<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/NCT03001518</url>
  </required_header>
  <id_info>
    <org_study_id>Pro00077435</org_study_id>
    <nct_id>NCT03001518</nct_id>
  </id_info>
  <brief_title>Immunologic Signatures Following Surgery for Pancreatic Cancer</brief_title>
  <official_title>Immunologic Signatures Following Surgery for Pancreatic Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Duke University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Duke 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>
      The goal of this pilot study is to evaluate and describe the immunologic and overall outcomes&#xD;
      of subjects who undergo routine pancreatectomy with or without irreversible electroporation&#xD;
      (IRE) for pancreatic cancer. Immunologic markers in the blood will be measured at several&#xD;
      time points before and after surgery to determine if surgical approach is associated with&#xD;
      different immunologic responses. Secondary outcomes will include mortality and morbidity;&#xD;
      operative time; blood loss and transfusion requirements; and oncologic outcomes such as:&#xD;
      margin status, lymph node harvest, disease-free survival, and overall survival. Analysis of&#xD;
      immune response will help the investigator determine whether to expand the pilot into a&#xD;
      larger study.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Subjects will have blood draws at the following timepoints: Pre-op, 1-2 days post-op, 3-5&#xD;
      days post-op, and 1-4 months post-op. At each timepoint, three 8.5mL ACD (yellow top)&#xD;
      vacutainer tubes will be drawn by the Biobank and Translational Research Core (BRTC), study&#xD;
      personnel, or hospital phlebotomists. The blood will be processed for PBMC isolation by BRTC&#xD;
      for Dr. Weinhold's laboratory and will be viable within 8 hours of draw. These timepoints for&#xD;
      blood draws are at the same time as usual operative care and will not require additional&#xD;
      visits on the part of the subject.&#xD;
&#xD;
      For this study we will extensively utilize several polychromatic flow cytometry (PFC)&#xD;
      platforms to follow activation, maturation, exhaustion, and proliferation patterns within&#xD;
      CD4+ and CD8+ subsets of T-cells. We will also utilize an intracellular cytokine staining&#xD;
      (ICS) platform in efforts to detect anti-tumor associated antigen (TAA) responses by CD4+ and&#xD;
      CD8+ T cells from peripheral blood mononuclear cells (PBMC) as well as lymphocytes&#xD;
      infiltrating the patient's tumor. These assays are designed to measure antigen-driven&#xD;
      intracellular production of IFN-γ, TNF-α, and IL-2, as well as the degranulation marker&#xD;
      CD107. This strategy enables us to not only document individual cytokine responses, but to&#xD;
      also assess (through Boolean gating) changes in relative polyfunctionality of the responses.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 4, 2017</start_date>
  <completion_date type="Actual">January 6, 2023</completion_date>
  <primary_completion_date type="Actual">January 7, 2021</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>immune response</measure>
    <time_frame>preoperatively to 3 months postoperatively</time_frame>
    <description>proliferation of immune cells in peripheral plasma</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>90-day mortality</measure>
    <time_frame>90 days</time_frame>
    <description>death by 90 days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>surgical-site infection (SSI)</measure>
    <time_frame>90 days</time_frame>
    <description>occurrence of superficial or deep infection of incision(s), by erythema/warmth/pain/swelling, need for antibiotics, positive wound cultures, purulent drainage/abscess, need to open skin incision, fascial dehiscence, etc. or documentation in the record of SSI. Organ/space infection indicated by abscess, anastomotic dehiscence, positive culture, etc. or documentation in the record of same.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>pancreatic leak by qualitative appearance or amylase level</measure>
    <time_frame>90 days</time_frame>
    <description>Drain output or CT-guided drainage consistent with pancreatic fluid in appearance and/or amylase level, or documentation in record of same.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>operative time</measure>
    <time_frame>1 day</time_frame>
    <description>time from start to end of operation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>use of neoadjuvant therapy</measure>
    <time_frame>1 day</time_frame>
    <description>used = 1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>use of adjuvant therapy</measure>
    <time_frame>90 days</time_frame>
    <description>used = 1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CA 19-9 level</measure>
    <time_frame>90 days</time_frame>
    <description>result</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>return to operating room</measure>
    <time_frame>90 days</time_frame>
    <description>Reoperation for exploration or repair of complication of primary procedure. Does not include wound debridement, placement of inferior vena cava filter, interventional radiology procedures, or other procedures unrelated to the initial procedure.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Non-SSI infection</measure>
    <time_frame>90 days</time_frame>
    <description>Any infection not covered by surgical-site infection, such as urinary tract infection or pneumonia.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>margin status</measure>
    <time_frame>1 week</time_frame>
    <description>clean or unclean</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>intraoperative transfusion</measure>
    <time_frame>1 day</time_frame>
    <description>used = 1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>lymph node status</measure>
    <time_frame>1 week</time_frame>
    <description>positive or negative</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>overall survival</measure>
    <time_frame>5 years</time_frame>
    <description>number of months alive</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>disease-free survival</measure>
    <time_frame>5 years</time_frame>
    <description>number of months without disease</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">33</enrollment>
  <condition>Pancreatic Cancer</condition>
  <condition>Surgery</condition>
  <arm_group>
    <arm_group_label>Surgery</arm_group_label>
