<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/NCT03281382</url>
  </required_header>
  <id_info>
    <org_study_id>11260</org_study_id>
    <nct_id>NCT03281382</nct_id>
  </id_info>
  <brief_title>Phase 1 Trial of Interleukin 12 Gene Therapy for Metastatic Pancreatic Cancer</brief_title>
  <official_title>PHASE 1 TRIAL OF ONCOLYTIC ADENOVIRUS-MEDIATED CYTOTOXIC AND IL-12 GENE THERAPY IN COMBINATION WITH CHEMOTHERAPY FOR THE TREATMENT OF METASTATIC PANCREATIC CANCER</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Henry Ford Health System</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Henry Ford Health System</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase 1 trial will investigate the toxicity of combining interleukin 12 gene therapy&#xD;
      with standard chemotherapy in metastatic pancreatic cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This protocol proposes a phase 1 trial combining oncolytic adenovirus-mediated cytotoxic and&#xD;
      IL-12 gene therapy with chemotherapy in metastatic pancreatic cancer. Nine subjects (3&#xD;
      cohorts, 3 subjects/cohort) with metastatic pancreatic cancer will receive a single&#xD;
      intratumoral injection of the oncolytic Ad5-yCD/mutTKSR39rep-hIL12 adenovirus at one of three&#xD;
      dose levels (cohort 1- 1 x 1011 vp, cohort 2- 3 x 1011 vp, cohort 3- 1 x 1012 vp). Depending&#xD;
      on the location of the target lesion, the adenovirus will be injected either through the&#xD;
      stomach or duodenal wall using endoscopic ultrasound (EUS) guidance. Two days later, subjects&#xD;
      will be administered (orally) 7 days of 5-fluorocytosine (5-FC) prodrug therapy. Fourteen&#xD;
      days after completion of the 5-FC prodrug therapy course, subjects will be administered&#xD;
      chemotherapy at the discretion of the treating physician. On an optional basis, subjects will&#xD;
      be administered [18F]-FHBG, a HSV-1 TK substrate, and will undergo PET imaging to quantify&#xD;
      the intensity, persistence, and biodistribution of HSV-1 TK gene expression in the pancreas.&#xD;
&#xD;
      The primary endpoint is toxicity at day 21. A secondary endpoint is rates of ≥ grade 3 CTCAE&#xD;
      adverse events. Exploratory endpoints include 1) intensity, persistence, and biodistribution&#xD;
      of HSV-1 TK gene expression, and 2) association of immunological measurements (i.e., cytokine&#xD;
      levels, NK cytolytic activity) with toxicity and clinical outcome.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 1, 2017</start_date>
  <completion_date type="Actual">May 28, 2019</completion_date>
  <primary_completion_date type="Actual">May 28, 2019</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>Toxicity of the gene therapy</measure>
    <time_frame>21 days</time_frame>
    <description>grade 1 - 5 CTCAE adverse events</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>&gt;= grade 3 adverse events</measure>
    <time_frame>21 days</time_frame>
    <description>grade 3 - 5 CTCAE adverse events</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PET imaging</measure>
    <time_frame>14 days</time_frame>
    <description>HSV-1 TK gene expression via [18F]-FHBG administration and PET imaging</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Metastatic Pancreatic Cancer</condition>
  <arm_group>
    <arm_group_label>Investigational Arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will receive a single intratumoral injection of the oncolytic Ad5-yCD/mutTKSR39rep-hIL12 adenovirus at one of three dose levels. Two days later, subjects will be administered (orally) 7 days of 5-fluorocytosine (5-FC) prodrug therapy. Fourteen days after completion of the 5-FC prodrug therapy course, subjects will be administered chemotherapy at the discretion of the treating physician. On an optional basis, subjects will be administered [18F]-FHBG, a HSV-1 TK substrate, and will undergo PET imaging to quantify the intensity, persistence, and biodistribution of HSV-1 TK gene expression in the pancreas.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Ad5-yCD/mutTKSR39rep-hIL12</intervention_name>
    <description>Oncolytic adenovirus expressing two suicide genes and human IL-12</description>
    <arm_group_label>Investigational Arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histologically proven (biopsy or cytology) metastatic pancreatic adenocarcinoma.&#xD;
&#xD;
          -  Age ≥ 18 years.&#xD;
&#xD;
          -  No prior treatment (surgery, chemotherapy, radiotherapy, or biological therapy) for&#xD;
             the study cancer.&#xD;
&#xD;
