<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/NCT03254004</url>
  </required_header>
  <id_info>
    <org_study_id>2017-08-032</org_study_id>
    <nct_id>NCT03254004</nct_id>
  </id_info>
  <brief_title>Postoperative Pembrolizumab for the Patients Who Have Solid Predominant or Micropapillary Lung Adenocarcinoma With Pathologic Stage I and Primary Tumor Than 4 cm</brief_title>
  <official_title>Postoperative Pembrolizumab for the Patients Who Have Solid Predominant or Micropapillary Lung Adenocarcinoma With Pathologic Stage I and Primary Tumor Than 4 cm</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Samsung Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Samsung Medical Center</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>
      A single center, open-label, single arm study in patients who have solid or micropapillary&#xD;
      adenocarcinoma with pathologic stage I and primary tumor no more than 4 cm. Pembrolizumab 200&#xD;
      mg every 3 weeks&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a single center, open-label, single arm study in patients who have solid or&#xD;
      micropapillary adenocarcinoma with pathologic stage I and primary tumor no more than 4 cm.&#xD;
      Patients will be treated with pembrolizumab 200 mg every 3 weeks till 1 year or disease&#xD;
      recurrence or intolerable toxicity.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">October 8, 2018</start_date>
  <completion_date type="Anticipated">November 30, 2021</completion_date>
  <primary_completion_date type="Anticipated">March 30, 2021</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>
    <intervention_model_description>Pembrolizumab 200mg injection</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>To assess the improvement of disease-free survival rate by adjuvant therapy with pembrolizumab for solid or micropapillary adenocarcinoma with pathologic stage I and tumor size no more than 4 cm.</measure>
    <time_frame>up to 16 times. (screening, every 4 cycles during the study, every 3 months till 1 year since the study treatment, and then every 4 months afterward till 2 years and thereafter every 6 months till 3 years)</time_frame>
    <description>RECIST V1.1</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">70</enrollment>
  <condition>Lung Adenocarcinoma, Stage I</condition>
  <arm_group>
    <arm_group_label>single arm: pembrolizumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>pembrolizumab 200 mg every 3 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pembrolizumab</intervention_name>
    <description>pembrolizumab 200 mg every 3 weeks till 1 year or disease recurrence or intolerable toxicity.</description>
    <arm_group_label>single arm: pembrolizumab</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Primary lung adenocarcinoma patients with stage I and less than 4 centimeter of&#xD;
             primary tumor, whose tumor should be solid-predominant or micropapillary (&gt;5%) by&#xD;
             postsurgical pathological examination.&#xD;
&#xD;
               -  Note: The specific methods and principles of pathology results follow the WHO's&#xD;
                  pathology guidelines. The institution uses diagnostic pathology results from the&#xD;
                  institution.&#xD;
&#xD;
               -  Note: Adenocarcinoma, solid-predominant subtype; This variant shows a major&#xD;
                  component of polygonal tumor cells forming sheets that lack recognizable patterns&#xD;
                  of adenocarcinoma, i.e., acinar, papillary, micropapillary, or lepidic growth. If&#xD;
                  the tumor is 100% solid, intracellular mucin should be present in &gt;5 tumor cells&#xD;
                  in each of two high-power fields, and confirmed with histochemical stains for&#xD;
                  mucin.&#xD;
&#xD;
               -  Note: Adenocarcinoma, micropapillary subtype; This variant has, as a major&#xD;
                  component, tumor cells growing in papillary tufts forming florets that lack&#xD;
                  fibrovascular cores. These may appear detached from and/or connected to alveolar&#xD;
                  walls. The tumor cells are usually small and cuboidal, with variable nuclear&#xD;
                  atypia. Ring-like glandular structures may float within alveolar spaces. Vascular&#xD;
                  and stromal invasion is common. Psammoma bodies may be seen.&#xD;
&#xD;
          2. Be willing and able to provide written informed consent/assent for the trial.&#xD;
&#xD;
          3. No evidence of disease (NED) after surgical resection on baseline tumor imaging (chest&#xD;
             CT, covering up to both adrenals). The following conditions are satisfied with the&#xD;
             condition of the complete ablation(R0):&#xD;
&#xD;
               -  free resection margins proved microscopically&#xD;
&#xD;
               -  no evidence of nodal metastasis by ststematic and radical nodal dissection&#xD;
&#xD;
          4. Be 20 years of age on day of signing informed consent.&#xD;
&#xD;
          5. Be willing to provide tissue from surgical specimen or excisional biopsy of a tumor&#xD;
             lesion.&#xD;
&#xD;
          6. Have a performance status of 0 or 1 on the ECOG Performance Scale.&#xD;
&#xD;
          7. Demonstrate adequate organ function as defined in Table 1, all screening labs should&#xD;
             be performed within 10 days of treatment initiation.&#xD;
&#xD;
             Table 1 Adequate Organ Function Laboratory Values&#xD;
