<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/NCT04447092</url>
  </required_header>
  <id_info>
    <org_study_id>H-2003-235-1115</org_study_id>
    <nct_id>NCT04447092</nct_id>
  </id_info>
  <brief_title>Pembrolizumab Plus Chemotherapy in 1st Line Treatment of Pancreatic Cancer</brief_title>
  <official_title>Biomarker-oriented Study of Pembrolizumab in Combination With Chemotherapy in Chemotherapy -naïve Advanced Pancreatic Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Seoul National University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Seoul National University Hospital</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>
      This is an open-label, phase 2 study of Pembrolizumab in combination with chemotherapy in&#xD;
      chemotherapy-naïve advanced pancreatic cancer&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      -  In unresectable advanced pancreatic cancer, palliative chemotherapy (mainly&#xD;
           Gemcitabine/nab-Paclitaxel or FOLFIRINOX) is the mainstay of treatment. Regardless of&#xD;
           the choice of first-line therapy, more than half of the patients with&#xD;
           advanced/metastatic disease will progress within six months and will not survive more&#xD;
           than one year.&#xD;
&#xD;
        -  Immune cells (IC) are a significant part of the pancreatic tumor-associated stroma and&#xD;
           play a fundamental part in maintaining a non-immunogenic and immuno-suppressive&#xD;
           environment.&#xD;
&#xD;
        -  IO (Immuno-Oncology drug) monotherapy is not effective in advanced pancreatic cancer;&#xD;
           therefore, we need more active combination regimens including IO/IO or IO/chemotherapy,&#xD;
           etc. Furthermore, we need biomarker study to uncover which population is an optimal&#xD;
           target for this IO-based treatment strategy.&#xD;
&#xD;
        -  Based on these rationale, we plan to conduct an open-label, phase 2 study to explore&#xD;
           biomarkers and evaluate the safety and efficacy of the pembrolizumab/chemotherapy&#xD;
           combination in an advanced pancreatic cancer primary environment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">July 1, 2020</start_date>
  <completion_date type="Anticipated">December 31, 2024</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2023</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel 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>8 weeks</time_frame>
    <description>The percentage of patients whose optimal response achieves CR or PR between the initial response assessment and the time between treatment termination or intermediate dropout due to any cause</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival</measure>
    <time_frame>8 weeks</time_frame>
    <description>Time from enroll until disease progression or death</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response</measure>
    <time_frame>8 weeks</time_frame>
    <description>Time from enroll untill disease progression or death in patients whose optimal response achieves CR or PR</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease control rate</measure>
    <time_frame>8 weeks</time_frame>
    <description>The percentage of patients who have achieved complete response, partial response and stable disease</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>8 weeks</time_frame>
    <description>Time from enroll until death from any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immune-related response</measure>
    <time_frame>8 weeks</time_frame>
    <description>RECIST 1.1, ir response</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">77</enrollment>
  <condition>Pancreatic Cancer</condition>
  <condition>Chemotherapy Effect</condition>
  <arm_group>
    <arm_group_label>Gemcitabine/Nab-paclitaxel</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Gemcitabine/Nab-paclitaxel + pembrolizumab</description>
  </arm_group>
  <arm_group>
    <arm_group_label>FOLFIRINOX</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>FOLFIRINOX + pembrolizumab</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Gemcitabine</intervention_name>
    <description>Gemcitabine 1000 mg/m2 iv D1, 8, 15 (every 4 weeks)</description>
    <arm_group_label>Gemcitabine/Nab-paclitaxel</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nab-paclitaxel</intervention_name>
    <description>Nab-paclitaxel 125 mg/m2 iv D1, 8, 15 (every 4 weeks)</description>
    <arm_group_label>Gemcitabine/Nab-paclitaxel</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pembrolizumab</intervention_name>
    <description>Pembrolizumab ( 200 ) mg iv D1 (every 3 weeks)</description>
    <arm_group_label>FOLFIRINOX</arm_group_label>
    <arm_group_label>Gemcitabine/Nab-paclitaxel</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Oxaliplatin</intervention_name>
    <description>Oxaliplatin 65 mg/m2 iv over 2 hours D1 (every 2 weeks)</description>
    <arm_group_label>FOLFIRINOX</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Leucovorin</intervention_name>
    <description>Leucovorin 400 mg/m2 iv D1 (every 2 weeks)</description>
    <arm_group_label>FOLFIRINOX</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Irinotecan</intervention_name>
    <description>Irinotecan 140 mg/m2 iv over 1.5 hours D1 (every 2 weeks)</description>
    <arm_group_label>FOLFIRINOX</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>5FU</intervention_name>
    <description>5-FU 2400 mg/m2 iv over 46 hours D1 (every 2 weeks)</description>
    <arm_group_label>FOLFIRINOX</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male/female participants who are at least 18 years of age on the day of signing&#xD;
             informed consent&#xD;
&#xD;
          2. Histologically confirmed diagnosis of unresectable, recurrent, or metastatic&#xD;
             pancreatic cancer&#xD;
&#xD;
          3. Not pregnant, not breasfeeding, and agree to use proper contraception,&#xD;
