<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/NCT02262741</url>
  </required_header>
  <id_info>
    <org_study_id>D4190C00011</org_study_id>
    <nct_id>NCT02262741</nct_id>
  </id_info>
  <brief_title>A Phase I Study to Evaluate the Safety, Tolerability and Efficacy of MEDI4736 (Durvalumab) With Tremelimumab in Head and Neck Cancer</brief_title>
  <official_title>A Phase I Study to Evaluate the Safety, Tolerability, and Efficacy of MEDI4736 in Combination With Tremelimumab in Subjects With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>MedImmune LLC</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>MedImmune LLC</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a multicenter, open-label, dose-exploration and dose-expansion study to evaluate the&#xD;
      safety, tolerability, antitumor activity, PK, pharmacodynamics, and immunogenicity of&#xD;
      MEDI4736 in combination with tremelimumab in subjects with recurrent/metastatic squamous cell&#xD;
      carcinoma of the head and neck.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 15, 2014</start_date>
  <completion_date type="Actual">September 21, 2017</completion_date>
  <primary_completion_date type="Actual">September 21, 2017</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>Number of subjects reporting adverse events</measure>
    <time_frame>Screening through 3 months after the last dose of study medication</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of subjects reporting serious adverse events</measure>
    <time_frame>Screening through 3 months after the last dose of study medication</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of subjects experiencing dose-limiting toxicities</measure>
    <time_frame>First dose of study medications through 4 weeks after the first dose of study medication</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from Baseline in laboratory evaluations</measure>
    <time_frame>Screening through 3 months after the last dose of study medication</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from Baseline in electrocardiograms</measure>
    <time_frame>Screening through 3 months through last dose of study medication</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from Baseline in vital signs</measure>
    <time_frame>Screening through 3 months after the last dose of study medication</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate</measure>
    <time_frame>Screening through 5 years after the last subject receives the first dose of study medication</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Individual MEDI4736 concentrations</measure>
    <time_frame>First dose of MEDI4736 through 3 months after the last dose of study medication</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects that develop changes in detectable antidrug antibodies to MEDI4736</measure>
    <time_frame>First dose of MEDI4736 through 6 months after the last dose of study medication</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease Control Rate</measure>
    <time_frame>Screening through 5 years after the last subject receives the first dose of study medication</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response</measure>
    <time_frame>Screening through 5 years after the last subject receives the first dose of study medication</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival</measure>
    <time_frame>Screening through 5 years after the last subject receives the first dose of study medication</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>Screening through 5 years after the last subject receives the first dose of study medication</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Individual tremelimumab concentrations</measure>
    <time_frame>First dose of tremelimumab through 3 months after the last dose of study medication</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MEDI4736 area under the concentration-curve</measure>
    <time_frame>First dose of MEDI4736 through 3 months after the last dose of study medication</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tremelimumab area under the concentration-curve</measure>
    <time_frame>First dose of tremelimumb through 3 months after the last dose of study medication</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects that develop changes in detectable antidrug antibodies to tremelimumab</measure>
    <time_frame>First dose of tremelimumab through 6 months after the last dose of study medication</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Changes in Biomarkers</measure>
    <time_frame>Screening through 3 months after the last patient receives the first dose of study medication</time_frame>
    <description>Evaluate biomarkers that may correlate with clinical activity of MEDI4736 monotherapy and in combination with tremelimumab</description>
  </other_outcome>
  <other_outcome>
    <measure>Change from Baseline in Patient-Reported Outcomes</measure>
    <time_frame>Screening through 5 years after the last patient receives the first dose of study medication</time_frame>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">71</enrollment>
  <condition>Squamous Cell Carcinoma of the Head and Neck</condition>
  <arm_group>
    <arm_group_label>MEDI4736 + tremelimumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>MEDI4736</intervention_name>
    <description>MEDI4736 will be administered by IV infusion in combination with tremelimumab.</description>
    <arm_group_label>MEDI4736 + tremelimumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>tremelimumab</intervention_name>
    <description>Tremelimumab will be administered by IV infusion in combination with MEDI4736.</description>
    <arm_group_label>MEDI4736 + tremelimumab</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male and female subjects&#xD;
&#xD;
          2. 18 years and older&#xD;
&#xD;
          3. Histologically or cytologically confirmed recurrent or metastatic squamous cell&#xD;
             carcinoma of the head and neck (oral cavity, oropharynx, hypopharynx or larynx) that&#xD;
             is incurable by local therapy.&#xD;
&#xD;
          4. Subjects who are treatment-naive or pretreated (prior anti-PD-1 or anti-PD-L1&#xD;
             required) in the recurrent/metastatic setting.&#xD;
&#xD;
          5. Subject eligibility will be based on PD-L1 expression as determined by a specified IHC&#xD;
             assay.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Any concurrent chemotherapy, immunotherapy, biologic, or hormonal therapy for cancer&#xD;
             treatment, receipt of last dose of an approved anticancer therapy within 21 days&#xD;
