<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/NCT03006302</url>
  </required_header>
  <id_info>
    <org_study_id>J16173</org_study_id>
    <secondary_id>IRB00118520</secondary_id>
    <secondary_id>5P01CA247886-02</secondary_id>
    <nct_id>NCT03006302</nct_id>
  </id_info>
  <brief_title>Epacadostat, Pembrolizumab, and CRS-207, With or Without CY/GVAX Pancreas in Patients With Metastatic Pancreas Cancer</brief_title>
  <official_title>Phase 2 Study of Epacadostat, Pembrolizumab, and CRS-207, With or Without Cyclophosphamide and GVAX Pancreas Vaccine in Patients With Metastatic Pancreas Cancer</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>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will enroll patients who have metastatic pancreatic cancer and have progressed on&#xD;
      prior chemotherapy.&#xD;
&#xD;
      Part 1 (dose escalation) participants will receive&#xD;
      epacadostat/pembrolizumab/cyclophosphamide(CY)/GVAX pancreas vaccine followed by&#xD;
      epacadostat/pembrolizumab/CRS-207, Part 1X (dose escalation) participants will receive&#xD;
      epacadostat/pembrolizumab/CRS-207. Part 2X (dose expansion) participants will receive&#xD;
      epacadostat/pembrolizumab/CRS-207.&#xD;
&#xD;
      The primary objectives of this study are to determine the recommended dose of epacadostat in&#xD;
      this combination and assess survival of subjects in both treatment groups.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">January 31, 2018</start_date>
  <completion_date type="Anticipated">December 1, 2023</completion_date>
  <primary_completion_date type="Actual">August 22, 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>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Recommended Dose of Epacadostat</measure>
    <time_frame>1 year</time_frame>
    <description>Evaluate 4 dose levels of epacadostat, in order to determine recommended dose for use in combination with pembrolizumab, CY, GVAX, and CRS-207</description>
  </primary_outcome>
  <primary_outcome>
    <measure>6 Month Survival</measure>
    <time_frame>4 years</time_frame>
    <description>Proportion of subjects who are alive 6 months or longer after the date of randomization</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of participants experiencing drug-related adverse events (AEs) requiring treatment discontinuation</measure>
    <time_frame>4 years</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">40</enrollment>
  <condition>Metastatic Pancreatic Adenocarcinoma</condition>
  <arm_group>
    <arm_group_label>Epacadostat/Pembrolizumab/CY/GVAX/CRS-207</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Epacadostat/Pembrolizumab/CRS-207</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Epacadostat</intervention_name>
    <description>50, 100, 300, or 600 mg taken by mouth twice a day, every day of each cycle</description>
    <arm_group_label>Epacadostat/Pembrolizumab/CRS-207</arm_group_label>
    <arm_group_label>Epacadostat/Pembrolizumab/CY/GVAX/CRS-207</arm_group_label>
    <other_name>INCB024360</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pembrolizumab</intervention_name>
    <description>200 mg IV on Day 1 of each cycle</description>
    <arm_group_label>Epacadostat/Pembrolizumab/CRS-207</arm_group_label>
    <arm_group_label>Epacadostat/Pembrolizumab/CY/GVAX/CRS-207</arm_group_label>
    <other_name>MK-3475</other_name>
    <other_name>anti-PD-1 mAb</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>CRS-207</intervention_name>
    <description>1x10^9 CFU given IV on Day 2 of Cycles 3-6 (Arm A) or Day 2 of Cycles 1-6 (Arm B)</description>
    <arm_group_label>Epacadostat/Pembrolizumab/CRS-207</arm_group_label>
    <arm_group_label>Epacadostat/Pembrolizumab/CY/GVAX/CRS-207</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>CY</intervention_name>
    <description>200 mg/m^2 given IV on Day 1 of Cycles 1-2 (Arm A only)</description>
    <arm_group_label>Epacadostat/Pembrolizumab/CY/GVAX/CRS-207</arm_group_label>
    <other_name>cyclophosphamide</other_name>
    <other_name>cytoxan</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>GVAX</intervention_name>
    <description>5x10^8 cells given as 6 intradermal injections on Day 2 of Cycles 1-2 (Arm A only)</description>
    <arm_group_label>Epacadostat/Pembrolizumab/CY/GVAX/CRS-207</arm_group_label>
    <other_name>GVAX Pancreas Vaccine</other_name>
    <other_name>Panc 10.05 pcDNA-1/GM-Neo, Panc 6.03 pcDNA-1/GM-Neo</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria (abbreviated):&#xD;
&#xD;
          -  Documented adenocarcinoma of the pancreas&#xD;
&#xD;
          -  Have disease progression after prior chemotherapy for metastatic pancreas cancer (or&#xD;
             adjuvant or neoadjuvant if progression occurred within 6 months of completing this&#xD;
             regimen)&#xD;
&#xD;