&#xD;
          4. Chemotherapy-naïve for advanced pancreatic cancer (previous adjuvant chemotherapy is&#xD;
             allowed)&#xD;
&#xD;
          5. Have measurable disease based on RECIST 1.1.&#xD;
&#xD;
          6. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.&#xD;
&#xD;
          7. Have adequate organ function&#xD;
&#xD;
               -  Haemoglobin ≥ 9.0 g/dL&#xD;
&#xD;
               -  Absolute neutrophil count (ANC) 1.5 (or 1.0) x (&gt; 1500 per mm3)&#xD;
&#xD;
               -  Platelet count ≥ 100 x 109/L (&gt;75,000 per mm3)&#xD;
&#xD;
               -  Serum creatinine CL&gt;30 mL/min by the Cockcroft-Gault formula or serum creatinine&#xD;
                  ≤1.5 × ULN&#xD;
&#xD;
               -  Serum bilirubin ≤ 1.5 x ULN&#xD;
&#xD;
               -  AST (SGOT)/ALT (SGPT) ≤ 2.5 x ULN unless liver metastases are present, in which&#xD;
                  case it must be ≤ 5x ULN&#xD;
&#xD;
               -  International normalized ratio (INR) or Prothrombin time (PT), activated partial&#xD;
                  thromboplastin time (aPTT) ≤1.5 × ULN unless participant is receiving&#xD;
                  anticoagulant therapy&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. A WOCBP who has a positive urine pregnancy test within 72 hours prior to allocation&#xD;
&#xD;
          2. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with&#xD;
             an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4,&#xD;
             OX 40, CD137).&#xD;
&#xD;
          3. Has received prior systemic anti-cancer therapy including investigational agents&#xD;
             within 4 weeks&#xD;
&#xD;
          4. Has received prior radiotherapy within 2 weeks of start of study treatment.&#xD;
&#xD;
          5. Has received a live vaccine within 30 days prior to the first dose of study drug.&#xD;
&#xD;
          6. Is currently participating in or has participated in a study of an investigational&#xD;
             agent or has used an investigational device&#xD;
&#xD;
          7. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy&#xD;
             (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of&#xD;
             immunosuppressive therapy within 7 days prior to the first dose of study drug.&#xD;
&#xD;
          8. Has a known additional malignancy that is progressing or has required active treatment&#xD;
             within the past 3 years.&#xD;
&#xD;
          9. Has known active CNS metastases and/or carcinomatous meningitis.&#xD;
&#xD;
         10. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.&#xD;
&#xD;
         11. Has active autoimmune disease that has required systemic treatment in the past 2 years&#xD;
&#xD;
         12. Has a history of (non-infectious) pneumonitis that required steroids or has current&#xD;
             pneumonitis.&#xD;
&#xD;
         13. Has an active infection requiring systemic therapy.&#xD;
&#xD;
         14. Has a known history of Human Immunodeficiency Virus (HIV).&#xD;
&#xD;
         15. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg]&#xD;
             reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is&#xD;
             detected) infection.&#xD;
&#xD;
         16. Has a known history of active TB (Bacillus Tuberculosis).&#xD;
&#xD;
         17. Has a history or current evidence of any condition, therapy, or laboratory abnormality&#xD;
             that might confound the results of the study, interfere with the subject's&#xD;
             participation for the full duration of the study, or is not in the best interest of&#xD;
             the subject to participate, in the opinion of the treating investigator.&#xD;
&#xD;
         18. Has known psychiatric or substance abuse disorders that would interfere with&#xD;
             cooperation with the requirements of the trial.&#xD;
&#xD;
         19. Is pregnant or breastfeeding, or expecting to conceive or father children within the&#xD;
             projected duration of the study, starting with the screening visit through 120 days&#xD;
             after the last dose of trial treatment.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Do-Youn Oh, M.D., PhD.</last_name>
    <role>Study Director</role>
    <affiliation>Seoul National University Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Seoul National University Hospital</name>
      <address>
        <city>Seoul</city>
        <zip>110-744</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>June 23, 2020</study_first_submitted>
  <study_first_submitted_qc>June 23, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 25, 2020</study_first_posted>
  <last_update_submitted>April 10, 2023</last_update_submitted>
  <last_update_submitted_qc>April 10, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 12, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Seoul National University Hospital</investigator_affiliation>
    <investigator_full_name>Do-Youn Oh</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>Pancreatic Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leucovorin</mesh_term>
    <mesh_term>Paclitaxel</mesh_term>
    <mesh_term>Gemcitabine</mesh_term>
    <mesh_term>Pembrolizumab</mesh_term>
    <mesh_term>Oxaliplatin</mesh_term>
    <mesh_term>Irinotecan</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/NCT04447092
org study id: H-2003-235-1115
nct id: NCT04447092
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This is an open-label, phase 2 study of Pembrolizumab in combination with chemotherapy in
      chemotherapy-naïve advanced pancreatic cancer
-  In unresectable advanced pancreatic cancer, palliative chemotherapy (mainly
           Gemcitabine/nab-Paclitaxel or FOLFIRINOX) is the mainstay of treatment. Regardless of
           the choice of first-line therapy, more than half of the patients with
           advanced/metastatic disease will progress within six months and will not survive more
           than one year.

