<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/NCT03770988</url>
  </required_header>
  <id_info>
    <org_study_id>4-2017-1193</org_study_id>
    <nct_id>NCT03770988</nct_id>
  </id_info>
  <brief_title>A Trial to Evaluate the Efficacy of Poziotinib, Pan HER Inhibitor in Recurrent/Metastatic Esophageal Cancer (R/M ESCC)</brief_title>
  <official_title>A Single Arm Phase II Trial to Evaluate the Efficacy of Poziotinib, Pan HER Inhibitor in Recurrent/Metastatic Esophageal Cancer (R/M ESCC)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Yonsei University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Yonsei University</source>
  <oversight_info>
    <has_dmc>No</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>
      Esophageal cancer is the sixth most common cause of cancer deaths worldwide. Esophageal&#xD;
      adenocarcinoma has become more common in Western countries. In many Asian countries, however,&#xD;
      Esophageal Squamous Cell Carcinoma (ESCC) represents the most common esophageal cancer. In&#xD;
      palliative chemotherapy for metastatic or recurrent ESCC, A combination of 5-fluorouracil and&#xD;
      platinum was prescribed as a standard treatment for about 20 years. With this traditional&#xD;
      regimen, the median progression free survival is approximately 7 months, and 1-year survival&#xD;
      rate is reported to be 34%. Combinations of taxane and anthracycline are also considerable,&#xD;
      but also shows the median survival less than one year. Though cytotoxic chemotherapy is&#xD;
      current main treatment option, molecularly targeted agents are recently incorporated to&#xD;
      improve survival in ESCC. There is a strong rationale for investigation of biologic agents&#xD;
      targeting Epithelial Growth Factor Receptor (EGFR) family in ESCC. EGFR is frequently&#xD;
      overexpressed in esophageal cancer and is known to be associated with poor prognosis. Several&#xD;
      EGFR tyrosine kinase inhibitors (TKIs) have been studied in esophageal cancer subjects and&#xD;
      have shown clinical effects. In a recent Phase II trial using dacomitinib, pan-human&#xD;
      epidermal growth receptor TKI, Partial response was observed in 10 of the 49 esophageal&#xD;
      cancer subjects, with a response rate of 20.8%.&#xD;
&#xD;
      Based on notable rationale in exploring impact of EGFR inhibition, we suggest multicenter&#xD;
      phase II study to determine antitumor activity and safety of a other potent pan-HER&#xD;
      inhibitor, Poziotinib in Esophageal Squamous cell carcinoma.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">April 1, 2019</start_date>
  <completion_date type="Anticipated">August 31, 2020</completion_date>
  <primary_completion_date type="Anticipated">August 31, 2020</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</measure>
    <time_frame>every 8 weeks, assessed up to 100 weeks</time_frame>
    <description>Objective Response Rate using RECIST 1.1</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>From date of randomization until date of death from any cause, whichever came first, assessed up to 100 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival</measure>
    <time_frame>From date of randomization until date of death from any cause, whichever came first, assessed up to 100 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response</measure>
    <time_frame>From date of randomization until date of death from any cause, whichever came first, assessed up to 100 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety assessed by incidence of treatment-emergent adverse events</measure>
    <time_frame>up to 100 weeks</time_frame>
    <description>To evaluate the safety of Poziotinib, pan HER inhibitor in recurrent/metastatic esophageal cancer</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">49</enrollment>
  <condition>Inoperable or Recurrent or Metastatic Esophageal Squamous Carcinoma</condition>
  <arm_group>
    <arm_group_label>poziotinib single arm study</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single Arm study</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Treatment with Poziotinib</intervention_name>
    <description>Treatment with Poziotinib</description>
    <arm_group_label>poziotinib single arm study</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Histologically confirmed esophageal squamous cell carcinoma (Includes cases with&#xD;
