiologically and neurologically stable&#xD;
             metastases and being off corticosteroids for at least 4 weeks are able to participate&#xD;
             in this trial.)&#xD;
&#xD;
          7. History of other malignancies except effectively treated non-melanoma skin cancers,&#xD;
             carcinoma in situ of the cervix, ductal carcinoma in situ or effectively treated&#xD;
             malignancy that has been in remission for ≥ 3 years and considered to be cured by&#xD;
             investigator's judgment&#xD;
&#xD;
          8. Known pre-existing interstitial lung disease (ILD)&#xD;
&#xD;
          9. NYHA class III or IV heart failure, uncontrolled hypertension, unstable angina or&#xD;
             myocardial infarction within 6 months, poorly controlled arrhythmia or other&#xD;
             clinically significant cardiovascular abnormalities at investigator's discretion&#xD;
&#xD;
         10. Patients whose left ventricle ejection fraction (LVEF) is below the institutional&#xD;
             lower limit of normal (if no lower limit of normal is defined in the site, the lower&#xD;
             limit is 50%.)&#xD;
&#xD;
         11. Patients with known active hepatitis B, HIV infection, or other uncontrolled&#xD;
             infectious disease&#xD;
&#xD;
         12. Clinically significant or recent acute gastrointestinal disorders with diarrhea as a&#xD;
             major symptom (e.g., Crohn's disease, malabsorption disorders, CTCAE grade ≥ 2&#xD;
             diarrhea due to any etiology)&#xD;
&#xD;
         13. Patients who cannot receive IP by mouth and be diagnosed with clinically significant&#xD;
             gastrointestinal disorders which can prevent administration, transit or absorption of&#xD;
             the IP&#xD;
&#xD;
         14. Pregnancy or breast-feeding&#xD;
&#xD;
         15. Women of childbearing potential (WOCBP) or men who are unwilling to use adequate&#xD;
             contraception or be abstinent during the trial and for at least 2 months after the end&#xD;
             of treatment&#xD;
&#xD;
         16. Patients who received other investigational products except gefitinib and erlotinib&#xD;
             within 4 weeks before participation&#xD;
&#xD;
         17. Patients who cannot participate in this trial by investigator's judgment&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ji-Youn Han, MD. Ph.D</last_name>
    <role>Study Chair</role>
    <affiliation>National Cancer Center, Goyang-si, Gyeonggi-do, Republic of Korea,Asan Medical Center, Songpa-gu, Seoul, Republic of Korea,</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Ki Hyeong Lee, MD, Ph.D</last_name>
    <role>Principal Investigator</role>
    <affiliation>Chungbuk National University Hospital, Cheongju-si, Chungcheongbuk-do, Republic of Korea</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Sang-We Kim, MD, Ph.D</last_name>
    <role>Principal Investigator</role>
    <affiliation>Asan Medical Center, Songpa-gu, Seoul, Republic of Korea</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Young Joo Min, MD, Ph.D</last_name>
    <role>Principal Investigator</role>
    <affiliation>Ulsan University Hospital, Dong-gu, Ulsan, Republic of Korea</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Eunkyung Cho, MD, Ph.D</last_name>
    <role>Principal Investigator</role>
    <affiliation>Gachon University Gil Medical Center, Incheon, Republic of Korea</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Chungbuk National University Hospital</name>
      <address>
        <city>Cheongju-si,</city>
        <state>Chungcheongbuk-do</state>
        <zip>361-711</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Cancer Center</name>
      <address>
        <city>Goyang-si</city>
        <state>Gyeonggi-do</state>
        <zip>410-769</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Asan Medical Center</name>
      <address>
        <city>Songpa-gu</city>
        <state>Seoul</state>
        <zip>138-736</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ulsan University Hospital</name>
      <address>
        <city>Dong-gu</city>
        <state>Ulsan</state>
        <zip>682-714</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gachon University Gil Medical Center</name>
      <address>
        <city>Incheon</city>
        <zip>405-760</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <verification_date>August 2015</verification_date>
  <study_first_submitted>October 22, 2012</study_first_submitted>
  <study_first_submitted_qc>October 28, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 31, 2012</study_first_posted>
  <last_update_submitted>August 13, 2015</last_update_submitted>
  <last_update_submitted_qc>August 13, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 14, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>EGFR Tyrosine Kinase Inhibitor</keyword>
  <keyword>Aquired resistance to EGFR TKI</keyword>
  <keyword>Pan-Her inhibitor</keyword>
  <!-- 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/NCT01718847
org study id: NOV120101-202
nct id: NCT01718847
lead sponsor: 
collaborator: 
has dmc: Yes
The purpose of this open-label, single-arm, multi-center phase II trial is to evaluate the
      efficacy and safety of novel pan-HER inhibitor, NOV120101 (Poziotinib), as a 2nd line
      monotherapy agent in lung adenocarcinoma patients with acquired resistance to prior EGFR
      tyrosine kinase inhibitors (TKIs).