&#xD;
          2. Concurrent or prior use of immunosuppressive medication within 14 days&#xD;
&#xD;
          3. Active or prior documented autoimmune or inflammatory disease within 3 years with some&#xD;
             exceptions.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>99 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>MedImmune LLC</last_name>
    <role>Study Director</role>
    <affiliation>MedImmune LLC</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Scottsdale</city>
        <state>Arizona</state>
        <zip>85258</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>La Jolla</city>
        <state>California</state>
        <zip>92093</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90025</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90095</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94143</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06520</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32806</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Fairway</city>
        <state>Kansas</state>
        <zip>66205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>New Orleans</city>
        <state>Louisiana</state>
        <zip>70112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21287</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55455</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19111</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Greenville</city>
        <state>South Carolina</state>
        <zip>29605</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Fairfax</city>
        <state>Virginia</state>
        <zip>22031</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>London</city>
        <state>Ontario</state>
        <zip>N6A 4L6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G 2M9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2017</verification_date>
  <study_first_submitted>October 2, 2014</study_first_submitted>
  <study_first_submitted_qc>October 9, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 13, 2014</study_first_posted>
  <last_update_submitted>October 20, 2017</last_update_submitted>
  <last_update_submitted_qc>October 20, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">October 23, 2017</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</mesh_term>
    <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>Durvalumab</mesh_term>
    <mesh_term>Tremelimumab</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/NCT02262741
org study id: D4190C00011
nct id: NCT02262741
lead sponsor: 
has dmc: No
This is a multicenter, open-label, dose-exploration and dose-expansion study to evaluate the
      safety, tolerability, antitumor activity, PK, pharmacodynamics, and immunogenicity of
      MEDI4736 in combination with tremelimumab in subjects with recurrent/metastatic squamous cell
      carcinoma of the head and neck.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of subjects reporting adverse events
time frame: Screening through 3 months after the last dose of study medication
measure: Number of subjects reporting serious adverse events
time frame: Screening through 3 months after the last dose of study medication
measure: Number of subjects experiencing dose-limiting toxicities
time frame: First dose of study medications through 4 weeks after the first dose of study medication
measure: Change from Baseline in laboratory evaluations
time frame: Screening through 3 months after the last dose of study medication
measure: Change from Baseline in electrocardiograms
time frame: Screening through 3 months through last dose of study medication
measure: Change from Baseline in vital signs
time frame: Screening through 3 months after the last dose of study medication
measure: Objective Response Rate
time frame: Screening through 5 years after the last subject receives the first dose of study medication
measure: Individual MEDI4736 concentrations
time frame: First dose of MEDI4736 through 3 months after the last dose of study medication
measure: Number of subjects that develop changes in detectable antidrug antibodies to MEDI4736
time frame: First dose of MEDI4736 through 6 months after the last dose of study medication
measure: Disease Control Rate
time frame: Screening through 5 years after the last subject receives the first dose of study medication
measure: Duration of Response
time frame: Screening through 5 years after the last subject receives the first dose of study medication
measure: Progression Free Survival
time frame: Screening through 5 years after the last subject receives the first dose of study medication
measure: Overall Survival
time frame: Screening through 5 years after the last subject receives the first dose of study medication
measure: Individual tremelimumab concentrations
time frame: First dose of tremelimumab through 3 months after the last dose of study medication
measure: MEDI4736 area under the concentration-curve
time frame: First dose of MEDI4736 through 3 months after the last dose of study medication
measure: Tremelimumab area under the concentration-curve
time frame: First dose of tremelimumb through 3 months after the last dose of study medication
measure: Number of subjects that develop changes in detectable antidrug antibodies to tremelimumab
time frame: First dose of tremelimumab through 6 months after the last dose of study medication
measure: Changes in Biomarkers
time frame: Screening through 3 months after the last patient receives the first dose of study medication
description: Evaluate biomarkers that may correlate with clinical activity of MEDI4736 monotherapy and in combination with tremelimumab
measure: Change from Baseline in Patient-Reported Outcomes
time frame: Screening through 5 years after the last patient receives the first dose of study medication
arm group label: MEDI4736 + tremelimumab
arm group type: Experimental
intervention type: Biological
intervention name: MEDI4736
description: MEDI4736 will be administered by IV infusion in combination with tremelimumab.
arm group label: MEDI4736 + tremelimumab
intervention type: Biological
intervention name: tremelimumab
description: Tremelimumab will be administered by IV infusion in combination with MEDI4736.
arm group label: MEDI4736 + tremelimumab
criteria: 
gender: All
minimum age: 18 Years
maximum age: 99 Years
healthy volunteers: No
last name: MedImmune LLC
role: Study Director
affiliation: MedImmune LLC
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country: Canada
country: United States
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Squamous Cell
mesh term: Squamous Cell Carcinoma of Head and Neck
mesh term: Durvalumab
mesh term: Tremelimumab