<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/NCT04454476</url>
  </required_header>
  <id_info>
    <org_study_id>VICC GI 2049</org_study_id>
    <nct_id>NCT04454476</nct_id>
  </id_info>
  <brief_title>Reversal of Preneoplastic Metaplasia in the Stomach With MEK Inhibitor</brief_title>
  <official_title>Reversal of Preneoplastic Metaplasia in the Stomach With MEK Inhibitor Treatment</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Vanderbilt-Ingram Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Vanderbilt-Ingram Cancer Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a study of the safety and effectiveness of Trametinib treatment in patients who have&#xD;
      received successful endoscopic submucosal resection of a Stage I gastric cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Objectives:&#xD;
&#xD;
        -  To evaluate the efficacy of Trametinib in reversing metaplasia in participants with&#xD;
           Stage 1 gastric cancer&#xD;
&#xD;
        -  To evaluate the safety of Trametinibin in Stage I gastric cancer patients&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">November 9, 2022</start_date>
  <completion_date type="Anticipated">May 2025</completion_date>
  <primary_completion_date type="Anticipated">May 2024</primary_completion_date>
  <phase>Phase 1</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>Effectiveness of Trametinib in reversing metaplasia: changes in cell lineages</measure>
    <time_frame>About 12 months</time_frame>
    <description>The ability of Trametinib treatment to decrease the presence of metaplastic cell lineages in biopsies of the lining of the stomach, while also allowing the return of normal cell lineages (i.e. acid-secreting parietal cells). Cell lineages will be identified by immunostaining of tissue sections from biopsies.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Safety of Trametinib treatment: adverse events</measure>
    <time_frame>About 12 weeks</time_frame>
    <description>Assessment of side effects induced during or after treatment with Trametinib.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">15</enrollment>
  <condition>Gastric Cancer</condition>
  <condition>Metaplasia</condition>
  <condition>Stage I Gastric Cancer</condition>
  <condition>Initial-onset Gastric Cancer</condition>
  <arm_group>
    <arm_group_label>Trametinib treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Trametinib treatment</intervention_name>
    <description>1 mg taken by mouth once a day for 14 days</description>
    <arm_group_label>Trametinib treatment</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Endoscopy</intervention_name>
    <description>A tiny camera on the end of a long, flexible tube will be used to examine the stomach and take biopsies.</description>
    <arm_group_label>Trametinib treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Primary registration&#xD;
&#xD;
          -  Person having intact stomach after treatment of early gastric cancer or gastric&#xD;
             adenoma&#xD;
&#xD;
          -  Person whose treated gastric cancer histological type is intestinal type.&#xD;
&#xD;
          -  Person whose treated gastric cancer or gastric adenoma was curatively resected.&#xD;
&#xD;
          -  Person who does not have symptoms of gastric cancer recurrence.&#xD;
&#xD;
          -  Person who can declare agreement for enrollment by understanding the study and signing&#xD;
             the informed consent document after hearing the explanation.&#xD;
&#xD;
          -  Person who can visit the hospital in accordance with the schedule.&#xD;
&#xD;
        Secondary registration&#xD;
&#xD;
          -  Person who has gastric atrophy at endoscopy.&#xD;
&#xD;
          -  Person who does not have symptoms of gastric cancer recurrence by endoscopy.&#xD;
&#xD;
          -  Person who has intestinal metaplasia in stomach, histologically confirmed in biopsy&#xD;
             specimens taken under endoscopy within 8 weeks prior to taking MEK inhibitor,&#xD;
             Trametinib.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Person whose treated gastric cancer was diffuse or signet ring cancer.&#xD;
&#xD;
          -  Person whose treated gastric cancer or gastric adenoma was not curatively resected.&#xD;
&#xD;
          -  Person who has the history of other malignant disease.&#xD;
&#xD;
          -  Person who had a significant improvement in metaplasia after eradication therapy for&#xD;
             Helicobacter pylori within one year.&#xD;
&#xD;
          -  Person who had plan of eradication Helicobacter pylori in 1 year 9 months&#xD;
&#xD;
          -  Person who has history of previous Trametinib or other MEK inhibitor use.&#xD;
&#xD;
          -  Person who has history of hypersensitivity to excipients.&#xD;
&#xD;
          -  Person who entered clinical trial and took investigational new drug within 12 weeks.&#xD;
&#xD;
          -  Presence of active infection other than chronic gastritis.&#xD;
&#xD;
          -  Cardiac conditions as follows:&#xD;
&#xD;
               -  Uncontrolled hypertension (BP&gt;=150/95 mm Hg despite medical therapy)&#xD;
&#xD;
               -  Acute myocardial infection within 6 months prior to starting treatment&#xD;
&#xD;
               -  Uncontrolled Angina (Canadian Cardiovascular Society grade II-IV even after&#xD;
                  medication)&#xD;
&#xD;
               -  Symptomatic heart failure NYHA Class II-IV&#xD;
&#xD;
               -  &lt;45% in the past&#xD;
&#xD;
               -  Severe valvular disease&#xD;
&#xD;
               -  &lt;55% at present&#xD;
&#xD;
               -  Atrial fibrilation in ECG with BPM=&gt;100 Laboratory values as listed below (SI&#xD;
