<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/NCT01696955</url>
  </required_header>
  <id_info>
    <org_study_id>NCI-2012-01640</org_study_id>
    <secondary_id>NCI-2012-01640</secondary_id>
    <secondary_id>12-1359</secondary_id>
    <secondary_id>478834</secondary_id>
    <secondary_id>9165</secondary_id>
    <secondary_id>9165</secondary_id>
    <secondary_id>N01CM00038</secondary_id>
    <secondary_id>N01CM00071</secondary_id>
    <secondary_id>N01CM00099</secondary_id>
    <secondary_id>P30CA014599</secondary_id>
    <nct_id>NCT01696955</nct_id>
  </id_info>
  <brief_title>Cetuximab With or Without Tivantinib in Treating Patients With Head and Neck Cancer That Is Recurrent, Metastatic, or Cannot Be Removed by Surgery</brief_title>
  <official_title>A Randomized Phase II Trial of ARQ 197 (Tivantinib)/Cetuximab Versus Cetuximab in Patients With Recurrent/Metastatic Head and Neck Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Cancer Institute (NCI)</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This randomized phase II trial studies how well cetuximab with or without tivantinib works in&#xD;
      treating patients with head and neck cancer that has come back (recurrent), has spread to&#xD;
      other places in the body (metastatic), or cannot be removed by surgery. Monoclonal&#xD;
      antibodies, such as cetuximab, may interfere with the ability of tumor cells to grow and&#xD;
      spread. Tivantinib may stop the growth of tumor cells by blocking some of the enzymes needed&#xD;
      for cell growth. It is not yet known whether cetuximab is more effective with or without&#xD;
      tivantinib in treating patients with head and neck cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. Response rate (comparing the cetuximab/ARQ 197 [tivantinib] combination with cetuximab&#xD;
      single agent activity).&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. Continuous tumor shrinkage. II. Progression-free survival (PFS). III. Overall survival&#xD;
      (OS). IV. Objectives I, II, and III above, as well as response rates, will be assessed and&#xD;
      compared between treatment arms in the subgroup of patients with high mesenchymal epithelial&#xD;
      transition factor (c-MET) expression, and/or high c-MET copy number.&#xD;
&#xD;
      V. Single agent activity for ARQ 197 (tivantinib) in patients who have failed cetuximab.&#xD;
&#xD;
      OUTLINE: Patients are randomized to 1 of 2 treatment arms.&#xD;
&#xD;
      ARM I: Patients receive cetuximab intravenously (IV) over 60-120 minutes on days 1 and 15 and&#xD;
      tivantinib orally (PO) twice daily (BID) on days 1-28. Courses repeat every 4 weeks in the&#xD;
      absence of disease progression or unacceptable toxicity.&#xD;
&#xD;
      ARM II: Patients receive cetuximab IV over 60-120 minutes on days 1 and 15. Patients who fail&#xD;
      cetuximab as a single agent may receive single agent tivantinib PO BID on days 1-28. Courses&#xD;
      repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up for 5 years.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 20, 2012</start_date>
  <completion_date type="Actual">May 5, 2017</completion_date>
  <primary_completion_date type="Actual">May 5, 2017</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Overall Response Rate</measure>
    <time_frame>Up to 1 year</time_frame>
    <description>Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), &gt;=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>c-MET Copy Number</measure>
    <time_frame>Baseline to 8 weeks</time_frame>
    <description>Change in copy number from baseline to 8 weeks</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>c-MET Expression</measure>
    <time_frame>Baseline to 8 weeks</time_frame>
    <description>Change in c-MET expression from baseline to 8 weeks</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Tumor Burden</measure>
    <time_frame>Baseline to 8 weeks</time_frame>
    <description>Early change in tumor burden measured using the sum of longest diameters of target lesions, expressed as percent change from baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Time from randomization until death or date last known alive</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free Survival</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>Time from randomization until disease progression/death from any cause or date last know progression-free</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Response Rate of Single-agent Tivantinib After Failure of Cetuximab</measure>
    <time_frame>Up to 1 year</time_frame>
    <description>Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), &gt;=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Number of Participants With Adverse Events While on Single-agent Tivantinib After Failure of Cetuximab</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>Non-serious adverse events, CTCAE (4.0)</description>
  </other_outcome>
  <other_outcome>
    <measure>Number of Patients With Serious Adverse Events While on Single-agent Tivantinib After Failure of Cetuximab</measure>
    <time_frame>3 years</time_frame>
    <description>CTCAE (4.0)</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">81</enrollment>
  <condition>Head and Neck Squamous Cell Carcinoma</condition>
  <condition>Recurrent Head and Neck Carcinoma</condition>
  <arm_group>
    <arm_group_label>Arm I (cetuximab and tivantinib)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive cetuximab IV over 60-120 minutes on days 1 and 15 and tivantinib PO BID on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm II (cetuximab)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive cetuximab IV over 60-120 minutes on days 1 and 15. Patients who fail cetuximab as a single agent may receive single agent tivantinib PO BID on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Cetuximab</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Arm I (cetuximab and tivantinib)</arm_group_label>