          -  Zubrod performance score of 0 - 2 within 30 days of registration.&#xD;
&#xD;
          -  Subjects must have adequate baseline organ function, as assessed by the following&#xD;
             laboratory values, within 30 days before initiating the study therapy:&#xD;
&#xD;
               -  Adequate renal function with serum creatinine ≤ 1.8 mg/dL or creatinine clearance&#xD;
                  ≥ 50 mL/min/m2.&#xD;
&#xD;
               -  Absolute neutrophil count &gt; 1,000/μL.&#xD;
&#xD;
               -  Hemoglobin &gt; 8.0 g/dL.&#xD;
&#xD;
               -  Platelet count &gt; 100,000/μL.&#xD;
&#xD;
               -  Bilirubin &lt; 2.0 mg/dL.&#xD;
&#xD;
               -  SGOT and SGPT &lt; 3.0 times upper limit of normal (ULN). Subjects with liver&#xD;
                  metastases may have SGOT/SGPT &lt; 5.0 times ULN.&#xD;
&#xD;
          -  Women of childbearing potential and male participants must agree to use a medically&#xD;
             effective means of birth control throughout and for 60 days beyond the treatment phase&#xD;
             of the study.&#xD;
&#xD;
          -  Subjects on oral warfarin anticoagulation therapy may be included in this study, but&#xD;
             must have close monitoring of their coagulation parameters as altered parameters&#xD;
             and/or bleeding have been reported in patients taking Xeloda® and such agents&#xD;
             concomitantly. Subjects on other forms of anti-coagulation therapies may need close&#xD;
             clinical monitoring for signs or symptoms of bleeding.&#xD;
&#xD;
          -  The subject must possess the ability to give informed consent and express a&#xD;
             willingness to meet all of the expected requirements of the protocol for the duration&#xD;
             of the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant and lactating women.&#xD;
&#xD;
          -  Clinical or laboratory evidence of pancreatitis, based on discretion of treating&#xD;
             physician.&#xD;
&#xD;
          -  Serious non-malignant disease (e.g., congestive heart failure or uncontrolled&#xD;
             infections), which, in the opinion of the investigator would compromise study&#xD;
             objectives.&#xD;
&#xD;
          -  Major surgery planned within 3 months of registration other than diagnostic procedures&#xD;
             such as laparoscopy or endoscopic ultrasound and stenting or PEG/PEJ placement.&#xD;
&#xD;
          -  Islet cell tumor, benign cyst, peri-ampullary carcinoma or any non-adenocarcinomas.&#xD;
&#xD;
          -  Acute infection. Acute infection is defined by any viral, bacterial, or fungal&#xD;
             infection that has required specific therapy within 72 hours of initiation of the&#xD;
             study therapy (defined as day 1).&#xD;
&#xD;
          -  Previous history of liver disease including hepatitis.&#xD;
&#xD;
          -  Positive serologic test for Hepatitis B or C at baseline.&#xD;
&#xD;
          -  Immunosuppressive therapy including systemic corticosteroids. Use of inhaled and&#xD;
             topical corticosteroids is permitted.&#xD;
&#xD;
          -  Impaired immunity or susceptibility to serious viral infections.&#xD;
&#xD;
          -  Allergy to any product used on the protocol.&#xD;
&#xD;
          -  Serious medical or psychiatric illness or concomitant medication, which, in the&#xD;
             judgment of the investigator, might interfere with the subject's ability to respond to&#xD;
             or tolerate the treatment or complete the trial.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Henry Ford Hospital</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2022</verification_date>
  <study_first_submitted>September 11, 2017</study_first_submitted>
  <study_first_submitted_qc>September 11, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 13, 2017</study_first_posted>
  <last_update_submitted>February 15, 2022</last_update_submitted>
  <last_update_submitted_qc>February 15, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 2, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Henry Ford Health System</investigator_affiliation>
    <investigator_full_name>David Kwon, MD</investigator_full_name>
    <investigator_title>Medical Director, Center for Cancer Surgery</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>
  <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/NCT03281382
org study id: 11260
nct id: NCT03281382
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This phase 1 trial will investigate the toxicity of combining interleukin 12 gene therapy
      with standard chemotherapy in metastatic pancreatic cancer.