          -  Presence of at least one measurable lesion&#xD;
&#xD;
          -  Patient acceptance to have a tumor biopsy of an accessible lesion at 2 time points&#xD;
             (baseline and on study)&#xD;
&#xD;
          -  ECOG performance status of 0 or 1&#xD;
&#xD;
          -  Life expectancy of greater than 3 months&#xD;
&#xD;
          -  Adequate organ and marrow function defined by study-specified laboratory tests&#xD;
&#xD;
        Exclusion Criteria (abbreviated):&#xD;
&#xD;
          -  Brain metastases&#xD;
&#xD;
          -  Clinical or radiographic ascites (some trace amount may be allowed)&#xD;
&#xD;
          -  Rapidly progressing disease&#xD;
&#xD;
          -  Live vaccine within 30 days of study treatment (flu vaccine allowed)&#xD;
&#xD;
          -  Surgery within 28 days of study treatment (some exceptions for minor procedures)&#xD;
&#xD;
          -  Use of an investigational agent or device within 28 days of study treatment.&#xD;
&#xD;
          -  Chemotherapy, radiation, or biological cancer therapy within 14 days of study&#xD;
             treatment.&#xD;
&#xD;
          -  Prior treatment with anti-CTLA-4, anti-PD-1, anti-PD-L1, or anti PD-L2, or with IDO&#xD;
             inhibitor.&#xD;
&#xD;
          -  Use of growth factors within 14 days of study treatment&#xD;
&#xD;
          -  Use of any systemic steroids within 14 days of study treatment or other&#xD;
             immunosuppressive agents within 7 days of study treatment.&#xD;
&#xD;
          -  Use of more than 2 g/day of acetaminophen&#xD;
&#xD;
          -  Use of any UGT1A9 inhibitor&#xD;
&#xD;
          -  Use of warfarin&#xD;
&#xD;
          -  Use of MAOIs or drugs with significant MAOI activity within the 21 days of screening&#xD;
&#xD;
          -  History of Seratonin Syndome&#xD;
&#xD;
          -  Known allergy to both penicillin and sulfa&#xD;
&#xD;
          -  Known or suspected hypersensitivity to any monoclonal antibody or any study drug&#xD;
             component&#xD;
&#xD;
          -  Have artificial joints or implants that cannot be easily removed or a history of&#xD;
             infection associated with an implant&#xD;
&#xD;
          -  Significant or malignant pleural effusion&#xD;
&#xD;
          -  New pulmonary embolism, extremity deep venous thromboembolism, or portal vein&#xD;
             thrombosis within 2 months of study enrollment&#xD;
&#xD;
          -  History of autoimmune disease (exceptions for Graves or Hashimoto's disease, vitiligo,&#xD;
             and type I diabetes mellitus)&#xD;
&#xD;
          -  Gastrointestinal condition that may affect drug absorption&#xD;
&#xD;
          -  Significant heart disease or heart disease requiring antibiotic for prevention of&#xD;
             endocarditis&#xD;
&#xD;
          -  History of abnormal electrocardiogram (ECG) that is deemed meaningful by the&#xD;
             investigator&#xD;
&#xD;
          -  History of (non-infectious) pneumonitis that required steroids, evidence of&#xD;
             interstitial lung disease or active, non-infectious pneumonitis&#xD;
&#xD;
          -  Pulse oximetry of &lt; 92% on room air or the need for supplemental home oxygen&#xD;
&#xD;
          -  Infection with HIV, hepatitis B or hepatitis C&#xD;
&#xD;
          -  Other conditions, including alcohol or drug dependence, intercurrent illness, or lack&#xD;
             of sufficient peripheral venous access that would affect the patient's ability to&#xD;
             comply with study visits and procedures&#xD;
&#xD;
          -  Pregnant or breastfeeding women&#xD;
&#xD;
          -  Unwillingness or inability to follow the study schedule for any reason&#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>Dung Le, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21287</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>December 28, 2016</study_first_submitted>
  <study_first_submitted_qc>December 28, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 30, 2016</study_first_posted>
  <last_update_submitted>September 5, 2023</last_update_submitted>
  <last_update_submitted_qc>September 5, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 8, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>pancreatic cancer</keyword>
  <keyword>vaccine</keyword>
  <keyword>immunotherapy</keyword>
  <keyword>MK-3475</keyword>
  <keyword>PD-1</keyword>
  <keyword>IDO</keyword>
  <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>Cyclophosphamide</mesh_term>
    <mesh_term>Pembrolizumab</mesh_term>
  </intervention_browse>
  <!-- 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/NCT03006302
org study id: J16173
secondary id: IRB00118520
secondary id: 5P01CA247886-02
nct id: NCT03006302
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This study will enroll patients who have metastatic pancreatic cancer and have progressed on
      prior chemotherapy.