    <arm_group_label>Arm II (cetuximab)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Laboratory Biomarker Analysis</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Arm I (cetuximab and tivantinib)</arm_group_label>
    <arm_group_label>Arm II (cetuximab)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tivantinib</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Arm I (cetuximab and tivantinib)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histologically/cytologically confirmed diagnosis of squamous cell carcinoma of head&#xD;
             and neck origin not amenable to curative intent therapy; both human papillomavirus&#xD;
             (HPV) positive (+) and HPV negative (-) are eligible, but status has to be known prior&#xD;
             to randomization (although not required for consenting); any type of tissue based HPV&#xD;
             assessment is acceptable (e.g. p16 immunohistochemistry [IHC] or HPV in situ&#xD;
             hybridization [ISH]); if local HPV testing is not available slides can be sent to the&#xD;
             University of Chicago for HPV testing; please note that p16 IHC is generally only&#xD;
             considered to be accurate for oropharyngeal tumors&#xD;
&#xD;
          -  Presence of measurable lesions (as per Response Evaluation Criteria in Solid Tumors&#xD;
             [RECIST] 1.1); generally a &gt;= 10 mm tumor lesion (in the longest diameter by computed&#xD;
             tomography [CT] scan) or a lymph node &gt;= 15 mm (short axis) is considered measurable&#xD;
             disease when evaluated by CT scan (with a slice thickness no greater than 5 mm)&#xD;
&#xD;
          -  Availability of tissue (10 tumor containing formalin-fixed, paraffin-embedded [FFPE]&#xD;
             slides/sections)&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1&#xD;
&#xD;
          -  Patients who have received cetuximab or another inhibitor of epidermal growth factor&#xD;
             receptor (EGFR) in the curative intent treatment setting (e.g. with radiation or&#xD;
             during induction chemotherapy [prior to definitive, curative intent therapy]) are&#xD;
             eligible for the study&#xD;
&#xD;
          -  Life expectancy of greater than 8 weeks&#xD;
&#xD;
          -  Hemoglobin &gt;= 9.0 g/dL&#xD;
&#xD;
          -  Leukocytes &gt;= 3,000/mcL&#xD;
&#xD;
          -  Absolute neutrophil count &gt;= 1,500/mcL&#xD;
&#xD;
          -  Platelets &gt;= 100,000/mcL&#xD;
&#xD;
          -  Total bilirubin =&lt; 1.5 x institutional upper limit of normal&#xD;
&#xD;
          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase&#xD;
             [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])&#xD;
             =&lt; 2.5 x institutional upper limit of normal&#xD;
&#xD;
          -  Serum creatinine =&lt; 1.5 x institutional upper limit of normal OR creatinine clearance&#xD;
             &gt;= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal&#xD;
&#xD;
          -  Patients must be able to swallow ARQ 197 (tivantinib) by mouth, unless adequate data&#xD;
             about administration by gastrostomy (G)-tube becomes available; tablets may be&#xD;
             crushed, but must be taken orally&#xD;
&#xD;
          -  Human immunodeficiency virus (HIV)-positive patients with normal immune function&#xD;
             (cluster of differentiation [CD]4 count &gt; 200) are eligible if there are no drug&#xD;
             interactions with ARQ 197 (tivantinib) or cetuximab&#xD;
&#xD;
          -  Women of child-bearing potential and men must agree to use adequate contraception&#xD;
             (hormonal or barrier method of birth control; abstinence) prior to study entry and for&#xD;
             the duration of study participation; should a woman become pregnant or suspect she is&#xD;
             pregnant while she or her partner is participating in this study, she should inform&#xD;
             her treating physician immediately; men treated or enrolled on this protocol must also&#xD;
             agree to use adequate contraception prior to the study, for the duration of study&#xD;
             participation, and 4 months after completion of ARQ 197 (tivantinib) administration&#xD;
&#xD;
          -  Ability to understand and the willingness to sign a written informed consent document&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients who have had chemotherapy or radiotherapy within 2 weeks (6 weeks for&#xD;
             nitrosoureas or mitomycin C) prior to entering the study or those who have not&#xD;
             recovered from adverse events due to agents administered more than 2 weeks earlier&#xD;
&#xD;
          -  Nasopharyngeal tumors that show lymphoepithelioma histology&#xD;
&#xD;
          -  Patients who have received more than 2 prior cytotoxic treatments in the palliative&#xD;
             treatment setting are ineligible&#xD;
&#xD;
          -  Patients who have received treatment with an EGFR or MET inhibitor in the palliative&#xD;
             treatment setting are ineligible&#xD;
&#xD;
          -  Patients with known, active brain metastases should be excluded from this clinical&#xD;
             trial; patients with treated brain metastases stable for &gt;= 12 weeks are eligible; use&#xD;
             of corticosteroid (for patients with brain metastasis and other indications for&#xD;
             corticosteroid use) is acceptable on a low maintenance or tapering dose schedule&#xD;
&#xD;
          -  History of allergic reactions attributed to compounds of similar chemical or biologic&#xD;
             composition to ARQ 197 (tivantinib) or cetuximab&#xD;
&#xD;
          -  Concurrent life-threatening diseases: patients with diseases which with reasonable&#xD;
             certainty do not limit life expectancy to 12 months or less are eligible; assessment&#xD;
