<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/NCT03769311</url>
  </required_header>
  <id_info>
    <org_study_id>UW18098</org_study_id>
    <secondary_id>P50DE026787</secondary_id>
    <secondary_id>NCI-2018-02990</secondary_id>
    <secondary_id>2018-1232</secondary_id>
    <secondary_id>A534260</secondary_id>
    <secondary_id>SMPH/MEDICINE/HEM-ONC</secondary_id>
    <secondary_id>Protocol Version 6/26/2020</secondary_id>
    <nct_id>NCT03769311</nct_id>
  </id_info>
  <brief_title>Cetuximab in Head and Neck Cancer Patients</brief_title>
  <official_title>A Window of Opportunity Trial of Cetuximab in Patients With Head and Neck Squamous Cell Carcinoma (HNSCC)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Wisconsin, Madison</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute of Dental and Craniofacial Research (NIDCR)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>American Cancer Society, Inc.</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Wisconsin, Madison</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 clinical trial is for participants with head and neck squamous cell carcinoma who are&#xD;
      scheduled to have their tumor surgically removed. The study involves obtaining baseline&#xD;
      tissue from a clinical biopsy or research biopsy and measurement of circulating tumor cells&#xD;
      before surgery to determine whether AXL protein expression pre-treatment correlates to&#xD;
      clinical outcomes (change in tumor size) after two doses of cetuximab. The importance of this&#xD;
      study is to describe if AXL expression can be used as a biomarker to predict clinical&#xD;
      response to cetuximab (CTX) treatment.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a window of opportunity trial evaluating the hypothesis that AXL levels correlate&#xD;
      with clinical response to cetuximab in head and neck patients. Patients with head and neck&#xD;
      squamous cell carcinoma who are scheduled to undergo surgical resection of their tumor and&#xD;
      are candidates for cetuximab chemotherapy are eligible to participate.&#xD;
&#xD;
      Primary:&#xD;
&#xD;
      1. To test the hypothesis that low AXL correlates with clinical response to cetuximab in head&#xD;
      and neck cancer patients&#xD;
&#xD;
      Secondary:&#xD;
&#xD;
      1. To further describe the safety of pre-operative administration of cetuximab&#xD;
&#xD;
      Correlative:&#xD;
&#xD;
        1. To correlate AXL expression with change in Ki67 following cetuximab in Head and Neck&#xD;
           Cancer (HNC) patients&#xD;
&#xD;
        2. To examine other putative markers of cetuximab sensitivity such as HER3 and change in&#xD;
           circulating tumor cells&#xD;
&#xD;
        3. To establish the first panel of patient-derived xenografts from patients with known&#xD;
           sensitivity or resistance to cetuximab&#xD;
&#xD;
      Following informed consent, tumor tissue from the research biopsy and a blood draw for&#xD;
      circulating tumor cells will be obtained. The participant will then receive two weekly doses&#xD;
      of pre-operative cetuximab during the interval between diagnostic biopsy and surgery (~14&#xD;
      days), ensuring that no delay in standard of care (SOC) will occur.&#xD;
&#xD;
      For dose #1, participants will receive cetuximab 400 mg/m2 via intravenous infusion over 2&#xD;
      hours (maximum infusion rate 10 mg/min) as per the standard of care loading regimen for&#xD;
      cetuximab monotherapy.&#xD;
&#xD;
      For dose #2, participants will receive cetuximab 250 mg/m2 via intravenous infusion over 1&#xD;
      hour (maximum infusion rate 10 mg/min) as per the standard of care dosing regimen for&#xD;
      cetuximab monotherapy.&#xD;
&#xD;
      At the time of surgery, another blood draw will be obtained for analysis of circulating tumor&#xD;
      cells, and a portion of the resected tumor will be obtained for study analysis.&#xD;
&#xD;
      Correlative studies will include the measurement of proteins hypothesized to be involved in&#xD;
      cetuximab resistance such as AXL, Ki67, EGFR, and HER3 expression from both the biopsy and&#xD;
      the surgical specimen. Blood will be analyzed for correlative analysis of circulating tumor&#xD;
      cells. Tissue from the research biopsy will be utilized for participant-derived xenograft&#xD;
      (PDX) development.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 17, 2019</start_date>
  <completion_date type="Actual">March 15, 2022</completion_date>
  <primary_completion_date type="Actual">March 15, 2022</primary_completion_date>
  <phase>Phase 2</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>
    <intervention_model_description>Single site, open label, window of opportunity study</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Tumor Size</measure>
    <time_frame>up to 42 days</time_frame>