      Part 1 (dose escalation) participants will receive
      epacadostat/pembrolizumab/cyclophosphamide(CY)/GVAX pancreas vaccine followed by
      epacadostat/pembrolizumab/CRS-207, Part 1X (dose escalation) participants will receive
      epacadostat/pembrolizumab/CRS-207. Part 2X (dose expansion) participants will receive
      epacadostat/pembrolizumab/CRS-207.

      The primary objectives of this study are to determine the recommended dose of epacadostat in
      this combination and assess survival of subjects in both treatment groups.
allocation: Non-Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Recommended Dose of Epacadostat
time frame: 1 year
description: Evaluate 4 dose levels of epacadostat, in order to determine recommended dose for use in combination with pembrolizumab, CY, GVAX, and CRS-207
measure: 6 Month Survival
time frame: 4 years
description: Proportion of subjects who are alive 6 months or longer after the date of randomization
measure: Number of participants experiencing drug-related adverse events (AEs) requiring treatment discontinuation
time frame: 4 years
arm group label: Epacadostat/Pembrolizumab/CY/GVAX/CRS-207
arm group type: Experimental
arm group label: Epacadostat/Pembrolizumab/CRS-207
arm group type: Experimental
intervention type: Drug
intervention name: Epacadostat
description: 50, 100, 300, or 600 mg taken by mouth twice a day, every day of each cycle
arm group label: Epacadostat/Pembrolizumab/CRS-207
arm group label: Epacadostat/Pembrolizumab/CY/GVAX/CRS-207
other name: INCB024360
intervention type: Drug
intervention name: Pembrolizumab
description: 200 mg IV on Day 1 of each cycle
arm group label: Epacadostat/Pembrolizumab/CRS-207
arm group label: Epacadostat/Pembrolizumab/CY/GVAX/CRS-207
other name: MK-3475
other name: anti-PD-1 mAb
intervention type: Biological
intervention name: CRS-207
description: 1x10^9 CFU given IV on Day 2 of Cycles 3-6 (Arm A) or Day 2 of Cycles 1-6 (Arm B)
arm group label: Epacadostat/Pembrolizumab/CRS-207
arm group label: Epacadostat/Pembrolizumab/CY/GVAX/CRS-207
intervention type: Drug
intervention name: CY
description: 200 mg/m^2 given IV on Day 1 of Cycles 1-2 (Arm A only)
arm group label: Epacadostat/Pembrolizumab/CY/GVAX/CRS-207
other name: cyclophosphamide
other name: cytoxan
intervention type: Biological
intervention name: GVAX
description: 5x10^8 cells given as 6 intradermal injections on Day 2 of Cycles 1-2 (Arm A only)
arm group label: Epacadostat/Pembrolizumab/CY/GVAX/CRS-207
other name: GVAX Pancreas Vaccine
other name: Panc 10.05 pcDNA-1/GM-Neo, Panc 6.03 pcDNA-1/GM-Neo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Dung Le, M.D.
role: Principal Investigator
affiliation: The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
facility: 
country: United States
responsible party type: Sponsor
mesh term: Pancreatic Neoplasms
mesh term: Cyclophosphamide
mesh term: Pembrolizumab