             of such concurrent illnesses should be by the principal investigator&#xD;
&#xD;
          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active&#xD;
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac&#xD;
             arrhythmia, or psychiatric illness/social situations that would limit compliance with&#xD;
             study requirements&#xD;
&#xD;
          -  Pregnant women are excluded from this study; breastfeeding should be discontinued if&#xD;
             the mother is treated with ARQ 197 (tivantinib)&#xD;
&#xD;
          -  Concurrent use of warfarin (therapeutic use) is allowed, but requires close monitoring&#xD;
             of prothrombin time (PT)/international normalized ratio (INR)&#xD;
&#xD;
          -  History of congestive heart failure defined as class II to IV per New York Heart&#xD;
             Association (NYHA) classification; active coronary artery disease (CAD), clinically&#xD;
             significant bradycardia or other uncontrolled, cardiac arrhythmia defined as &gt;= grade&#xD;
             3 according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse&#xD;
             Events (CTCAE), version 4.0, or uncontrolled hypertension; myocardial infarction&#xD;
             occurring within 6 months prior to study entry (myocardial infarction occurring &gt; 6&#xD;
             months prior to study entry is permitted)&#xD;
&#xD;
          -  Patients may not be receiving any other investigational agents&#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>Tanguy Seiwert</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Chicago Comprehensive Cancer Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mayo Clinic in Arizona</name>
      <address>
        <city>Scottsdale</city>
        <state>Arizona</state>
        <zip>85259</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>City of Hope Comprehensive Cancer Center</name>
      <address>
        <city>Duarte</city>
        <state>California</state>
        <zip>91010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>USC / Norris Comprehensive Cancer Center</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California Davis Comprehensive Cancer Center</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95817</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>City of Hope South Pasadena</name>
      <address>
        <city>South Pasadena</city>
        <state>California</state>
        <zip>91030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwestern University</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Chicago Comprehensive Cancer Center</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60637</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Decatur Memorial Hospital</name>
      <address>
        <city>Decatur</city>
        <state>Illinois</state>
        <zip>62526</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NorthShore University HealthSystem-Evanston Hospital</name>
      <address>
        <city>Evanston</city>
        <state>Illinois</state>
        <zip>60201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ingalls Memorial Hospital</name>
      <address>
        <city>Harvey</city>
        <state>Illinois</state>
        <zip>60426</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Illinois CancerCare-Peoria</name>
      <address>
        <city>Peoria</city>
        <state>Illinois</state>
        <zip>61615</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Southern Illinois University School of Medicine</name>
      <address>
        <city>Springfield</city>
        <state>Illinois</state>
        <zip>62702</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fort Wayne Medical Oncology and Hematology Inc-Parkview</name>
      <address>
        <city>Fort Wayne</city>
        <state>Indiana</state>
        <zip>46845</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Indiana University/Melvin and Bren Simon Cancer Center</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Iowa/Holden Comprehensive Cancer Center</name>
      <address>
        <city>Iowa City</city>
        <state>Iowa</state>
        <zip>52242</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Maryland/Greenebaum Cancer Center</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Michigan Comprehensive Cancer Center</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wayne State University/Karmanos Cancer Institute</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Metro Minnesota Community Oncology Research Consortium</name>
      <address>
        <city>Saint Louis Park</city>
        <state>Minnesota</state>
        <zip>55416</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington University School of Medicine</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mercy Hospital Saint Louis</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63141</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Penn State Milton S Hershey Medical Center</name>
      <address>
        <city>Hershey</city>
        <state>Pennsylvania</state>
        <zip>17033-0850</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Pittsburgh Cancer Institute (UPCI)</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>China</country>
  </removed_countries>
  <verification_date>November 2018</verification_date>
  <study_first_submitted>September 28, 2012</study_first_submitted>
  <study_first_submitted_qc>September 28, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 2, 2012</study_first_posted>
  <results_first_submitted>July 13, 2018</results_first_submitted>
  <results_first_submitted_qc>November 28, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">December 19, 2018</results_first_posted>
  <last_update_submitted>November 28, 2018</last_update_submitted>