    <description>No intervention. Patients who undergo surgical resection of their pancreatic cancer.</description>
  </arm_group>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Plasma from 4 blood draws&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patients with pancreatic ductal adenocarcinoma who undergo surgical resection of the&#xD;
        cancer, with or without irreversible electroporation.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subject must be at least 18 years of age and at least the minimum age of majority&#xD;
             according to applicable State or Country Law.&#xD;
&#xD;
          -  Subject is a suitable surgical candidate, i.e., is able to undergo general anesthesia&#xD;
             and pancreatectomy for diagnosis of cancer&#xD;
&#xD;
          -  Subject is willing and able to undergo additional blood draws&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        • Subject is not a suitable candidate for surgery, or surgery is unable to be completed&#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>Sabino Zani, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Duke Health</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Duke University Health System</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>December 15, 2016</study_first_submitted>
  <study_first_submitted_qc>December 20, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 23, 2016</study_first_posted>
  <last_update_submitted>June 27, 2023</last_update_submitted>
  <last_update_submitted_qc>June 27, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 28, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pancreatic Neoplasms</mesh_term>
  </condition_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/NCT03001518
org study id: Pro00077435
nct id: NCT03001518
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The goal of this pilot study is to evaluate and describe the immunologic and overall outcomes
      of subjects who undergo routine pancreatectomy with or without irreversible electroporation
      (IRE) for pancreatic cancer. Immunologic markers in the blood will be measured at several
      time points before and after surgery to determine if surgical approach is associated with
      different immunologic responses. Secondary outcomes will include mortality and morbidity;
      operative time; blood loss and transfusion requirements; and oncologic outcomes such as:
      margin status, lymph node harvest, disease-free survival, and overall survival. Analysis of
      immune response will help the investigator determine whether to expand the pilot into a
      larger study.
Subjects will have blood draws at the following timepoints: Pre-op, 1-2 days post-op, 3-5
      days post-op, and 1-4 months post-op. At each timepoint, three 8.5mL ACD (yellow top)
      vacutainer tubes will be drawn by the Biobank and Translational Research Core (BRTC), study
      personnel, or hospital phlebotomists. The blood will be processed for PBMC isolation by BRTC
      for Dr. Weinhold's laboratory and will be viable within 8 hours of draw. These timepoints for
      blood draws are at the same time as usual operative care and will not require additional
      visits on the part of the subject.

      For this study we will extensively utilize several polychromatic flow cytometry (PFC)
      platforms to follow activation, maturation, exhaustion, and proliferation patterns within
      CD4+ and CD8+ subsets of T-cells. We will also utilize an intracellular cytokine staining
      (ICS) platform in efforts to detect anti-tumor associated antigen (TAA) responses by CD4+ and
      CD8+ T cells from peripheral blood mononuclear cells (PBMC) as well as lymphocytes
      infiltrating the patient's tumor. These assays are designed to measure antigen-driven
      intracellular production of IFN-γ, TNF-α, and IL-2, as well as the degranulation marker
      CD107. This strategy enables us to not only document individual cytokine responses, but to
      also assess (through Boolean gating) changes in relative polyfunctionality of the responses.
observational model: Cohort
time perspective: Prospective
measure: immune response
time frame: preoperatively to 3 months postoperatively
description: proliferation of immune cells in peripheral plasma
measure: 90-day mortality
time frame: 90 days
description: death by 90 days
measure: surgical-site infection (SSI)
time frame: 90 days
description: occurrence of superficial or deep infection of incision(s), by erythema/warmth/pain/swelling, need for antibiotics, positive wound cultures, purulent drainage/abscess, need to open skin incision, fascial dehiscence, etc. or documentation in the record of SSI. Organ/space infection indicated by abscess, anastomotic dehiscence, positive culture, etc. or documentation in the record of same.
measure: pancreatic leak by qualitative appearance or amylase level
time frame: 90 days
description: Drain output or CT-guided drainage consistent with pancreatic fluid in appearance and/or amylase level, or documentation in record of same.
measure: operative time
time frame: 1 day
description: time from start to end of operation
measure: use of neoadjuvant therapy
time frame: 1 day
description: used = 1
measure: use of adjuvant therapy
time frame: 90 days
description: used = 1
measure: CA 19-9 level
time frame: 90 days
description: result
measure: return to operating room
time frame: 90 days
description: Reoperation for exploration or repair of complication of primary procedure. Does not include wound debridement, placement of inferior vena cava filter, interventional radiology procedures, or other procedures unrelated to the initial procedure.
measure: Non-SSI infection
time frame: 90 days
description: Any infection not covered by surgical-site infection, such as urinary tract infection or pneumonia.
measure: margin status
time frame: 1 week
description: clean or unclean
measure: intraoperative transfusion
time frame: 1 day
description: used = 1
measure: lymph node status
time frame: 1 week
description: positive or negative
measure: overall survival
time frame: 5 years
description: number of months alive
measure: disease-free survival
time frame: 5 years
description: number of months without disease
arm group label: Surgery
description: No intervention. Patients who undergo surgical resection of their pancreatic cancer.
Plasma from 4 blood draws
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Sabino Zani, MD
role: Principal Investigator
affiliation: Duke Health
facility: 
country: United States
responsible party type: Sponsor
mesh term: Pancreatic Neoplasms
sharing ipd: No