        -  Immune cells (IC) are a significant part of the pancreatic tumor-associated stroma and
           play a fundamental part in maintaining a non-immunogenic and immuno-suppressive
           environment.

        -  IO (Immuno-Oncology drug) monotherapy is not effective in advanced pancreatic cancer;
           therefore, we need more active combination regimens including IO/IO or IO/chemotherapy,
           etc. Furthermore, we need biomarker study to uncover which population is an optimal
           target for this IO-based treatment strategy.

        -  Based on these rationale, we plan to conduct an open-label, phase 2 study to explore
           biomarkers and evaluate the safety and efficacy of the pembrolizumab/chemotherapy
           combination in an advanced pancreatic cancer primary environment.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Objective Response Rate
time frame: 8 weeks
description: The percentage of patients whose optimal response achieves CR or PR between the initial response assessment and the time between treatment termination or intermediate dropout due to any cause
measure: Progression-free survival
time frame: 8 weeks
description: Time from enroll until disease progression or death
measure: Duration of response
time frame: 8 weeks
description: Time from enroll untill disease progression or death in patients whose optimal response achieves CR or PR
measure: Disease control rate
time frame: 8 weeks
description: The percentage of patients who have achieved complete response, partial response and stable disease
measure: Overall survival
time frame: 8 weeks
description: Time from enroll until death from any cause
measure: Immune-related response
time frame: 8 weeks
description: RECIST 1.1, ir response
arm group label: Gemcitabine/Nab-paclitaxel
arm group type: Experimental
description: Gemcitabine/Nab-paclitaxel + pembrolizumab
arm group label: FOLFIRINOX
arm group type: Experimental
description: FOLFIRINOX + pembrolizumab
intervention type: Drug
intervention name: Gemcitabine
description: Gemcitabine 1000 mg/m2 iv D1, 8, 15 (every 4 weeks)
arm group label: Gemcitabine/Nab-paclitaxel
intervention type: Drug
intervention name: Nab-paclitaxel
description: Nab-paclitaxel 125 mg/m2 iv D1, 8, 15 (every 4 weeks)
arm group label: Gemcitabine/Nab-paclitaxel
intervention type: Drug
intervention name: Pembrolizumab
description: Pembrolizumab ( 200 ) mg iv D1 (every 3 weeks)
arm group label: FOLFIRINOX
arm group label: Gemcitabine/Nab-paclitaxel
intervention type: Drug
intervention name: Oxaliplatin
description: Oxaliplatin 65 mg/m2 iv over 2 hours D1 (every 2 weeks)
arm group label: FOLFIRINOX
intervention type: Drug
intervention name: Leucovorin
description: Leucovorin 400 mg/m2 iv D1 (every 2 weeks)
arm group label: FOLFIRINOX
intervention type: Drug
intervention name: Irinotecan
description: Irinotecan 140 mg/m2 iv over 1.5 hours D1 (every 2 weeks)
arm group label: FOLFIRINOX
intervention type: Drug
intervention name: 5FU
description: 5-FU 2400 mg/m2 iv over 46 hours D1 (every 2 weeks)
arm group label: FOLFIRINOX
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Do-Youn Oh, M.D., PhD.
role: Study Director
affiliation: Seoul National University Hospital
facility: 
country: Korea, Republic of
responsible party type: Principal Investigator
investigator affiliation: Seoul National University Hospital
investigator full name: Do-Youn Oh
investigator title: Professor
mesh term: Pancreatic Neoplasms
mesh term: Leucovorin
mesh term: Paclitaxel
mesh term: Gemcitabine
mesh term: Pembrolizumab
mesh term: Oxaliplatin
mesh term: Irinotecan
sharing ipd: No