  <last_update_submitted_qc>November 28, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">December 19, 2018</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>Head and Neck Neoplasms</mesh_term>
    <mesh_term>Squamous Cell Carcinoma of Head and Neck</mesh_term>
    <mesh_term>Recurrence</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>April 19, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/55/NCT01696955/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Arm I (Cetuximab and Tivantinib)</title>
          <description>Patients receive cetuximab 500mg/m2 IV over 60-120 minutes on days 1 and 15 and tivantinib 360mg PO BID on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.&#xD;
Cetuximab: Given IV&#xD;
Tivantinib: Given PO</description>
        </group>
        <group group_id="P2">
          <title>Arm II (Cetuximab)</title>
          <description>Patients receive cetuximab 500 mg/m2 IV over 60-120 minutes on days 1 and 15. Patients who fail (progress) on cetuximab as a single agent may then receive single agent tivantinib PO BID on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.&#xD;
Cetuximab: Given IV</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Main Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="42"/>
                <participants group_id="P2" count="39"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="40"/>
                <participants group_id="P2" count="38"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Failure on Cetuximab-Received Tivantinib</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="15"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="15">23 patients did not cross over</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Arm I (Cetuximab and Tivantinib)</title>
          <description>Patients receive cetuximab 500mg/m2 IV over 60-120 minutes on days 1 and 15 and tivantinib 360mg PO BID on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.&#xD;
Cetuximab: Given IV&#xD;
Tivantinib: Given PO</description>
        </group>
        <group group_id="B2">
          <title>Arm II (Cetuximab)</title>
          <description>Patients receive cetuximab 500mg/m2 IV over 60-120 minutes on days 1 and 15. Patients who fail (progress) on cetuximab as a single agent may then receive single agent tivantinib PO BID on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.&#xD;
Cetuximab: Given IV</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="40"/>
            <count group_id="B2" value="38"/>
            <count group_id="B3" value="78"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="60.5" lower_limit="37" upper_limit="90"/>
                    <measurement group_id="B2" value="63.6" lower_limit="35" upper_limit="87"/>
                    <measurement group_id="B3" value="62.0" lower_limit="35" upper_limit="90"/>
                  </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="6"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="34"/>
                    <measurement group_id="B2" value="32"/>
                    <measurement group_id="B3" value="66"/>
                  </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 group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="32"/>
                    <measurement group_id="B2" value="33"/>
                    <measurement group_id="B3" value="65"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="40"/>
                    <measurement group_id="B2" value="38"/>
                    <measurement group_id="B3" value="78"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Overall Response Rate</title>
        <description>Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), &gt;=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR</description>
        <time_frame>Up to 1 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Arm I (Cetuximab and Tivantinib)</title>
            <description>Patients receive cetuximab 500mg/m2 IV over 60-120 minutes on days 1 and 15 and tivantinib 360mg PO BID on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.&#xD;
Cetuximab: Given IV&#xD;
Tivantinib: Given PO</description>
          </group>
          <group group_id="O2">
            <title>Arm II (Cetuximab)</title>
            <description>Patients receive cetuximab 500mg/m2 IV over 60-120 minutes on days 1 and 15. Patients who fail (progress) on cetuximab as a single agent may then receive single agent tivantinib PO BID on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.&#xD;
Cetuximab: Given IV</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Response Rate</title>
          <description>Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), &gt;=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR</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="40"/>
                <count group_id="O2" value="38"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Complete response</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Partial response</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.99</p_value>
            <method>Fisher Exact</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>c-MET Copy Number</title>
        <description>Change in copy number from baseline to 8 weeks</description>
        <time_frame>Baseline to 8 weeks</time_frame>
        <population>Assay not performed.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm I (Cetuximab and Tivantinib)</title>
            <description>Patients receive cetuximab 500 mg/m2 IV over 60-120 minutes on days 1 and 15 and tivantinib 360 mg PO BID on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.&#xD;
Cetuximab: Given IV&#xD;
Tivantinib: Given PO</description>
          </group>
          <group group_id="O2">
            <title>Arm II (Cetuximab)</title>
            <description>Patients receive cetuximab 500 mg/m2 IV over 60-120 minutes on days 1 and 15. Patients who fail (progress) on cetuximab as a single agent may then receive single agent tivantinib PO BID on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.&#xD;