&#xD;
               -  Hematological&#xD;
&#xD;
                    -  Absolute neutrophil count (ANC): ≥1,500 /mcL&#xD;
&#xD;
                    -  Platelets: ≥100,000 / mcL&#xD;
&#xD;
                    -  Hemoglobin: ≥9 g/dL or ≥5.6 mmol/L without transfusion or EPO dependency&#xD;
                       (within 7 days of assessment)&#xD;
&#xD;
               -  Renal&#xD;
&#xD;
                    -  Serum creatinine OR Measured or calculateda creatinine: ≤ 1.5 X upper limit&#xD;
                       of normal (ULN) OR&#xD;
&#xD;
                    -  clearance(GFR can also be used in place of creatinine or CrCl): ≥ 60 mL/min&#xD;
                       for subject with creatinine levels &gt; 1.5 X institutional ULN&#xD;
&#xD;
               -  Hepatic&#xD;
&#xD;
                    -  Serum total bilirubin: ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects&#xD;
                       with total bilirubin levels &gt; 1.5 ULN&#xD;
&#xD;
                    -  AST (SGOT) and ALT (SGPT): ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver&#xD;
                       metastases&#xD;
&#xD;
                    -  Albumin: &gt;2.5 mg/dL&#xD;
&#xD;
               -  Coagulation&#xD;
&#xD;
                    -  International Normalized Ratio (INR) or Prothrombin Time (PT): ≤ 1.5 X ULN&#xD;
                       unless subject is receiving anticoagulant therapy as long as PT or PTT is&#xD;
                       within therapeutic range of intenede use of anticoagulants&#xD;
&#xD;
                    -  Activated Partial Thromboplastin Time (aPTT): ≤1.5 X ULN unless subject is&#xD;
                       receiving anticoagulant therapy as long as PT or PTT is within therapeutic&#xD;
                       range of intenede use of anticoagulants&#xD;
&#xD;
                    -  Creatinine clearance should be calculated per institutional standard.&#xD;
&#xD;
          8. Female subject of childbearing potential should have a negative urine or serum&#xD;
             pregnancy within 72 hours prior to receiving the first dose of study medication. If&#xD;
             the urine test is positive or cannot be confirmed as negative, a serum pregnancy test&#xD;
             will be required.&#xD;
&#xD;
          9. Female subjects of childbearing potential (Section 5.7.2) must be willing to use an&#xD;
             adequate method of contraception as outlined in Section 5.7.2 - Contraception, for the&#xD;
             course of the study through 120 days after the last dose of study medication.&#xD;
&#xD;
               -  Note: Abstinence is acceptable if this is the usual lifestyle and preferred&#xD;
                  contraception for the subject.&#xD;
&#xD;
         10. Male subjects of childbearing potential (Section 5.7.1) must agree to use an adequate&#xD;
             method of contraception as outlined in Section 5.7.1- Contraception, starting with the&#xD;
             first dose of study therapy through 120 days after the last dose of study therapy.&#xD;
&#xD;
               -  Note: Abstinence is acceptable if this is the usual lifestyle and preferred&#xD;
                  contraception for the subject.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Is currently participating and receiving study therapy or has participated in a study&#xD;
             of an investigational agent and received study therapy or used an investigational&#xD;
             device within 4 weeks of the first dose of treatment.&#xD;
&#xD;
          2. Is on chronic systemic steroids. Subjects with asthma that require intermittent use of&#xD;
             bronchodilators, inhaled steroids, or local steroid injections would not be excluded&#xD;
             from the study.&#xD;
&#xD;
          3. Hypersensitivity to pembrolizumab or any of its excipients.&#xD;
&#xD;
          4. Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study&#xD;
             Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events&#xD;
             due to agents administered more than 4 weeks earlier.&#xD;
&#xD;
          5. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy&#xD;
             within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at&#xD;
             baseline) from adverse events due to a previously administered agent.&#xD;
&#xD;
               -  Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and&#xD;
                  may qualify for the study.&#xD;
&#xD;
               -  Note: If subject received major surgery, they must have recovered adequately from&#xD;
                  the toxicity and/or complications from the intervention prior to starting&#xD;
                  therapy.&#xD;
&#xD;
          6. Has a known additional malignancy that is progressing or requires active treatment.&#xD;
             Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the&#xD;
             skin that has undergone potentially curative therapy or in situ cervical cancer.&#xD;
&#xD;
          7. Has known active central nervous system (CNS) metastases and/or carcinomatous&#xD;
             meningitis.&#xD;
&#xD;
          8. Has active autoimmune disease that has required systemic treatment in the past 2 years&#xD;
             (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive&#xD;
             drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid&#xD;
             replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a&#xD;
             form of systemic treatment.&#xD;
&#xD;
