<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/NCT03245489</url>
  </required_header>
  <id_info>
    <org_study_id>102727</org_study_id>
    <nct_id>NCT03245489</nct_id>
  </id_info>
  <brief_title>Pembrolizumab in Combination With Anti-platelet Therapy for Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck</brief_title>
  <official_title>Pembrolizumab in Combination With Anti-platelet Therapy for Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Medical University of South Carolina</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Medical University of South Carolina</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 see if anti-platelet therapy combined with anti-PD-1&#xD;
      immunotherapy can cause a more favorable immunologic response thatn with immunotherapy alone&#xD;
      in patients with recurrent or metastatic squamous cell carcinoma of the head and neck.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">October 20, 2017</start_date>
  <completion_date type="Anticipated">March 31, 2024</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2023</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Effect of Pembro + antiplatelet on major cellular parameters</measure>
    <time_frame>12 weeks</time_frame>
    <description>Immunologic response profile will be measured by changes in major cellular parameters in peripheral blood mononuclear cells pheotyped by flow cytometry for MDSCs, T and B cell activation markers and polyclonal IFNy-production by CD4 and CD8 response after P/I stimulation) in pembrolizumab alone and pembrolizumab + antiplatelet therapy. Markers will be measured at baseline, end of the first regimen and end of the second regimen. Changes in cellular parameters from the previous timepoint will be evaluated using a repeated measures ANOVA model. Cellular parameters will be evaluated in aggregate to report the immunologic response.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Effect of Pembro + antiplatelets on immunologic markers</measure>
    <time_frame>12 weeks</time_frame>
    <description>Immunologic markers will be measured in patients who have been treated with two cycles of pembrolizumab alone and who are pembrolizumab naive. Markers will be evaluated by looking at phyenotyping by flow cytometry and changes of 65-panel systemic cytokines and chemokine levels. Markers will be measured at baseline, end of the first regimen and end of the second regimen. Changes to markers will be reported in aggregate to show the overall immunologic effect of the combination of pembrolizumab + Anti-platelets in patients.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frequency of adverse events reported</measure>
    <time_frame>12 weeks</time_frame>
    <description>Safety data will be tabulated by type and grade of adverse event and will use CTCAE v. 4.0</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tumor response rate</measure>
    <time_frame>12 weeks</time_frame>
    <description>Objective response will be evaluated with computed tomography (CT) of the neck, chest and abdomen at baseline and post-treatment using RECIST 1.1 criteria.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Head and Neck Cancer</condition>
  <arm_group>
    <arm_group_label>Group 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Group 1 will be treated with Regimen A, followed by Regimen B. Regimen A is pembrolizumab, ASA and clopidogrel daily for 6 weeks. Regimen B is pembrolizumab alone for 6 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Group 2 will be treated with Regimen B, followed by Regimen A. Regimen B is pembrolizumab alone for 6 weeks. Regimen A is pembrolizumab, ASA and clopidogrel daily for 6 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pembrolizumab</intervention_name>
    <description>200mg intravenous (IV) over 30 minutes</description>
    <arm_group_label>Group 1</arm_group_label>
    <arm_group_label>Group 2</arm_group_label>
    <other_name>Keytruda</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Clopidogrel</intervention_name>
    <description>75mg/day oral</description>
    <arm_group_label>Group 1</arm_group_label>
    <arm_group_label>Group 2</arm_group_label>
    <other_name>Plavix</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>acetylsalicylic acid</intervention_name>
    <description>81mg/day oral</description>
    <arm_group_label>Group 1</arm_group_label>
    <arm_group_label>Group 2</arm_group_label>
    <other_name>ASA</other_name>
    <other_name>aspirin</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Subject has pathologic confirmation of recurrent or metastatic HNSCC, regardless of&#xD;
             HPV status.&#xD;
&#xD;
          2. Subject has tumor that expresses PD-L1 (Combined Positive Score [CPS] &gt; 1) as&#xD;
             determined by an FDA-approved test or subject has experienced disease progression on&#xD;
             or after platinum-containing chemotherapy.&#xD;
&#xD;
          3. Subject's scans have been reviewed at head and neck tumor board to assess tumor&#xD;
             involvement.&#xD;
&#xD;
          4. Subject is 18 years of age or older.&#xD;
&#xD;
          5. Subject has measurable disease according to RECIST 1.1. Tumor lesions situated in&#xD;