Cetuximab: Given IV</description>
          </group>
        </group_list>
        <measure>
          <title>c-MET Copy Number</title>
          <description>Change in copy number from baseline to 8 weeks</description>
          <population>Assay not performed.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>c-MET Expression</title>
        <description>Change in c-MET expression from baseline to 8 weeks</description>
        <time_frame>Baseline to 8 weeks</time_frame>
        <population>Assay not performed.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm I (Cetuximab and Tivantinib)</title>
            <description>Patients receive cetuximab 500mg/m2 IV over 60-120 minutes on days 1 and 15 and tivantinib 360mg PO BID on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.&#xD;
Cetuximab: Given IV&#xD;
Tivantinib: Given PO</description>
          </group>
          <group group_id="O2">
            <title>Arm II (Cetuximab)</title>
            <description>Patients receive cetuximab 500mg/m2 IV over 60-120 minutes on days 1 and 15. Patients who fail (progress) on cetuximab as a single agent may then receive single agent tivantinib PO BID on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.&#xD;
Cetuximab: Given IV</description>
          </group>
        </group_list>
        <measure>
          <title>c-MET Expression</title>
          <description>Change in c-MET expression from baseline to 8 weeks</description>
          <population>Assay not performed.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Tumor Burden</title>
        <description>Early change in tumor burden measured using the sum of longest diameters of target lesions, expressed as percent change from baseline.</description>
        <time_frame>Baseline to 8 weeks</time_frame>
        <population>Patients with baseline and 8 week measurements available</population>
        <group_list>
          <group group_id="O1">
            <title>Arm I (Cetuximab and Tivantinib)</title>
            <description>Patients receive cetuximab 500 mg/m2 IV over 60-120 minutes on days 1 and 15 and tivantinib 360mg PO BID on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.&#xD;
Cetuximab: Given IV&#xD;
Tivantinib: Given PO</description>
          </group>
          <group group_id="O2">
            <title>Arm II (Cetuximab)</title>
            <description>Patients receive cetuximab 500 mg/m2 IV over 60-120 minutes on days 1 and 15. Patients who fail (progress) on cetuximab as a single agent may then receive single agent tivantinib PO BID on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.&#xD;
Cetuximab: Given IV</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Tumor Burden</title>
          <description>Early change in tumor burden measured using the sum of longest diameters of target lesions, expressed as percent change from baseline.</description>
          <population>Patients with baseline and 8 week measurements available</population>
          <units>percent change</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="32"/>
                <count group_id="O2" value="31"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15.0" spread="6.1"/>
                    <measurement group_id="O2" value="9.0" spread="5.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.47</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival</title>
        <description>Time from randomization until death or date last known alive</description>
        <time_frame>Up to 5 years</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Arm I (Cetuximab and Tivantinib)</title>
            <description>Patients receive cetuximab IV over 60-120 minutes on days 1 and 15 and tivantinib PO BID on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.&#xD;
Cetuximab: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Tivantinib: Given PO</description>
          </group>
          <group group_id="O2">
            <title>Arm II (Cetuximab)</title>
            <description>Patients receive cetuximab IV over 60-120 minutes on days 1 and 15. Patients who fail cetuximab as a single agent may receive single agent tivantinib PO BID on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.&#xD;
Cetuximab: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival</title>
          <description>Time from randomization until death or date last known alive</description>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="40"/>
                <count group_id="O2" value="38"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.4" lower_limit="4.7" upper_limit="10.3"/>
                    <measurement group_id="O2" value="8.6" lower_limit="5.7" upper_limit="11.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.99</p_value>
            <method>Log Rank</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression-free Survival</title>
        <description>Time from randomization until disease progression/death from any cause or date last know progression-free</description>
        <time_frame>Up to 3 years</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Arm I (Cetuximab and Tivantinib)</title>
            <description>Patients receive cetuximab 500mg/m2 IV over 60-120 minutes on days 1 and 15 and tivantinib 360mg PO BID on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.&#xD;
Cetuximab: Given IV&#xD;
Tivantinib: Given PO</description>
          </group>
          <group group_id="O2">
            <title>Arm II (Cetuximab)</title>
            <description>Patients receive cetuximab 500mg/m2 IV over 60-120 minutes on days 1 and 15. Patients who fail (progress) on cetuximab as a single agent may then receive single agent tivantinib PO BID on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.&#xD;
Cetuximab: Given IV</description>
          </group>
        </group_list>
        <measure>
          <title>Progression-free Survival</title>
