<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/NCT01682031</url>
  </required_header>
  <id_info>
    <org_study_id>I 107807</org_study_id>
    <secondary_id>NCI-2009-01503</secondary_id>
    <nct_id>NCT01682031</nct_id>
    <nct_alias>NCT00935038</nct_alias>
  </id_info>
  <brief_title>Selenomethionine in Reducing Mucositis in Patients With Locally Advanced Head and Neck Cancer Who Are Receiving Cisplatin and Radiation Therapy</brief_title>
  <official_title>Randomized, Double-Blind, Placebo-Controlled, Multi-Center, Phase II Trial of Selenomethionine as a Modulator of Efficacy and Toxicity of Chemoradiation in Locally-Advanced Squamous Cell Carcinoma of the Head and Neck</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Roswell Park Cancer Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Roswell Park Cancer Institute</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This randomized phase II trial is studying how well selenomethionine (SLM) works in reducing&#xD;
      mucositis in patients with locally advanced head and neck cancer who are receiving cisplatin&#xD;
      and radiation therapy. SLM may help prevent or reduce mucositis, or mouth sores, in patients&#xD;
      receiving chemotherapy and radiation therapy. It is not yet known whether SLM is more&#xD;
      effective than a placebo in reducing mucositis&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To assess whether SLM reduces the incidence of grade 3 or 4 mucositis in head and neck&#xD;
      squamous cell carcinoma (HNSCC) patients treated with concurrent chemoradiation (CRT) over 7&#xD;
      weeks.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To assess the impact of SLM on tumor complete response rate, relapse-free survival,&#xD;
      overall survival and quality of life.&#xD;
&#xD;
      II. To assess whether SLM reduces the incidence and severity of treatment-related toxicities&#xD;
      including xerostomia, renal impairment and myelosuppression.&#xD;
&#xD;
      III. To assess whether SLM improves chemoradiation dose delivery. IV. To determine safety of&#xD;
      SLM at this dose. V. In New Zealand (NZ) patients only, to assess the impact of SLM on plasma&#xD;
      free cisplatin and plasma selenium pharmacokinetics (PK) and on pharmacodynamic (PD) markers&#xD;
      of biological activity of selenium.&#xD;
&#xD;
      OUTLINE: Patients are randomized to 1 of 2 treatment arms.&#xD;
&#xD;
      ARM I: Patients receive placebo orally (PO) twice daily in week 1 and then once daily in&#xD;
      weeks 2-11. Patients also receive cisplatin intravenously (IV) over 3 hours once in weeks 2,&#xD;
      5, and 8 and undergo radiotherapy 5 days a week in weeks 2-8.&#xD;
&#xD;
      ARM II: Patients receive selenomethionine PO twice daily in week 1 and then once daily in&#xD;
      weeks 2-11. Patients also receive cisplatin and undergo radiotherapy as in arm I.&#xD;
&#xD;
      After completion of study treatment, patients are followed up periodically.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Due to a lack of funding&#xD;
  </why_stopped>
  <start_date>June 2009</start_date>
  <completion_date type="Actual">June 2012</completion_date>
  <primary_completion_date type="Actual">April 2012</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>Supportive Care</primary_purpose>
    <masking>Double</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of &gt;= Grade 3 Mucositis</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Will be compared as difference in proportions with 95% confidence intervals.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Tumor Complete Response Rate</measure>
    <time_frame>Up to 5 years post-treatment</time_frame>
    <description>Will be compared as difference in proportions with 95% confidence intervals. Disease will be measured according to the Response Evaluation Criteria in Solid Tumors (RECIST).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Relapse-free Survival (RFS)</measure>
    <time_frame>At 1 year</time_frame>
    <description>Assessed by Kaplan-Meier RFS curves and the proportion with an event at 1 year for RFS will be compared simultaneously to obtain more global sensitivity to differences in time-to-event.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>Up to 5 years post-treatment</time_frame>
    <description>Estimated using the Kaplan-Meier method. Log-rank tests will be used for the comparison of survival distributions among study groups. Continuous endpoints will be summarized using means, standard deviations and percentiles.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of Life</measure>
    <time_frame>Up to 1 year post-treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Grade 3 or 4 Treatment-related Toxicities, Including Xerostomia</measure>
    <time_frame>Up to 5 years post-treatment</time_frame>
    <description>Will be compared as difference in proportions with 95% confidence intervals.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CRT Dose Delivery</measure>