             pathologic findings with clinical course comparable to squamous cell carcinoma. For&#xD;
             example, undifferentiated carcinoma)&#xD;
&#xD;
          2. Diseases that can not achieve curative aim with radical surgery, radiation, or&#xD;
             chemo-radiotherapy. Previous palliative chemotherapy including platinum-based agents&#xD;
             for advanced or recurrent esophageal squamous cell carcinoma (If the disease&#xD;
             progresses within 6 months after the curative platinum-based chemotherapy or disease&#xD;
             progresses within 6 months after last adjuvant chemotherapy, it is considered to be&#xD;
             the previous palliative chemotherapy.&#xD;
&#xD;
          3. Have measurable disease based on RECIST 1.1.&#xD;
&#xD;
          4. Be 20 years of age on day of signing informed consent.&#xD;
&#xD;
          5. Performance status of 0 or 1 on the Eastern Cooperative Oncology Group Performance&#xD;
             Scale.&#xD;
&#xD;
          6. Demonstrate adequate organ function&#xD;
&#xD;
          7. Absolute Neutrophil Count ≥ 1500/μL&#xD;
&#xD;
          8. Platelet Count ≥100,000/μL&#xD;
&#xD;
          9. Hemoglobin ≥ 9.0 g/dL&#xD;
&#xD;
         10. Serum creatinine ≤&#xD;
&#xD;
         11. Serum bilirubin ≤ 1.5 x ULN&#xD;
&#xD;
         12. AST, ALT ≤ 1.5 x ULN (with liver metastasis ≤ 5.0 x ULN)&#xD;
&#xD;
         13. Be willing and able to provide written informed consent/assent for the trial.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Without measurable lesion based on RECIST 1.1&#xD;
&#xD;
          2. Has received prior therapy with EGFR/HER2 directed therapy.&#xD;
&#xD;
          3. Has history of intestinal obstruction or recent bleeding (subjects with clinically&#xD;
             significant hemorrhagic or clotting events within the past 6 months)&#xD;
&#xD;
          4. Pregnant or lactating women&#xD;
&#xD;
          5. Women who have not received a baseline pregnancy test or have a positive result. (A&#xD;
             woman who has not undergone a previous hysterectomy, or history of amenorrhea of more&#xD;
             than 12 months, or undergone bilateral oophorectomy is considered to be a non-pregnant&#xD;
             menopausal woman.)&#xD;
&#xD;
          6. Male or reproductive women who are not willing to use contraception during the trial&#xD;
&#xD;
          7. Has a known additional malignancy that is progressing or requires active treatment&#xD;
             within 3 years. (Except skin basal cell carcinoma, cervix epithelial carcinoma in&#xD;
             situ, Superficial bladder cancer)&#xD;
&#xD;
          8. Subjective who is likely to interfere with the understanding of the written consent or&#xD;
             influence the compliance of the trial medication. Patients with a history of&#xD;
             uncontrolled seizures, central nervous system disorders or psychiatric disorders that&#xD;
             are considered clinically significant by the investigator&#xD;
&#xD;
          9. Has stable LVEF of less than 50%&#xD;
&#xD;
         10. Received organ transplants that require immunosuppressive therapy&#xD;
&#xD;
         11. Has un-controlled active infectious disease.&#xD;
&#xD;
         12. Has symptomatic central nerve system metastasis (Except in case of discontinuation of&#xD;
             corticosteroids at least 2 weeks before clinical trials and radiologic and&#xD;
             neurologically stable cases over 4 weeks)&#xD;
&#xD;
         13. Has known history of, or any evidence of active, non-infectious pneumonitis.&#xD;
&#xD;
         14. Has New York Heart Association, NYHA class III or IV Heart failure, un-controlled&#xD;
             hypertension&#xD;
&#xD;
         15. Experienced unstable angina or myocardial infarction within the last 6 months&#xD;
&#xD;
         16. Has un-controlled arrhythmia or judged to have clinically significant cardiovascular&#xD;
             abnormalities by investigators&#xD;
&#xD;
         17. Incapability of Oral ingestion and digestion.&#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_contact>
    <last_name>Hye Ryun Kim, MD</last_name>
    <phone>82 2 2228 8125</phone>
    <email>nobleg@yuhs.ac</email>
  </overall_contact>
  <location>
    <facility>
      <name>Severance Hospital</name>