          <description>Time from randomization until disease progression/death from any cause or date last know progression-free</description>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="40"/>
                <count group_id="O2" value="38"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.5" lower_limit="1.8" upper_limit="3.9"/>
                    <measurement group_id="O2" value="3.5" lower_limit="2.0" upper_limit="3.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.58</p_value>
            <method>Log Rank</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Response Rate of Single-agent Tivantinib After Failure of Cetuximab</title>
        <description>Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), &gt;=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR</description>
        <time_frame>Up to 1 year</time_frame>
        <population>This outcome pertains only to Tivantinib after Cetuximab failure and therefore Arm 1 contains 0 analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm I (Cetuximab and Tivantinib)</title>
            <description>Patients receive cetuximab 500 mg/m2 IV over 60-120 minutes on days 1 and 15 and tivantinib 360mg PO BID on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.&#xD;
Cetuximab: Given IV&#xD;
Tivantinib: Given PO</description>
          </group>
          <group group_id="O2">
            <title>Tivantinib After Cetuximab Failure</title>
            <description>ARQ 197 (tivantinib) 360mg PO BID on days 1-28.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Response Rate of Single-agent Tivantinib After Failure of Cetuximab</title>
          <description>Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), &gt;=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR</description>
          <population>This outcome pertains only to Tivantinib after Cetuximab failure and therefore Arm 1 contains 0 analyzed.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Number of Participants With Adverse Events While on Single-agent Tivantinib After Failure of Cetuximab</title>
        <description>Non-serious adverse events, CTCAE (4.0)</description>
        <time_frame>Up to 3 years</time_frame>
        <population>This outcome pertains only to Tivantinib after Cetuximab Failure and therefore Arm 1 contains 0 analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm I (Cetuximab and Tivantinib)</title>
            <description>Patients receive cetuximab IV over 60-120 minutes on days 1 and 15 and tivantinib PO BID on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.&#xD;
Cetuximab: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Tivantinib: Given PO</description>
          </group>
          <group group_id="O2">
            <title>Tivantinib After Cetuximab Failure</title>
            <description>ARQ 197 (tivantinib) 360mg PO BID on days 1-28.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Adverse Events While on Single-agent Tivantinib After Failure of Cetuximab</title>
          <description>Non-serious adverse events, CTCAE (4.0)</description>
          <population>This outcome pertains only to Tivantinib after Cetuximab Failure and therefore Arm 1 contains 0 analyzed.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Number of Patients With Serious Adverse Events While on Single-agent Tivantinib After Failure of Cetuximab</title>
        <description>CTCAE (4.0)</description>
        <time_frame>3 years</time_frame>
        <population>This outcome pertains only to Tivantinib after Cetuximab Failure and therefore Arm 1 contains 0 analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm I (Cetuximab and Tivantinib)</title>
            <description>Patients receive cetuximab IV over 60-120 minutes on days 1 and 15 and tivantinib PO BID on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.&#xD;
Cetuximab: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Tivantinib: Given PO</description>
          </group>
          <group group_id="O2">
            <title>Tivantinib After Cetuximab Failure</title>
            <description>ARQ 197 (tivantinib) 360mg PO BID on days 1-28.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Patients With Serious Adverse Events While on Single-agent Tivantinib After Failure of Cetuximab</title>
          <description>CTCAE (4.0)</description>
          <population>This outcome pertains only to Tivantinib after Cetuximab Failure and therefore Arm 1 contains 0 analyzed.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>3 years</time_frame>
      <desc>Note: Adverse events reported in Arm II were prior to any crossover to combination therapy.</desc>
      <group_list>
        <group group_id="E1">
          <title>Arm I (Cetuximab and Tivantinib)</title>
          <description>Patients receive cetuximab 500mg/m2 IV over 60-120 minutes on days 1 and 15 and tivantinib 360mg PO BID on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.&#xD;
Cetuximab: Given IV&#xD;
Tivantinib: Given PO</description>
        </group>
        <group group_id="E2">
          <title>Arm II (Cetuximab)</title>
          <description>Patients receive cetuximab 500mg/m2 IV over 60-120 minutes on days 1 and 15. Patients who fail (progress) on cetuximab as a single agent may then receive single agent tivantinib PO BID on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.&#xD;
Cetuximab: Given IV</description>
        </group>
        <group group_id="E3">
          <title>Single-agent Tivantinib After Failure of Cetuximab</title>
