xml: <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/NCT06001658</url>
    </required_header>
    <id_info>
      <org_study_id>J2390</org_study_id>
      <secondary_id>IRB00371087</secondary_id>
      <nct_id>NCT06001658</nct_id>
    </id_info>
    <brief_title>Perioperative Gemcitabine, Cisplatin, and Pembrolizumab in Potentially Resectable Biliary Tract Cancers</brief_title>
    <official_title>Tumor Microenvironment Features of Response to Perioperative Gemcitabine, Cisplatin, and Pembrolizumab in Potentially Resectable Biliary Tract Cancers</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Merck Sharp &amp; Dohme LLC</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
    </sponsors>
    <source>Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins</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>No</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        The purpose of this study is to determine the safety of peri-operative gemcitabine,&#xD;
        cisplatin, and pembrolizumab in patients with BTC, as well as whether the combination of&#xD;
        gemcitabine, cisplatin, and pembrolizumab (gem/cis/pembro) is feasible and lead to pathologic&#xD;
        responses.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">December 2023</start_date>
    <completion_date type="Anticipated">December 2027</completion_date>
    <primary_completion_date type="Anticipated">December 2027</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>Average minimum Euclidean distance from CD8+ T cells to immunosuppressive tumor-associated macrophages (TAMs) at the per-cell level in patients with a major pathologic response versus pathologic non-responders.</measure>
      <time_frame>4 years</time_frame>
      <description>The evaluable population of this endpoint consist of all patients who receive at least one dose of study drug and have TAMs and CD8 T cell measures at the time of surgery. TAMs being evaluated are the following: immunosuppressive TAMs with high Arginase-1 expression (CD68+CD163+Arg-1hiPDL1-/+), immunosuppressive TAMs with low Arginase-1 expression (CD68+CD163+Arg-1lo PDL1-/+), and less immunosuppressive TAMs (CD68+CD163-HLA-DRhi/CD86hi/PDL1hi)</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Number of participants experiencing grade 3 or above drug-related toxicities</measure>
      <time_frame>4 years</time_frame>
      <description>When calculating the incidence of AEs, each AE (as defined by NCI CTCAE v5.0) will be counted only once for a given subject.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of patients proceeding to surgery without an extended treatment-related delay as a measure of feasibility</measure>
      <time_frame>144 days</time_frame>
      <description>Extended treatment delay is defined as a delay of greater than 60 days of the pre-planned surgical evaluation date, or inability to go to surgery due to an adverse event related to study treatment.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Major pathologic response rate</measure>
      <time_frame>8-12 weeks</time_frame>
      <description>The number of participants with a major pathologic response as defined by ≤ 10% residual viable tumor cells in the resection of the primary tumor and lymph nodes.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>R0 resection rate</measure>
      <time_frame>60 days</time_frame>
      <description>The number of participants with a R0 resection as defined by a microscopically margin-negative resection, in which no tumor (gross or microscopic) remains in the primary tumor bed.</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">27</enrollment>
    <condition>Pancreatic Cancer</condition>
    <arm_group>
      <arm_group_label>Gemcitabine, Cisplatin and Pembrolizumab</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Gemcitabine</intervention_name>
      <description>Patients will receive treatment on Day 1 and Day 8 of each cycle. Gemcitabine (1000 mg/m2) will be administered IV on Day 1 and Day 8 of each cycle, Q3 weeks with 2 - 4 cycles prior to surgery and then 4-6 cycles after surgery.</description>
      <arm_group_label>Gemcitabine, Cisplatin and Pembrolizumab</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Cisplatin</intervention_name>
      <description>Patients will receive treatment on Day 1 and Day 8 of each cycle. Cisplatin (25 mg/m2) will be administered IV on Day 1 and Day 8 of each cycle, Q3 weeks with 2 - 4 cycles prior to surgery and then 4-6 cycles after surgery.</description>
      <arm_group_label>Gemcitabine, Cisplatin and Pembrolizumab</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Pembrolizumab</intervention_name>
      <description>Patients will receive treatment on Day 1 of each cycle. Pembrolizumab (200 mg) will be administered IV on Day 1 of each cycle, Q3 weeks with 2 - 4 cycles prior to surgery and then 4-6 cycles after surgery. Pembrolizumab (400 mg) will be administered IV Q6 weeks up to 4 cycles as maintenance.</description>
      <arm_group_label>Gemcitabine, Cisplatin and Pembrolizumab</arm_group_label>
      <other_name>KEYTRUDA; anti-PD-1 mAb</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Must have a newly diagnosed, biopsy-proven biliary tract cancer (BTC) including&#xD;
               gallbladder, intrahepatic, extrahepatic, and hilar cholangiocarcinoma.&#xD;
  &#xD;
            -  Resectable BTC (biliary tract cancer)&#xD;
  &#xD;
            -  Measurable disease per RECIST 1.1 as determined by the investigator.&#xD;
  &#xD;
            -  Age ≥18 years.&#xD;
  &#xD;
            -  ECOG (Eastern Cooperative Oncology Group) performance status ≤1 or Karnofsky ≥80&#xD;
  &#xD;
            -  Patients must have adequate organ and marrow function defined by study-specified&#xD;
               laboratory tests.&#xD;
  &#xD;
            -  Patients must have adequate liver function defined by study-specified laboratory&#xD;
               tests.&#xD;
  &#xD;
            -  Patients with chronic or acute HBV or HCV infection must have disease controlled prior&#xD;
               to enrollment.&#xD;