    <description>The tumor size (via clinical measurements) will be measured from the time of diagnosis (pre-CTX) to after treatment with 2 doses of cetuximab and within 48 hours prior to surgery (post-CTX). Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 Committee criteria will be used to define clinical response (partial response, progressive disease, or stable disease) prior to surgery.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Objective Tumor Response Rate - AXL Expression</measure>
    <time_frame>up to 42 days</time_frame>
    <description>The levels of AXL expression (low vs high, ranges from 0-4+ with 4+ meaning intense staining in the majority of cancer cells and 0 meaning no staining at all) at the time of diagnosis (pre-CTX) will measured and compared to change in the tumor size as reported in Primary Outcome Measure 1.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Hospital Re-admission for CTX-related Complications</measure>
    <time_frame>within 28 days after surgery</time_frame>
    <description>Hospital re-admission for wound healing, surgical complications, or infection that occur within 28 days after surgery will be categorized as definitely related, probably related, possibility related, unlikely related, or unrelated to cetuximab administration and will be reported as a number of participants.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Change in Ki67 From Pre- vs Post-CTX Treated Tumors</measure>
    <time_frame>up to 30 months</time_frame>
    <description>Summary statistics of the change in Ki67 (ΔKi67), as established by the surgical specimen, will be reported for the response to cetuximab endpoint.</description>
  </other_outcome>
  <other_outcome>
    <measure>Correlation of Measures of Putative Markers of CTX Sensitivity</measure>
    <time_frame>up to 30 months</time_frame>
    <description>Markers include: protein, RNA, circulating tumor cells with CTX response, measured by Ki67. Correlation between ΔKi67 and putative biomarkers will be analyzed as a continuous variable and will be tested using Pearson's correlation coefficient. Correlation between two biomarkers such as AXL and HER3 expression as continuous variables will be investigated using Pearson's correlation coefficient. Summary statistics will be used to report circulating tumor cells at each time point and the changes between time points. The association of change in circulating tumor cells with ΔKi67 (early response) will be explored graphically and with Pearson's correlation coefficient.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">15</enrollment>
  <condition>Head and Neck Cancer</condition>
  <condition>Squamous Cell Carcinoma</condition>
  <arm_group>
    <arm_group_label>Pre-Operative Cetuximab Therapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Two weekly doses of pre-operative cetuximab during the interval between diagnostic HNSCC biopsy and surgery (~14 days), ensuring that no delay in standard of care (SOC) will occur. For dose #1, participants will receive cetuximab 400 mg/m2 via intravenous infusion over 2 hours (maximum infusion rate 10 mg/min) as per the standard of care loading regimen for cetuximab monotherapy. For dose #2, participants will receive cetuximab 250 mg/m2 via intravenous infusion over 1 hour (maximum infusion rate 10 mg/min) as per the standard of care dosing regimen for cetuximab monotherapy.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cetuximab</intervention_name>
    <description>Monoclonal antibody against epidermal growth factor receptor (EGFR)</description>
    <arm_group_label>Pre-Operative Cetuximab Therapy</arm_group_label>
    <other_name>CTX</other_name>
    <other_name>Erbitux</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Informed consent: participants must be informed of the investigational nature of the study&#xD;
        and must be able to sign a written informed consent.&#xD;
&#xD;
          -  Inclusion criteria for research biopsy (screen)&#xD;
&#xD;
               -  Participants must have suspected or known clinical presentation of head and neck&#xD;
                  squamous cell carcinoma or a recurrence of head and neck squamous cell carcinoma&#xD;
                  after initial therapy. For newly suspected head and neck cancer, the procedure&#xD;
                  will obtain tissue for both standard of care biopsy and additional tissue for&#xD;
                  research.&#xD;
&#xD;
               -  Participants must have sufficient tumor volume (approximately 10 cc) to&#xD;
                  accommodate at minimum 2-3 core samples for the research biopsy. This will be&#xD;
                  approximated based on clinical evidence, such as physician visualization or&#xD;
                  palpitation.&#xD;
&#xD;
               -  Participants are required to consent to the TSB Biobank protocol (2016-0934) as&#xD;