          <description>Patients receive cetuximab 500mg/m2 IV over 60-120 minutes on days 1 and 15.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>CTCAE (4.0)</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="36" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="35" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="19" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="18" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Febrile neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Sinus bradycardia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Death NOS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Infusion related reaction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Edema face</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Hepatic failure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Skin infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Infections - Other</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Tracheal hemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alkaline phosphatase increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Cardiac arrest</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>White blood cell decreased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Hypercalcemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Hypomagnesemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Hypophosphatemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="0" 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>Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Ataxia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Nervous system disorders - Other, specify</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Confusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Laryngeal edema</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Pneumonitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Pneumothorax</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Respiratory, thoracic and mediastinal disorders - Other, specify</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash acneiform</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Surgical and medical procedures - Other, specify</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>CTCAE (4.0)</default_vocab>
        <default_assessment>Non-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="38" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="35" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="9" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Sinus bradycardia</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Pericardial effusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Sinus tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Eye disorders - Other, specify</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Flu like symptoms</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Oral pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Edema limbs</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="21" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="17" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Infusion related reaction</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Edema face</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Pharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Dermatitis radiation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Alkaline phosphatase increased</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>White blood cell decreased</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Creatinine increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Hyperkalemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Hypoalbuminemia</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Hypocalcemia</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Hypomagnesemia</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Hypophosphatemia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Hypercalcemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Metabolism and nutrition disorders-Other</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Musculoskeletal and connective tissue disorder - Other</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Peripheral sensory neuropathy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Hallucinations</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Productive cough</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Rash acneiform</sub_title>
                <counts group_id="E1" subjects_affected="20" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="19" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Rash/dermatitis</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Skin and subcutaneous tissue disorders - Other, specify</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Erythema multiforme</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Palmar-plantar erythrodysesthesia syndrome</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Papulopustular rash</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="38"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Theodore Karrison</name_or_title>
      <organization>University of Chicago</organization>
      <phone>773-702-9326</phone>
      <email>tkarrison@health.bsd.uchicago.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/NCT01696955
org study id: NCI-2012-01640
secondary id: NCI-2012-01640
secondary id: 12-1359
secondary id: 478834
secondary id: 9165
secondary id: 9165
secondary id: N01CM00038
secondary id: N01CM00071
secondary id: N01CM00099
secondary id: P30CA014599
nct id: NCT01696955
lead sponsor: 
has dmc: No
This randomized phase II trial studies how well cetuximab with or without tivantinib works in
      treating patients with head and neck cancer that has come back (recurrent), has spread to
      other places in the body (metastatic), or cannot be removed by surgery. Monoclonal
      antibodies, such as cetuximab, may interfere with the ability of tumor cells to grow and
      spread. Tivantinib may stop the growth of tumor cells by blocking some of the enzymes needed
      for cell growth. It is not yet known whether cetuximab is more effective with or without
      tivantinib in treating patients with head and neck cancer.