      <address>
        <city>Seoul</city>
        <zip>03722</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <contact>
      <last_name>Hye Ryun Kim, MD</last_name>
      <phone>82 2 2228 8125</phone>
      <email>nobleg@yuhs.ac</email>
    </contact>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <verification_date>February 2019</verification_date>
  <study_first_submitted>August 14, 2018</study_first_submitted>
  <study_first_submitted_qc>December 7, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 10, 2018</study_first_posted>
  <last_update_submitted>February 20, 2019</last_update_submitted>
  <last_update_submitted_qc>February 20, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">February 22, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>esophageal squamous carcinoma</keyword>
  <keyword>poziotinib</keyword>
  <keyword>pan-HER inhibitor</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Esophageal Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Squamous Cell</mesh_term>
    <mesh_term>Recurrence</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/NCT03770988
org study id: 4-2017-1193
nct id: NCT03770988
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Esophageal cancer is the sixth most common cause of cancer deaths worldwide. Esophageal
      adenocarcinoma has become more common in Western countries. In many Asian countries, however,
      Esophageal Squamous Cell Carcinoma (ESCC) represents the most common esophageal cancer. In
      palliative chemotherapy for metastatic or recurrent ESCC, A combination of 5-fluorouracil and
      platinum was prescribed as a standard treatment for about 20 years. With this traditional
      regimen, the median progression free survival is approximately 7 months, and 1-year survival
      rate is reported to be 34%. Combinations of taxane and anthracycline are also considerable,
      but also shows the median survival less than one year. Though cytotoxic chemotherapy is
      current main treatment option, molecularly targeted agents are recently incorporated to
      improve survival in ESCC. There is a strong rationale for investigation of biologic agents
      targeting Epithelial Growth Factor Receptor (EGFR) family in ESCC. EGFR is frequently
      overexpressed in esophageal cancer and is known to be associated with poor prognosis. Several
      EGFR tyrosine kinase inhibitors (TKIs) have been studied in esophageal cancer subjects and
      have shown clinical effects. In a recent Phase II trial using dacomitinib, pan-human
      epidermal growth receptor TKI, Partial response was observed in 10 of the 49 esophageal
      cancer subjects, with a response rate of 20.8%.

      Based on notable rationale in exploring impact of EGFR inhibition, we suggest multicenter
      phase II study to determine antitumor activity and safety of a other potent pan-HER
      inhibitor, Poziotinib in Esophageal Squamous cell carcinoma.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Objective Response Rate
time frame: every 8 weeks, assessed up to 100 weeks
description: Objective Response Rate using RECIST 1.1
measure: Overall Survival
time frame: From date of randomization until date of death from any cause, whichever came first, assessed up to 100 months
measure: Progression Free Survival
time frame: From date of randomization until date of death from any cause, whichever came first, assessed up to 100 months
measure: Duration of Response
time frame: From date of randomization until date of death from any cause, whichever came first, assessed up to 100 months
measure: Safety assessed by incidence of treatment-emergent adverse events
time frame: up to 100 weeks
description: To evaluate the safety of Poziotinib, pan HER inhibitor in recurrent/metastatic esophageal cancer
arm group label: poziotinib single arm study
arm group type: Experimental
description: Single Arm study
intervention type: Drug
intervention name: Treatment with Poziotinib
description: Treatment with Poziotinib
arm group label: poziotinib single arm study
criteria: 
gender: All
minimum age: 20 Years
maximum age: N/A
healthy volunteers: No
last name: Hye Ryun Kim, MD
phone: 82 2 2228 8125
email: nobleg@yuhs.ac
facility: 
contact: 
country: Korea, Republic of
responsible party type: Sponsor
mesh term: Esophageal Neoplasms
mesh term: Carcinoma, Squamous Cell
mesh term: Recurrence