             previously irradiated areas are considered measurable if progression has been&#xD;
             demonstrated in such lesions.&#xD;
&#xD;
          6. Subject has an ECOG performance status of 0 to 2&#xD;
&#xD;
          7. Subject has estimated life expectancy of at least 3 months.&#xD;
&#xD;
          8. Subject has adequate hematologic function, defined as:&#xD;
&#xD;
               1. ANC &gt;1000 K/CUMM&#xD;
&#xD;
               2. Hemoglobin &gt;8.0 Grams/dL&#xD;
&#xD;
               3. Platelets &gt;75,000 K/CUMM&#xD;
&#xD;
               4. INR &lt; 1.7&#xD;
&#xD;
          9. Subject has adequate renal function, defined as estimated creatinine clearance &gt; 30&#xD;
             mL/min according to the Cockcroft-Gault formula.&#xD;
&#xD;
         10. Subject has adequate hepatic function, defined as:&#xD;
&#xD;
               1. Total bilirubin ≤ 1.5 x ULN&#xD;
&#xD;
               2. AST and ALT ≤ 2.5 x ULN&#xD;
&#xD;
         11. Female and male subjects of childbearing potential must be willing to use an adequate&#xD;
             method of contraception for the course of the study through 120 days after the last&#xD;
             dose of study medication. Effective forms of contraception include abstinence,&#xD;
             hormonal contraceptive in conjunction with a barrier method, or a double barrier&#xD;
             method. Women of non-child-bearing potential may be included if they are either&#xD;
             surgically sterile or have been post-menopausal for &gt; 1 year.&#xD;
&#xD;
        Note: Female subjects of childbearing potential must have a negative urine or serum&#xD;
        pregnancy test within 14 days of registration. If the urine test is positive or cannot be&#xD;
        confirmed as negative, a serum pregnancy test will be required.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Subject is receiving concomitant immunosuppressive therapy, defined as:&#xD;
&#xD;
               1. Immunosuppressants, including: tacrolimus, sirolimus, everolimus, cyclosporine,&#xD;
                  azathioprine, mycophenolate mofetil, antithymocyte globulin, basiliximab,&#xD;
                  belatacept&#xD;
&#xD;
               2. Systemic corticosteroids (except for short term treatment of allergic reactions&#xD;
                  or for treatment of irAE). Steroids with no or minimal systemic effect (topical,&#xD;
                  inhalation) are allowed.&#xD;
&#xD;
               3. Chemotherapy&#xD;
&#xD;
               4. Immunotherapy&#xD;
&#xD;
               5. Monoclonal antibodies&#xD;
&#xD;
          2. Concurrent anticancer treatment within 14 days before the start of trial treatment.&#xD;
&#xD;
          3. Subject has had major surgery within the last 28 days.&#xD;
&#xD;
          4. Subject has an underlying bleeding disorder.&#xD;
&#xD;
          5. Subjects requiring re-irradiation to head and neck.&#xD;
&#xD;
          6. Subject is receiving anticoagulation (see section 7.2 for medication examples).&#xD;
             Subjects must have a washout period of 7 days from registration.&#xD;
&#xD;
          7. Subject has HNSCC with abutment or encasement of the internal carotid artery, external&#xD;
             carotid artery or common carotid artery or any of the arterial branches.&#xD;
&#xD;
          8. Subject has a draining fistula or wound in the head/neck.&#xD;
&#xD;
          9. Subject with known aneurysm or pseudoaneurysm of the head/neck related to surgery.&#xD;
&#xD;
         10. Subject has uncontrolled CNS metastases. Subjects with previously treated brain&#xD;
             metastases will be allowed if the brain metastases have been stable without&#xD;
             CNS-directed therapy (such as radiation or surgery) or steroid treatment for for at&#xD;
             least 4 weeks prior to registration.&#xD;
&#xD;
         11. Receipt of any organ transplantation.&#xD;
&#xD;
         12. Active or history of any autoimmune disease (except type I DM, vitiligo, psoriasis,&#xD;
             hypo- or hyperthyroid disease not requiring immunosuppressive treatment, which are&#xD;
             allowed) or immunodeficiencies.&#xD;
&#xD;
         13. Known severe hypersensitivity reactions to monoclonal antibodies (grade ≥ 3NCI-CTCAE&#xD;
             v4.0), any history of anaphylaxis or uncontrolled asthma.&#xD;
&#xD;
         14. Subjects who have a hypersensitivity to aspirin or NSAIDs.&#xD;
&#xD;
         15. Concurrent NSAID therapy (see section 7 for examples). Subjects must have a washout&#xD;
             period of 7 days from registration.&#xD;
&#xD;
         16. Subjects with an acute gastrointestinal ulcer.&#xD;
&#xD;
         17. Subjects with active hemorrhagic diathesis.&#xD;
&#xD;
         18. Clinically significant (i.e., active) cardiovascular disease: cerebral vascular&#xD;
             accident/stroke (&lt; 6 months prior to enrollment), myocardial infarction (&lt; 6 months&#xD;
             prior to enrollment), unstable angina, congestive heart failure (NYHA class ≥ II), or&#xD;
             serious uncontrolled cardiac arrhythmia.&#xD;
&#xD;
         19. All other significant diseases, which in the opinion of the investigator, may impair&#xD;
             the subject's tolerance of trial treatment.&#xD;
&#xD;