PRIMARY OBJECTIVES:

      I. Response rate (comparing the cetuximab/ARQ 197 [tivantinib] combination with cetuximab
      single agent activity).

      SECONDARY OBJECTIVES:

      I. Continuous tumor shrinkage. II. Progression-free survival (PFS). III. Overall survival
      (OS). IV. Objectives I, II, and III above, as well as response rates, will be assessed and
      compared between treatment arms in the subgroup of patients with high mesenchymal epithelial
      transition factor (c-MET) expression, and/or high c-MET copy number.

      V. Single agent activity for ARQ 197 (tivantinib) in patients who have failed cetuximab.

      OUTLINE: Patients are randomized to 1 of 2 treatment arms.

      ARM I: Patients receive cetuximab intravenously (IV) over 60-120 minutes on days 1 and 15 and
      tivantinib orally (PO) twice daily (BID) on days 1-28. Courses repeat every 4 weeks in the
      absence of disease progression or unacceptable toxicity.

      ARM II: Patients receive cetuximab IV over 60-120 minutes on days 1 and 15. Patients who fail
      cetuximab as a single agent may receive single agent tivantinib PO BID on days 1-28. Courses
      repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up for 5 years.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Overall Response Rate
time frame: Up to 1 year
description: Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
measure: c-MET Copy Number
time frame: Baseline to 8 weeks
description: Change in copy number from baseline to 8 weeks
measure: c-MET Expression
time frame: Baseline to 8 weeks
description: Change in c-MET expression from baseline to 8 weeks
measure: Change in Tumor Burden
time frame: Baseline to 8 weeks
description: Early change in tumor burden measured using the sum of longest diameters of target lesions, expressed as percent change from baseline.
measure: Overall Survival
time frame: Up to 5 years
description: Time from randomization until death or date last known alive
measure: Progression-free Survival
time frame: Up to 3 years
description: Time from randomization until disease progression/death from any cause or date last know progression-free
measure: Overall Response Rate of Single-agent Tivantinib After Failure of Cetuximab
time frame: Up to 1 year
description: Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
measure: Number of Participants With Adverse Events While on Single-agent Tivantinib After Failure of Cetuximab
time frame: Up to 3 years
description: Non-serious adverse events, CTCAE (4.0)
measure: Number of Patients With Serious Adverse Events While on Single-agent Tivantinib After Failure of Cetuximab
time frame: 3 years
description: CTCAE (4.0)
arm group label: Arm I (cetuximab and tivantinib)
arm group type: Experimental
description: Patients receive cetuximab IV over 60-120 minutes on days 1 and 15 and tivantinib PO BID on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
arm group label: Arm II (cetuximab)
arm group type: Experimental
description: Patients receive cetuximab IV over 60-120 minutes on days 1 and 15. Patients who fail cetuximab as a single agent may receive single agent tivantinib PO BID on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
intervention type: Biological
intervention name: Cetuximab
description: Given IV
arm group label: Arm I (cetuximab and tivantinib)
arm group label: Arm II (cetuximab)
intervention type: Other
intervention name: Laboratory Biomarker Analysis
description: Correlative studies
arm group label: Arm I (cetuximab and tivantinib)
arm group label: Arm II (cetuximab)
intervention type: Drug
intervention name: Tivantinib
description: Given PO
arm group label: Arm I (cetuximab and tivantinib)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Tanguy Seiwert
role: Principal Investigator
affiliation: University of Chicago Comprehensive Cancer Center
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country: United States
country: China
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Head and Neck Neoplasms
mesh term: Squamous Cell Carcinoma of Head and Neck
mesh term: Recurrence
mesh term: Cetuximab
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 