                  part of this study.&#xD;
&#xD;
               -  Surgical management must be the chosen modality for management of the head and&#xD;
                  neck squamous cell cancer.&#xD;
&#xD;
                    -  Other therapeutic modalities may follow, but surgery must be the choice for&#xD;
                       first therapy rendered.&#xD;
&#xD;
          -  Inclusion criteria for cetuximab treatment:&#xD;
&#xD;
               -  Participants must have a biopsy proven, squamous cell carcinoma of the head and&#xD;
                  neck, excluding advanced cutaneous head and neck squamous cell carcinoma.&#xD;
&#xD;
               -  ECOG performance status £ 1&#xD;
&#xD;
               -  Women of childbearing potential (WOCP) must not be pregnant (confirmed by a&#xD;
                  negative urine/serum pregnancy test within 7 days of cetuximab treatment). In&#xD;
                  addition, a medically acceptable method of birth control must be used such as an&#xD;
                  oral, implantable, injectable, or transdermal hormonal contraceptive, an&#xD;
                  intrauterine device (IUD), use of a double barrier method (condoms, sponge,&#xD;
                  diaphragm, or vaginal ring with spermicidal jellies or cream), or total&#xD;
                  abstinence during the study participation and for 6 months after last dose of&#xD;
                  study drug. Women who are postmenopausal for at least 1 year or surgically&#xD;
                  sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy) are&#xD;
                  not considered to be WOCP.&#xD;
&#xD;
               -  Men who are not surgically or medically sterile must agree to use an acceptable&#xD;
                  method of contraception. Male participants with female sexual partners who are&#xD;
                  pregnant, possibly pregnant, or who could become pregnant must agree to use&#xD;
                  condoms during the study and for 6 months post study drug. Total abstinence for&#xD;
                  the same study period is an acceptable alternative.&#xD;
&#xD;
               -  Participants with other concomitant malignancies are allowed to participate on&#xD;
                  the clinical trial as long as the surgical resection of the head and neck&#xD;
                  squamous cell carcinoma is clinically indicated.&#xD;
&#xD;
               -  Participants with metastatic disease are allowed to participate on the clinical&#xD;
                  as long as the surgical resection of the head and neck squamous cell carcinoma is&#xD;
                  clinically indicated.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of nasopharyngeal carcinoma, advanced cutaneous squamous cell carcinoma of&#xD;
             the head &amp; neck, and salivary gland tumors&#xD;
&#xD;
          -  Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g.&#xD;
             active or uncontrolled infection, uncontrolled diabetes) that could cause unacceptable&#xD;
             safety risks or compromise compliance with the protocol&#xD;
&#xD;
          -  Prior chemotherapy, radiotherapy, or major surgery within 8 weeks of study enrollment&#xD;
             or those who have not recovered (to grade ≤ 1 or baseline) from clinically significant&#xD;
             adverse events due to agents administered more than 8 weeks earlier (alopecia and&#xD;
             fatigue excluded). Clinical significance to be determined by the study investigator&#xD;
&#xD;
          -  Prior cetuximab therapy is allowed so long as administered ³ 8 weeks ago.&#xD;
&#xD;
          -  History of allergic reactions attributed to compounds of chemical or biologic&#xD;
             composition similar to those of cetuximab&#xD;
&#xD;
          -  Pregnancy, breastfeeding, or expecting to conceive or father children within the&#xD;
             projected duration of the trial, starting with the screening visit through 6 months&#xD;
             after the last dose of trial treatment&#xD;
&#xD;
          -  Ongoing or active infection, including active tuberculosis or known infection with the&#xD;
             human immunodeficiency virus (HIV)&#xD;
&#xD;
          -  Ongoing treatment with other investigational agents.&#xD;
&#xD;
          -  Any of the following cardiac conditions:&#xD;
&#xD;
               -  uncontrolled or poorly-controlled arrhythmia or uncontrolled cardiac&#xD;
                  insufficiency uncontrolled or poorly-controlled hypertension (&gt;180 mmHg systolic&#xD;
                  or &gt; 130 mmHg diastolic)&#xD;
&#xD;
          -  Any of the following conditions:&#xD;
&#xD;
               -  serious or non-healing wound, ulcer, or bone fracture&#xD;
&#xD;
               -  history of abdominal fistula, gastrointestinal perforation, or intraabdominal&#xD;
                  abscess within 28 days of study enrollment&#xD;