Acquired resistance to prior EGFR TKIs is considered as "unmet medical need" in clinical
      practice. To evaluate the efficacy of NOV120101 (Poziotinib) as a second-line monotherapeutic
      agent, patients with acquired resistance to gefitinib or erlotinib will be enrolled in this
      study. Subjects will receive NOV120101 (Poziotinib) 16 mg PO once daily until disease
      progression or unacceptable toxicity development. Progression free survival (PFS) will be
      analyzed as the primary endpoint in this trial. Secondary endpoints including PFS rate at 16
      weeks, ORR and DCR will also be analyzed.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Progression free survival (PFS)
time frame: By 1 year after enrollment of the last subject
description: The length of time during and after medication or treatment during which the disease being treated (usually cancer) does not get worse.
measure: PFS rate at 16 weeks
time frame: 16 weeks
description: The proportion of Patients maintaining progress-free status at 16 weeks
measure: Objective response rate (ORR)
time frame: By 1 year after enrollment of the last subject
description: The proportion of patients with partial response or complete response at their best tumor treatment evaluation
measure: Disease control rate (DCR)
time frame: By 1 year after enrollment of the last subject
description: The proportion of patients with CR, PR and/or stable disease (SD)
measure: Overall survival (OS)
time frame: By 1 year after enrollment of the last subject
measure: Time to progression (TTP)
time frame: By 1 year after enrollment of the last subject
measure: Time to objective response
time frame: By 1 year after enrollment of the last subject
measure: Duration of objective response
time frame: By 1 year after enrollment of the last subject
measure: Duration of disease control
time frame: By 1 year after enrollment of the last subject
measure: Change of quality of life (QoL) measured by EQ-5D questionnaire
time frame: baseline and the end of treatment, by 1 year after enrollment of the last subject
measure: Population pharmacokinetics (PK) of NOV120101 (Poziotinib)
time frame: By 3 months after enrollment of the last subject
description: The study of the sources and correlates of variability in drug concentrations among individuals who are the target patient population receiving clinically relevant doses of a study drug. Certain patient demographic, pathophysiological, and therapeutical features, such as body weight, excretory and metabolic functions, and the presence of other therapies, can regularly alter dose-concentration relationships.
measure: Subgroup analyses with the genetic information
time frame: by 1 year after enrollment of the last patient
description: Subgroup analysis, in the context of design and analysis of study drug, refers to looking for pattern in a subset of the subjects according to genotype
arm group label: NOV120101 (Poziotinib)
arm group type: Experimental
description: 16 mg PO once daily until disease progression or unacceptable toxicity development
intervention type: Drug
intervention name: NOV120101 (Poziotinib)
description: 16 mg PO once daily until disease progression or unacceptable toxicity development
arm group label: NOV120101 (Poziotinib)
other name: HM781-36B
criteria: 
gender: All
minimum age: 20 Years
maximum age: N/A
healthy volunteers: No
last name: Ji-Youn Han, MD. Ph.D
role: Study Chair
affiliation: National Cancer Center, Goyang-si, Gyeonggi-do, Republic of Korea,Asan Medical Center, Songpa-gu, Seoul, Republic of Korea,
last name: Ki Hyeong Lee, MD, Ph.D
role: Principal Investigator
affiliation: Chungbuk National University Hospital, Cheongju-si, Chungcheongbuk-do, Republic of Korea
last name: Sang-We Kim, MD, Ph.D
role: Principal Investigator
affiliation: Asan Medical Center, Songpa-gu, Seoul, Republic of Korea
last name: Young Joo Min, MD, Ph.D
role: Principal Investigator
affiliation: Ulsan University Hospital, Dong-gu, Ulsan, Republic of Korea
last name: Eunkyung Cho, MD, Ph.D
role: Principal Investigator
affiliation: Gachon University Gil Medical Center, Incheon, Republic of Korea
facility: 
facility: 
facility: 
facility: 
facility: 
country: Korea, Republic of
responsible party type: Sponsor