  &#xD;
            -  Women of childbearing potential (WOCBP) must have a negative urine or serum pregnancy&#xD;
               test.&#xD;
  &#xD;
            -  For both Women and Men, must use acceptable form of birth control while on study.&#xD;
  &#xD;
            -  Ability to understand and willingness to sign a written informed consent document.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Receiving, or previously received, any systemic chemotherapy, or investigational agent&#xD;
               for BTC.&#xD;
  &#xD;
            -  Has received prior radiotherapy within 2 weeks of start of study intervention.&#xD;
  &#xD;
            -  Patients with a history of prior treatment with anti-PD-1 and anti-PD-L1.&#xD;
  &#xD;
            -  Have been diagnosed with another cancer or myeloproliferative disorder whose natural&#xD;
               history or treatment has the potential to interfere with safety or efficacy assessment&#xD;
               of this study's investigational drugs.&#xD;
  &#xD;
            -  Has a known history of Human Immunodeficiency Virus (HIV)/AIDS&#xD;
  &#xD;
            -  Has active co-infection with HBV and HDV.&#xD;
  &#xD;
            -  Has a diagnosis of immunodeficiency.&#xD;
  &#xD;
            -  Has active autoimmune disease that has required systemic treatment in the past 2&#xD;
               years.&#xD;
  &#xD;
            -  Systemic or topical corticosteroids at immunosuppressive doses.&#xD;
  &#xD;
            -  Prior allogeneic stem cell transplantation or organ transplantation.&#xD;
  &#xD;
            -  Prior tissue or organ allograft or allogeneic bone marrow transplantation, including&#xD;
               corneal transplants.&#xD;
  &#xD;
            -  Uncontrolled intercurrent active medical and/or psychiatric illness/social&#xD;
               psychosocial problems that that would limit compliance with study requirements.&#xD;
  &#xD;
            -  Uncontrolled intercurrent illness including, but not limited to, uncontrolled&#xD;
               infection, symptomatic congestive heart failure, unstable angina, cardiac arrhythmia,&#xD;
               metastatic cancer, or psychiatric illness/social situations that would limit&#xD;
               compliance with study requirements.&#xD;
  &#xD;
            -  Evidence of clinical ascites.&#xD;
  &#xD;
            -  Has a history of (non-infectious) pneumonitis/interstitial lung disease that required&#xD;
               steroids or has current pneumonitis/interstitial lung disease.&#xD;
  &#xD;
            -  Previously identified allergy or hypersensitivity to monoclonal antibodies or any&#xD;
               component of the study treatment formulations.&#xD;
  &#xD;
            -  Pregnant or breastfeeding.&#xD;
  &#xD;
            -  WOCBP and men with female partners (WOCBP) who are not willing to use contraception.&#xD;
  &#xD;
            -  Subjects unable to undergo venipuncture and/or tolerate venous access.&#xD;
  &#xD;
            -  Patient is at the time of signing informed consent a regular user (including&#xD;
               &quot;recreational use&quot;) of any illicit drugs or had a recent history (within the last&#xD;
               year) of substance abuse (including alcohol).&#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>Marina Baretti, M.D.</last_name>
      <role>Principal Investigator</role>
      <affiliation>SKCCC Johns Hopkins Medical Institution</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Colleen Apostal, RN</last_name>
      <phone>410-614-3644</phone>
      <email>GIClinicalTrials@jhmi.edu</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Joann Santmyer, RN</last_name>
      <phone>410-614-3644</phone>
      <email>GIClinicalTrials@jhmi.edu</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>SKCCC Johns Hopkins</name>
        <address>
          <city>Baltimore</city>
          <state>Maryland</state>
          <zip>21231</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Colleen Apostol, RN</last_name>
        <phone>410-614-3644</phone>
        <email>GIClinicalTrials@jhmi.edu</email>
      </contact>
      <contact_backup>
        <last_name>Joann Santmyer, RN</last_name>
        <phone>410-614-3644</phone>
        <email>GIClinicalTrials@jhmi.edu</email>
      </contact_backup>
      <investigator>
        <last_name>Marina Baretti, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 8, 2023</study_first_submitted>
    <study_first_submitted_qc>August 16, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 21, 2023</study_first_posted>
    <last_update_submitted>August 16, 2023</last_update_submitted>
    <last_update_submitted_qc>August 16, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 21, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Biliary Tract cancer</keyword>
    <keyword>Pembrolizumab</keyword>
    <keyword>Gemcitabine</keyword>
    <keyword>Cisplatin</keyword>
    <keyword>Immunotherapy</keyword>
    <keyword>Potentially resectable biliary tract cancer</keyword>
    <keyword>Anti PD-L1</keyword>
    <keyword>PD-L1</keyword>
    <keyword>Carcinoma</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Biliary Tract Neoplasms</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Gemcitabine</mesh_term>
      <mesh_term>Pembrolizumab</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06001658
  org study id: J2390
  secondary id: IRB00371087
  nct id: NCT06001658
  lead sponsor: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  is us export: No
  The purpose of this study is to determine the safety of peri-operative gemcitabine,
        cisplatin, and pembrolizumab in patients with BTC, as well as whether the combination of
        gemcitabine, cisplatin, and pembrolizumab (gem/cis/pembro) is feasible and lead to pathologic
        responses.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Average minimum Euclidean distance from CD8+ T cells to immunosuppressive tumor-associated macrophages (TAMs) at the per-cell level in patients with a major pathologic response versus pathologic non-responders.