&#xD;
               -  history of cerebrovascular accident (CVA) or transient ischemic attack within 12&#xD;
                  months prior to study enrollment&#xD;
&#xD;
               -  history of myocardial infarction, ventricular arrhythmia, stable/unstable angina,&#xD;
                  symptomatic congestive heart failure, coronary/peripheral artery bypass graft or&#xD;
                  stenting or other significant cardiac disease within 6 months prior to study&#xD;
                  enrollment&#xD;
&#xD;
               -  history of arterial or venous thrombosis/thromboembolic event, including&#xD;
                  pulmonary embolism within 6 months of study enrollment&#xD;
&#xD;
               -  any condition requiring the use of immunosuppression, excluding rheumatologic&#xD;
                  conditions treated with stable doses of corticosteroids&#xD;
&#xD;
               -  Use of herbal supplements (St. John's Wort, gingko biloba, etc.) within one week&#xD;
                  of cetuximab treatment&#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>Justine Bruce</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Wisconsin, Madison</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Wisconsin Carbone Cancer Center</name>
      <address>
        <city>Madison</city>
        <state>Wisconsin</state>
        <zip>53792</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://cancer.wisc.edu/</url>
    <description>University of Wisconsin Carbone Cancer Center</description>
  </link>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>November 28, 2018</study_first_submitted>
  <study_first_submitted_qc>December 5, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 7, 2018</study_first_posted>
  <results_first_submitted>March 15, 2023</results_first_submitted>
  <results_first_submitted_qc>May 2, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">May 24, 2023</results_first_posted>
  <last_update_submitted>May 2, 2023</last_update_submitted>
  <last_update_submitted_qc>May 2, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 24, 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</mesh_term>
    <mesh_term>Carcinoma, Squamous Cell</mesh_term>
    <mesh_term>Head and Neck Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cetuximab</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>June 26, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/11/NCT03769311/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants were recruited from the University of Wisconsin Carbone Cancer Center from April 2019 to March 2021.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Pre-Operative Cetuximab Therapy</title>
          <description>Two weekly doses of pre-operative cetuximab during the interval between diagnostic HNSCC biopsy and surgery (~14 days), ensuring that no delay in standard of care (SOC) will occur. For dose #1, participants will receive cetuximab 400 mg/m2 via intravenous infusion over 2 hours (maximum infusion rate 10 mg/min) as per the standard of care loading regimen for cetuximab monotherapy. For dose #2, participants will receive cetuximab 250 mg/m2 via intravenous infusion over 1 hour (maximum infusion rate 10 mg/min) as per the standard of care dosing regimen for cetuximab monotherapy.&#xD;
Cetuximab: Monoclonal antibody against epidermal growth factor receptor (EGFR)</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Pre-Operative Cetuximab Therapy</title>
          <description>Two weekly doses of pre-operative cetuximab during the interval between diagnostic HNSCC biopsy and surgery (~14 days), ensuring that no delay in standard of care (SOC) will occur. For dose #1, participants will receive cetuximab 400 mg/m2 via intravenous infusion over 2 hours (maximum infusion rate 10 mg/min) as per the standard of care loading regimen for cetuximab monotherapy. For dose #2, participants will receive cetuximab 250 mg/m2 via intravenous infusion over 1 hour (maximum infusion rate 10 mg/min) as per the standard of care dosing regimen for cetuximab monotherapy.&#xD;
Cetuximab: Monoclonal antibody against epidermal growth factor receptor (EGFR)</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="15"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>20-29</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>30-39</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>40-49</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>50-59</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>60-69</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>70-79</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>80-89</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Disease Site</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Floor of Mouth</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Tongue</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Tonsil</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Soft Palate</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Other, unspecified parts of mouth</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Tumor Size</title>