          9. Has known history of, or any evidence of active, non-infectious pneumonitis.&#xD;
&#xD;
         10. Has a history of (non-infectious) pneumonitis that required steroids or current&#xD;
             pneumonitis&#xD;
&#xD;
         11. Has an active infection requiring systemic therapy.&#xD;
&#xD;
         12. Has a history or current evidence of any condition, therapy, or laboratory abnormality&#xD;
             that might confound the results of the trial, interfere with the subject's&#xD;
             participation for the full duration of the trial, or is not in the best interest of&#xD;
             the subject to participate, in the opinion of the treating investigator.&#xD;
&#xD;
         13. Has known psychiatric or substance abuse disorders that would interfere with&#xD;
             cooperation with the requirements of the trial.&#xD;
&#xD;
         14. Is pregnant or breastfeeding, or expecting to conceive or father children within the&#xD;
             projected duration of the trial, starting with the pre-screening or screening visit&#xD;
             through 120 days after the last dose of trial treatment.&#xD;
&#xD;
         15. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.&#xD;
&#xD;
         16. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).&#xD;
&#xD;
         17. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA&#xD;
             [qualitative] is detected).&#xD;
&#xD;
         18. Has received a live vaccine within 30 days of planned start of study therapy.&#xD;
&#xD;
               -  Note: Seasonal influenza vaccines for injection are generally inactivated flu&#xD;
                  vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®)&#xD;
                  are live attenuated vaccines, and are not allowed.&#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>jhingook Kim, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Samsung Medical Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>jhingook Kim, MD</last_name>
    <phone>82-10-9933-3483</phone>
    <email>jhingookkim@gmail.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>hyunjung Shin</last_name>
    <phone>82-2-3410-6763</phone>
    <email>hjds.shin@samsung.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Samsung medical centre</name>
      <address>
        <city>Seoul</city>
        <state>Kangnam</state>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>jingook Kim, PhD</last_name>
    </contact>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <verification_date>December 2020</verification_date>
  <study_first_submitted>August 16, 2017</study_first_submitted>
  <study_first_submitted_qc>August 16, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 18, 2017</study_first_posted>
  <last_update_submitted>December 11, 2020</last_update_submitted>
  <last_update_submitted_qc>December 11, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">December 14, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Samsung Medical Center</investigator_affiliation>
    <investigator_full_name>Jhingook Kim, MD</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Adenocarcinoma</mesh_term>
    <mesh_term>Adenocarcinoma of Lung</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pembrolizumab</mesh_term>
  </intervention_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/NCT03254004
org study id: 2017-08-032
nct id: NCT03254004
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
A single center, open-label, single arm study in patients who have solid or micropapillary
      adenocarcinoma with pathologic stage I and primary tumor no more than 4 cm. Pembrolizumab 200
      mg every 3 weeks
This is a single center, open-label, single arm study in patients who have solid or
      micropapillary adenocarcinoma with pathologic stage I and primary tumor no more than 4 cm.
      Patients will be treated with pembrolizumab 200 mg every 3 weeks till 1 year or disease
      recurrence or intolerable toxicity.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Pembrolizumab 200mg injection
primary purpose: Treatment
masking: None (Open Label)
measure: To assess the improvement of disease-free survival rate by adjuvant therapy with pembrolizumab for solid or micropapillary adenocarcinoma with pathologic stage I and tumor size no more than 4 cm.
time frame: up to 16 times. (screening, every 4 cycles during the study, every 3 months till 1 year since the study treatment, and then every 4 months afterward till 2 years and thereafter every 6 months till 3 years)
description: RECIST V1.1
arm group label: single arm: pembrolizumab
arm group type: Experimental
description: pembrolizumab 200 mg every 3 weeks
intervention type: Drug
intervention name: Pembrolizumab
description: pembrolizumab 200 mg every 3 weeks till 1 year or disease recurrence or intolerable toxicity.
arm group label: single arm: pembrolizumab
criteria: 
gender: All
minimum age: 20 Years
maximum age: N/A
healthy volunteers: No
last name: jhingook Kim, MD
role: Principal Investigator
affiliation: Samsung Medical Center
last name: jhingook Kim, MD
phone: 82-10-9933-3483
email: jhingookkim@gmail.com
last name: hyunjung Shin
phone: 82-2-3410-6763
email: hjds.shin@samsung.com
facility: 
status: Recruiting
contact: 
country: Korea, Republic of
responsible party type: Principal Investigator
investigator affiliation: Samsung Medical Center
investigator full name: Jhingook Kim, MD
investigator title: Professor
mesh term: Adenocarcinoma
mesh term: Adenocarcinoma of Lung
mesh term: Pembrolizumab
sharing ipd: Undecided