  time frame: 4 years
  description: The evaluable population of this endpoint consist of all patients who receive at least one dose of study drug and have TAMs and CD8 T cell measures at the time of surgery. TAMs being evaluated are the following: immunosuppressive TAMs with high Arginase-1 expression (CD68+CD163+Arg-1hiPDL1-/+), immunosuppressive TAMs with low Arginase-1 expression (CD68+CD163+Arg-1lo PDL1-/+), and less immunosuppressive TAMs (CD68+CD163-HLA-DRhi/CD86hi/PDL1hi)
  measure: Number of participants experiencing grade 3 or above drug-related toxicities
  time frame: 4 years
  description: When calculating the incidence of AEs, each AE (as defined by NCI CTCAE v5.0) will be counted only once for a given subject.
  measure: Number of patients proceeding to surgery without an extended treatment-related delay as a measure of feasibility
  time frame: 144 days
  description: Extended treatment delay is defined as a delay of greater than 60 days of the pre-planned surgical evaluation date, or inability to go to surgery due to an adverse event related to study treatment.
  measure: Major pathologic response rate
  time frame: 8-12 weeks
  description: The number of participants with a major pathologic response as defined by ≤ 10% residual viable tumor cells in the resection of the primary tumor and lymph nodes.
  measure: R0 resection rate
  time frame: 60 days
  description: The number of participants with a R0 resection as defined by a microscopically margin-negative resection, in which no tumor (gross or microscopic) remains in the primary tumor bed.
  arm group label: Gemcitabine, Cisplatin and Pembrolizumab
  arm group type: Experimental
  intervention type: Drug
  intervention name: Gemcitabine
  description: Patients will receive treatment on Day 1 and Day 8 of each cycle. Gemcitabine (1000 mg/m2) will be administered IV on Day 1 and Day 8 of each cycle, Q3 weeks with 2 - 4 cycles prior to surgery and then 4-6 cycles after surgery.
  arm group label: Gemcitabine, Cisplatin and Pembrolizumab
  intervention type: Drug
  intervention name: Cisplatin
  description: Patients will receive treatment on Day 1 and Day 8 of each cycle. Cisplatin (25 mg/m2) will be administered IV on Day 1 and Day 8 of each cycle, Q3 weeks with 2 - 4 cycles prior to surgery and then 4-6 cycles after surgery.
  arm group label: Gemcitabine, Cisplatin and Pembrolizumab
  intervention type: Drug
  intervention name: Pembrolizumab
  description: Patients will receive treatment on Day 1 of each cycle. Pembrolizumab (200 mg) will be administered IV on Day 1 of each cycle, Q3 weeks with 2 - 4 cycles prior to surgery and then 4-6 cycles after surgery. Pembrolizumab (400 mg) will be administered IV Q6 weeks up to 4 cycles as maintenance.
  arm group label: Gemcitabine, Cisplatin and Pembrolizumab
  other name: KEYTRUDA; anti-PD-1 mAb
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Marina Baretti, M.D.
  role: Principal Investigator
  affiliation: SKCCC Johns Hopkins Medical Institution
  last name: Colleen Apostal, RN
  phone: 410-614-3644
  email: GIClinicalTrials@jhmi.edu
  last name: Joann Santmyer, RN
  phone: 410-614-3644
  email: GIClinicalTrials@jhmi.edu
  facility: 
  contact: 
  contact backup: 
  investigator: 
  country: United States
  responsible party type: Sponsor
  mesh term: Biliary Tract Neoplasms
  mesh term: Gemcitabine
  mesh term: Pembrolizumab
  sharing ipd: No