        <description>The tumor size (via clinical measurements) will be measured from the time of diagnosis (pre-CTX) to after treatment with 2 doses of cetuximab and within 48 hours prior to surgery (post-CTX). Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 Committee criteria will be used to define clinical response (partial response, progressive disease, or stable disease) prior to surgery.</description>
        <time_frame>up to 42 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Pre-Operative Cetuximab Therapy</title>
            <description>Two weekly doses of pre-operative cetuximab during the interval between diagnostic HNSCC biopsy and surgery (~14 days), ensuring that no delay in standard of care (SOC) will occur. For dose #1, participants will receive cetuximab 400 mg/m2 via intravenous infusion over 2 hours (maximum infusion rate 10 mg/min) as per the standard of care loading regimen for cetuximab monotherapy. For dose #2, participants will receive cetuximab 250 mg/m2 via intravenous infusion over 1 hour (maximum infusion rate 10 mg/min) as per the standard of care dosing regimen for cetuximab monotherapy.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Tumor Size</title>
          <description>The tumor size (via clinical measurements) will be measured from the time of diagnosis (pre-CTX) to after treatment with 2 doses of cetuximab and within 48 hours prior to surgery (post-CTX). Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 Committee criteria will be used to define clinical response (partial response, progressive disease, or stable disease) prior to surgery.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Partial response</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Progressive disease</title>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Stable disease</title>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Objective Tumor Response Rate - AXL Expression</title>
        <description>The levels of AXL expression (low vs high, ranges from 0-4+ with 4+ meaning intense staining in the majority of cancer cells and 0 meaning no staining at all) at the time of diagnosis (pre-CTX) will measured and compared to change in the tumor size as reported in Primary Outcome Measure 1.</description>
        <time_frame>up to 42 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Pre-Operative Cetuximab Therapy</title>
            <description>Two weekly doses of pre-operative cetuximab during the interval between diagnostic HNSCC biopsy and surgery (~14 days), ensuring that no delay in standard of care (SOC) will occur. For dose #1, participants will receive cetuximab 400 mg/m2 via intravenous infusion over 2 hours (maximum infusion rate 10 mg/min) as per the standard of care loading regimen for cetuximab monotherapy. For dose #2, participants will receive cetuximab 250 mg/m2 via intravenous infusion over 1 hour (maximum infusion rate 10 mg/min) as per the standard of care dosing regimen for cetuximab monotherapy.</description>
          </group>
        </group_list>
        <measure>
          <title>Objective Tumor Response Rate - AXL Expression</title>
          <description>The levels of AXL expression (low vs high, ranges from 0-4+ with 4+ meaning intense staining in the majority of cancer cells and 0 meaning no staining at all) at the time of diagnosis (pre-CTX) will measured and compared to change in the tumor size as reported in Primary Outcome Measure 1.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.3" lower_limit="1" upper_limit="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Hospital Re-admission for CTX-related Complications</title>
        <description>Hospital re-admission for wound healing, surgical complications, or infection that occur within 28 days after surgery will be categorized as definitely related, probably related, possibility related, unlikely related, or unrelated to cetuximab administration and will be reported as a number of participants.</description>
        <time_frame>within 28 days after surgery</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Pre-Operative Cetuximab Therapy</title>
            <description>Two weekly doses of pre-operative cetuximab during the interval between diagnostic HNSCC biopsy and surgery (~14 days), ensuring that no delay in standard of care (SOC) will occur. For dose #1, participants will receive cetuximab 400 mg/m2 via intravenous infusion over 2 hours (maximum infusion rate 10 mg/min) as per the standard of care loading regimen for cetuximab monotherapy. For dose #2, participants will receive cetuximab 250 mg/m2 via intravenous infusion over 1 hour (maximum infusion rate 10 mg/min) as per the standard of care dosing regimen for cetuximab monotherapy.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Hospital Re-admission for CTX-related Complications</title>