This protocol proposes a phase 1 trial combining oncolytic adenovirus-mediated cytotoxic and
      IL-12 gene therapy with chemotherapy in metastatic pancreatic cancer. Nine subjects (3
      cohorts, 3 subjects/cohort) with metastatic pancreatic cancer will receive a single
      intratumoral injection of the oncolytic Ad5-yCD/mutTKSR39rep-hIL12 adenovirus at one of three
      dose levels (cohort 1- 1 x 1011 vp, cohort 2- 3 x 1011 vp, cohort 3- 1 x 1012 vp). Depending
      on the location of the target lesion, the adenovirus will be injected either through the
      stomach or duodenal wall using endoscopic ultrasound (EUS) guidance. Two days later, subjects
      will be administered (orally) 7 days of 5-fluorocytosine (5-FC) prodrug therapy. Fourteen
      days after completion of the 5-FC prodrug therapy course, subjects will be administered
      chemotherapy at the discretion of the treating physician. On an optional basis, subjects will
      be administered [18F]-FHBG, a HSV-1 TK substrate, and will undergo PET imaging to quantify
      the intensity, persistence, and biodistribution of HSV-1 TK gene expression in the pancreas.

      The primary endpoint is toxicity at day 21. A secondary endpoint is rates of ≥ grade 3 CTCAE
      adverse events. Exploratory endpoints include 1) intensity, persistence, and biodistribution
      of HSV-1 TK gene expression, and 2) association of immunological measurements (i.e., cytokine
      levels, NK cytolytic activity) with toxicity and clinical outcome.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Toxicity of the gene therapy
time frame: 21 days
description: grade 1 - 5 CTCAE adverse events
measure: >= grade 3 adverse events
time frame: 21 days
description: grade 3 - 5 CTCAE adverse events
measure: PET imaging
time frame: 14 days
description: HSV-1 TK gene expression via [18F]-FHBG administration and PET imaging
arm group label: Investigational Arm
arm group type: Experimental
description: Patients will receive a single intratumoral injection of the oncolytic Ad5-yCD/mutTKSR39rep-hIL12 adenovirus at one of three dose levels. Two days later, subjects will be administered (orally) 7 days of 5-fluorocytosine (5-FC) prodrug therapy. Fourteen days after completion of the 5-FC prodrug therapy course, subjects will be administered chemotherapy at the discretion of the treating physician. On an optional basis, subjects will be administered [18F]-FHBG, a HSV-1 TK substrate, and will undergo PET imaging to quantify the intensity, persistence, and biodistribution of HSV-1 TK gene expression in the pancreas.
intervention type: Biological
intervention name: Ad5-yCD/mutTKSR39rep-hIL12
description: Oncolytic adenovirus expressing two suicide genes and human IL-12
arm group label: Investigational Arm
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Henry Ford Health System
investigator full name: David Kwon, MD
investigator title: Medical Director, Center for Cancer Surgery
mesh term: Pancreatic Neoplasms
sharing ipd: No