                  units) Absolute Neutrophil Count &lt;1.5x10A9/L (1500 per mm3) Platelets &lt;100x10A9/L&#xD;
                  (100,000 per mm3) Hemoglobin&lt;=9.0 g /dL Serum creatinine &gt;1.5 X upper limit of&#xD;
                  normal (ULN) Serum bilirubin &gt;1.5 x ULN AST or ALT &gt; 2.5 x ULN&#xD;
&#xD;
        Ophthalmological conditions as follows:&#xD;
&#xD;
        Current or past history of retinal pigment epithelial detachment (RPED)/central serous&#xD;
        retinopathy (CSR) or retinal vein occlusion Intraocular pressure (IOP) &gt; 21 mmHg or&#xD;
        uncontrolled glaucoma (irrespective of IOP)&#xD;
&#xD;
        Male or female patients of reproductive potential and, as judged by the investigator, are&#xD;
        not employing an effective method of birth control and pregnant female.&#xD;
&#xD;
        Breast feeding female Have refractory nausea and vomiting , chronic gastrointestinal&#xD;
        diseases (e.g . inflammatory bowel disease), or significant bowel resection that would&#xD;
        adversely affect the absorption / bioavailability of the orally administered study&#xD;
        medication.&#xD;
&#xD;
        Person who has history of hyperrefractory for Trametinib methyl sulfoxide Person who has&#xD;
        pneumonia under chest X-ray. Have evidence of any other significant clinical disorder or&#xD;
        laboratory finding that, as judgedby the investigator, makes it undesirable for the patient&#xD;
        to participate in the study.&#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>James Goldenring, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Vanderbilt Medical Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>James Goldenring, MD</last_name>
    <phone>615-936-3726</phone>
    <email>jim.goldenring@vumc.org</email>
  </overall_contact>
  <location>
    <facility>
      <name>Nagasaki University Hospital</name>
      <address>
        <city>Nagasaki</city>
        <country>Japan</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Naoyuki Yamaguchi</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Nihon University School of Medicine</name>
      <address>
        <city>Tokyo</city>
        <country>Japan</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Takuji Gotoda</last_name>
      <email>takujigotoda@yahoo.com.jp</email>
    </contact>
    <investigator>
      <last_name>Takuji Gotoda</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University of Tokyo Medical Center</name>
      <address>
        <city>Tokyo</city>
        <country>Japan</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sachiyo Nomura</last_name>
      <email>snomura-gi@umin.ac.jp</email>
    </contact>
    <investigator>
      <last_name>Sachiyo Nomura</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Japan</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>June 24, 2020</study_first_submitted>
  <study_first_submitted_qc>June 30, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 1, 2020</study_first_posted>
  <last_update_submitted>July 6, 2023</last_update_submitted>
  <last_update_submitted_qc>July 6, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 10, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Vanderbilt-Ingram Cancer Center</investigator_affiliation>
    <investigator_full_name>James Goldenring</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Stomach Neoplasms</mesh_term>
    <mesh_term>Metaplasia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Trametinib</mesh_term>
  </intervention_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/NCT04454476
org study id: VICC GI 2049
nct id: NCT04454476
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
This is a study of the safety and effectiveness of Trametinib treatment in patients who have
      received successful endoscopic submucosal resection of a Stage I gastric cancer.
Objectives:

        -  To evaluate the efficacy of Trametinib in reversing metaplasia in participants with
           Stage 1 gastric cancer

        -  To evaluate the safety of Trametinibin in Stage I gastric cancer patients
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Effectiveness of Trametinib in reversing metaplasia: changes in cell lineages
time frame: About 12 months
description: The ability of Trametinib treatment to decrease the presence of metaplastic cell lineages in biopsies of the lining of the stomach, while also allowing the return of normal cell lineages (i.e. acid-secreting parietal cells). Cell lineages will be identified by immunostaining of tissue sections from biopsies.
measure: Safety of Trametinib treatment: adverse events
time frame: About 12 weeks
description: Assessment of side effects induced during or after treatment with Trametinib.
arm group label: Trametinib treatment
arm group type: Experimental
intervention type: Drug
intervention name: Trametinib treatment
description: 1 mg taken by mouth once a day for 14 days
arm group label: Trametinib treatment
intervention type: Procedure
intervention name: Endoscopy
description: A tiny camera on the end of a long, flexible tube will be used to examine the stomach and take biopsies.
arm group label: Trametinib treatment
criteria: 
gender: All
minimum age: 20 Years
maximum age: N/A
healthy volunteers: No
last name: James Goldenring, MD
role: Principal Investigator
affiliation: Vanderbilt Medical Center
last name: James Goldenring, MD
phone: 615-936-3726
email: jim.goldenring@vumc.org
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
country: Japan
responsible party type: Principal Investigator
investigator affiliation: Vanderbilt-Ingram Cancer Center
investigator full name: James Goldenring
investigator title: Principal Investigator
mesh term: Stomach Neoplasms
mesh term: Metaplasia
mesh term: Trametinib
sharing ipd: No