          <description>Hospital re-admission for wound healing, surgical complications, or infection that occur within 28 days after surgery will be categorized as definitely related, probably related, possibility related, unlikely related, or unrelated to cetuximab administration and will be reported as a number of participants.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Change in Ki67 From Pre- vs Post-CTX Treated Tumors</title>
        <description>Summary statistics of the change in Ki67 (ΔKi67), as established by the surgical specimen, will be reported for the response to cetuximab endpoint.</description>
        <time_frame>up to 30 months</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Correlation of Measures of Putative Markers of CTX Sensitivity</title>
        <description>Markers include: protein, RNA, circulating tumor cells with CTX response, measured by Ki67. Correlation between ΔKi67 and putative biomarkers will be analyzed as a continuous variable and will be tested using Pearson's correlation coefficient. Correlation between two biomarkers such as AXL and HER3 expression as continuous variables will be investigated using Pearson's correlation coefficient. Summary statistics will be used to report circulating tumor cells at each time point and the changes between time points. The association of change in circulating tumor cells with ΔKi67 (early response) will be explored graphically and with Pearson's correlation coefficient.</description>
        <time_frame>up to 30 months</time_frame>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>All AE's will be recorded from the time of informed consent until 28 days past last dose of study drug or day of surgery, whichever is first. SAE's will be recorded from the time of informed consent through 28 days past last dose of study drug or 28 days post-surgery, whichever is later. Up to 10 weeks on study.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Pre-Operative Cetuximab Therapy</title>
          <description>Two weekly doses of pre-operative cetuximab during the interval between diagnostic HNSCC biopsy and surgery (~14 days), ensuring that no delay in standard of care (SOC) will occur. For dose #1, participants will receive cetuximab 400 mg/m2 via intravenous infusion over 2 hours (maximum infusion rate 10 mg/min) as per the standard of care loading regimen for cetuximab monotherapy. For dose #2, participants will receive cetuximab 250 mg/m2 via intravenous infusion over 1 hour (maximum infusion rate 10 mg/min) as per the standard of care dosing regimen for cetuximab monotherapy.&#xD;
Cetuximab: Monoclonal antibody against epidermal growth factor receptor (EGFR)</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>CTCAE v5.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Oral Pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hypomagnesemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Joint Aches</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Muscle Twitching</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Tumor Hemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Maculo-papular rash</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Justine Bruce, MD</name_or_title>
      <organization>University of Wisconsin Carbone Cancer Center</organization>
      <phone>608-262-4961</phone>
      <email>jybruce@medicine.wisc.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03769311
org study id: UW18098
secondary id: P50DE026787
secondary id: NCI-2018-02990
secondary id: 2018-1232
secondary id: A534260
secondary id: SMPH/MEDICINE/HEM-ONC
secondary id: Protocol Version 6/26/2020
nct id: NCT03769311
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This clinical trial is for participants with head and neck squamous cell carcinoma who are
      scheduled to have their tumor surgically removed. The study involves obtaining baseline
      tissue from a clinical biopsy or research biopsy and measurement of circulating tumor cells
      before surgery to determine whether AXL protein expression pre-treatment correlates to
      clinical outcomes (change in tumor size) after two doses of cetuximab. The importance of this
      study is to describe if AXL expression can be used as a biomarker to predict clinical
      response to cetuximab (CTX) treatment.
This is a window of opportunity trial evaluating the hypothesis that AXL levels correlate
      with clinical response to cetuximab in head and neck patients. Patients with head and neck
      squamous cell carcinoma who are scheduled to undergo surgical resection of their tumor and
      are candidates for cetuximab chemotherapy are eligible to participate.