         20. Vaccination within 4 weeks of the 1st dose of pembrolizumab and while on study is&#xD;
             prohibited EXCEPT for administration of inactivated vaccines (e.g. inactivated&#xD;
             influenza vaccine).&#xD;
&#xD;
         21. Women who are pregnant or nursing.&#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>John Kaczmar, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Medical University of South Carolina</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Christina Godwin</last_name>
    <phone>843-792-8876</phone>
    <email>hcc-clinical-trials@musc.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>Medical University of South Carolina</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29425</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Christina Godwin</last_name>
      <phone>843-792-8876</phone>
      <email>hcc-clinical-trials@musc.edu</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>June 13, 2017</study_first_submitted>
  <study_first_submitted_qc>August 9, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 10, 2017</study_first_posted>
  <last_update_submitted>August 10, 2023</last_update_submitted>
  <last_update_submitted_qc>August 10, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 14, 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>Carcinoma, Squamous Cell</mesh_term>
    <mesh_term>Squamous Cell Carcinoma of Head and Neck</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Aspirin</mesh_term>
    <mesh_term>Pembrolizumab</mesh_term>
    <mesh_term>Clopidogrel</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/NCT03245489
org study id: 102727
nct id: NCT03245489
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
The purpose of this study is to see if anti-platelet therapy combined with anti-PD-1
      immunotherapy can cause a more favorable immunologic response thatn with immunotherapy alone
      in patients with recurrent or metastatic squamous cell carcinoma of the head and neck.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Effect of Pembro + antiplatelet on major cellular parameters
time frame: 12 weeks
description: Immunologic response profile will be measured by changes in major cellular parameters in peripheral blood mononuclear cells pheotyped by flow cytometry for MDSCs, T and B cell activation markers and polyclonal IFNy-production by CD4 and CD8 response after P/I stimulation) in pembrolizumab alone and pembrolizumab + antiplatelet therapy. Markers will be measured at baseline, end of the first regimen and end of the second regimen. Changes in cellular parameters from the previous timepoint will be evaluated using a repeated measures ANOVA model. Cellular parameters will be evaluated in aggregate to report the immunologic response.
measure: Effect of Pembro + antiplatelets on immunologic markers
time frame: 12 weeks
description: Immunologic markers will be measured in patients who have been treated with two cycles of pembrolizumab alone and who are pembrolizumab naive. Markers will be evaluated by looking at phyenotyping by flow cytometry and changes of 65-panel systemic cytokines and chemokine levels. Markers will be measured at baseline, end of the first regimen and end of the second regimen. Changes to markers will be reported in aggregate to show the overall immunologic effect of the combination of pembrolizumab + Anti-platelets in patients.
measure: Frequency of adverse events reported
time frame: 12 weeks
description: Safety data will be tabulated by type and grade of adverse event and will use CTCAE v. 4.0
measure: Tumor response rate
time frame: 12 weeks
description: Objective response will be evaluated with computed tomography (CT) of the neck, chest and abdomen at baseline and post-treatment using RECIST 1.1 criteria.
arm group label: Group 1
arm group type: Experimental
description: Group 1 will be treated with Regimen A, followed by Regimen B. Regimen A is pembrolizumab, ASA and clopidogrel daily for 6 weeks. Regimen B is pembrolizumab alone for 6 weeks.
arm group label: Group 2
arm group type: Experimental
description: Group 2 will be treated with Regimen B, followed by Regimen A. Regimen B is pembrolizumab alone for 6 weeks. Regimen A is pembrolizumab, ASA and clopidogrel daily for 6 weeks.
intervention type: Drug
intervention name: Pembrolizumab
description: 200mg intravenous (IV) over 30 minutes
arm group label: Group 1
arm group label: Group 2
other name: Keytruda
intervention type: Drug
intervention name: Clopidogrel
description: 75mg/day oral
arm group label: Group 1
arm group label: Group 2
other name: Plavix
intervention type: Drug
intervention name: acetylsalicylic acid
description: 81mg/day oral
arm group label: Group 1
arm group label: Group 2
other name: ASA
other name: aspirin
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: John Kaczmar, MD
role: Principal Investigator
affiliation: Medical University of South Carolina
last name: Christina Godwin
phone: 843-792-8876
email: hcc-clinical-trials@musc.edu
facility: 
status: Recruiting
contact: 
country: United States
responsible party type: Sponsor
mesh term: Carcinoma, Squamous Cell
mesh term: Squamous Cell Carcinoma of Head and Neck
mesh term: Aspirin
mesh term: Pembrolizumab
mesh term: Clopidogrel
sharing ipd: No