      Primary:

      1. To test the hypothesis that low AXL correlates with clinical response to cetuximab in head
      and neck cancer patients

      Secondary:

      1. To further describe the safety of pre-operative administration of cetuximab

      Correlative:

        1. To correlate AXL expression with change in Ki67 following cetuximab in Head and Neck
           Cancer (HNC) patients

        2. To examine other putative markers of cetuximab sensitivity such as HER3 and change in
           circulating tumor cells

        3. To establish the first panel of patient-derived xenografts from patients with known
           sensitivity or resistance to cetuximab

      Following informed consent, tumor tissue from the research biopsy and a blood draw for
      circulating tumor cells will be obtained. The participant will then receive two weekly doses
      of pre-operative cetuximab during the interval between diagnostic biopsy and surgery (~14
      days), ensuring that no delay in standard of care (SOC) will occur.

      For dose #1, participants will receive cetuximab 400 mg/m2 via intravenous infusion over 2
      hours (maximum infusion rate 10 mg/min) as per the standard of care loading regimen for
      cetuximab monotherapy.

      For dose #2, participants will receive cetuximab 250 mg/m2 via intravenous infusion over 1
      hour (maximum infusion rate 10 mg/min) as per the standard of care dosing regimen for
      cetuximab monotherapy.

      At the time of surgery, another blood draw will be obtained for analysis of circulating tumor
      cells, and a portion of the resected tumor will be obtained for study analysis.

      Correlative studies will include the measurement of proteins hypothesized to be involved in
      cetuximab resistance such as AXL, Ki67, EGFR, and HER3 expression from both the biopsy and
      the surgical specimen. Blood will be analyzed for correlative analysis of circulating tumor
      cells. Tissue from the research biopsy will be utilized for participant-derived xenograft
      (PDX) development.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Single site, open label, window of opportunity study
primary purpose: Treatment
masking: None (Open Label)
measure: Change in Tumor Size
time frame: up to 42 days
description: The tumor size (via clinical measurements) will be measured from the time of diagnosis (pre-CTX) to after treatment with 2 doses of cetuximab and within 48 hours prior to surgery (post-CTX). Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 Committee criteria will be used to define clinical response (partial response, progressive disease, or stable disease) prior to surgery.
measure: Objective Tumor Response Rate - AXL Expression
time frame: up to 42 days
description: The levels of AXL expression (low vs high, ranges from 0-4+ with 4+ meaning intense staining in the majority of cancer cells and 0 meaning no staining at all) at the time of diagnosis (pre-CTX) will measured and compared to change in the tumor size as reported in Primary Outcome Measure 1.
measure: Number of Hospital Re-admission for CTX-related Complications
time frame: within 28 days after surgery
description: Hospital re-admission for wound healing, surgical complications, or infection that occur within 28 days after surgery will be categorized as definitely related, probably related, possibility related, unlikely related, or unrelated to cetuximab administration and will be reported as a number of participants.
measure: Change in Ki67 From Pre- vs Post-CTX Treated Tumors
time frame: up to 30 months
description: Summary statistics of the change in Ki67 (ΔKi67), as established by the surgical specimen, will be reported for the response to cetuximab endpoint.
measure: Correlation of Measures of Putative Markers of CTX Sensitivity
time frame: up to 30 months
description: Markers include: protein, RNA, circulating tumor cells with CTX response, measured by Ki67. Correlation between ΔKi67 and putative biomarkers will be analyzed as a continuous variable and will be tested using Pearson's correlation coefficient. Correlation between two biomarkers such as AXL and HER3 expression as continuous variables will be investigated using Pearson's correlation coefficient. Summary statistics will be used to report circulating tumor cells at each time point and the changes between time points. The association of change in circulating tumor cells with ΔKi67 (early response) will be explored graphically and with Pearson's correlation coefficient.
arm group label: Pre-Operative Cetuximab Therapy
arm group type: Experimental
description: Two weekly doses of pre-operative cetuximab during the interval between diagnostic HNSCC biopsy and surgery (~14 days), ensuring that no delay in standard of care (SOC) will occur. For dose #1, participants will receive cetuximab 400 mg/m2 via intravenous infusion over 2 hours (maximum infusion rate 10 mg/min) as per the standard of care loading regimen for cetuximab monotherapy. For dose #2, participants will receive cetuximab 250 mg/m2 via intravenous infusion over 1 hour (maximum infusion rate 10 mg/min) as per the standard of care dosing regimen for cetuximab monotherapy.
intervention type: Drug
intervention name: Cetuximab
description: Monoclonal antibody against epidermal growth factor receptor (EGFR)
arm group label: Pre-Operative Cetuximab Therapy
other name: CTX
other name: Erbitux
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Justine Bruce
role: Principal Investigator
affiliation: University of Wisconsin, Madison
facility: 
country: United States
url: https://cancer.wisc.edu/
description: University of Wisconsin Carbone Cancer Center
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Squamous Cell
mesh term: Head and Neck Neoplasms
mesh term: Cetuximab
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 