    <time_frame>Up to 8 weeks</time_frame>
    <description>This characteristic will be included in Cox models.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma Cisplatin and Selenium PK and PD Markers (NZ Only)</measure>
    <time_frame>Up to 3 months post-treatment</time_frame>
    <description>Descriptive statistics will be used to describe the mean plasma cisplatin and selenium at each time point. Repeated measures analysis of variance will be used to evaluate the changes in plasma cisplatin and selenium over time. Analysis of pharmacodynamic markers will be conducted using statistical methods appropriate for within-patient sequential analyses, such as repeated measures analysis of variance.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">18</enrollment>
  <condition>Chemotherapeutic Agent Toxicity</condition>
  <condition>Mucositis</condition>
  <condition>Radiation Toxicity</condition>
  <condition>Stage III Squamous Cell Carcinoma of the Hypopharynx</condition>
  <condition>Stage III Squamous Cell Carcinoma of the Larynx</condition>
  <condition>Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity</condition>
  <condition>Stage III Squamous Cell Carcinoma of the Nasopharynx</condition>
  <condition>Stage III Squamous Cell Carcinoma of the Oropharynx</condition>
  <condition>Stage III Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity</condition>
  <condition>Stage IV Squamous Cell Carcinoma of the Hypopharynx</condition>
  <condition>Stage IV Squamous Cell Carcinoma of the Larynx</condition>
  <condition>Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity</condition>
  <condition>Stage IV Squamous Cell Carcinoma of the Nasopharynx</condition>
  <condition>Stage IV Squamous Cell Carcinoma of the Oropharynx</condition>
  <condition>Stage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity</condition>
  <condition>Xerostomia</condition>
  <arm_group>
    <arm_group_label>Arm I (placebo, cisplatin, and radiotherapy)</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Patients receive placebo PO twice daily in week 1 and then once daily in weeks 2-11. Patients also receive cisplatin IV over 3 hours once in weeks 2, 5, and 8 and undergo radiotherapy 5 days a week in weeks 2-8.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm II (selenomethionine, cisplatin, and radiotherapy)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive selenomethionine PO twice daily in week 1 and then once daily in weeks 2-11. Patients also receive cisplatin and undergo radiotherapy as in arm I.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>selenomethionine</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Arm II (selenomethionine, cisplatin, and radiotherapy)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>placebo</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Arm I (placebo, cisplatin, and radiotherapy)</arm_group_label>
    <other_name>PLCB</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>cisplatin</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Arm I (placebo, cisplatin, and radiotherapy)</arm_group_label>
    <arm_group_label>Arm II (selenomethionine, cisplatin, and radiotherapy)</arm_group_label>
    <other_name>CACP</other_name>
    <other_name>CDDP</other_name>
    <other_name>CPDD</other_name>
    <other_name>DDP</other_name>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>radiation therapy</intervention_name>
    <description>Undergo radiotherapy</description>
    <arm_group_label>Arm I (placebo, cisplatin, and radiotherapy)</arm_group_label>
    <arm_group_label>Arm II (selenomethionine, cisplatin, and radiotherapy)</arm_group_label>
    <other_name>irradiation</other_name>
    <other_name>radiotherapy</other_name>
    <other_name>therapy, radiation</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>quality-of-life assessment</intervention_name>
    <description>Ancillary studies</description>
    <arm_group_label>Arm I (placebo, cisplatin, and radiotherapy)</arm_group_label>
    <arm_group_label>Arm II (selenomethionine, cisplatin, and radiotherapy)</arm_group_label>
    <other_name>quality of life assessment</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Biopsy-proven locally-advanced HNSCC, including those with cancers of the oral cavity,&#xD;
             oropharynx, hypopharynx, larynx, nasopharynx or paranasal sinuses&#xD;
&#xD;
          -  Stage III, IVa or IVb disease&#xD;
&#xD;
          -  No prior definitive surgery for present diagnosis&#xD;
&#xD;
          -  Appropriate candidate for concurrent cisplatin and radiation as definitive treatment;&#xD;
             patients who receive induction chemotherapy as part of a definitive treatment program&#xD;
             that will include concurrent CRT are eligible for this study&#xD;
&#xD;
          -  Hemoglobin &gt;= 10 g/dL (100 g/l)&#xD;
&#xD;
          -  Absolute neutrophil count &gt;= 2,000 cells/mm^3 (2 x 10^9/l)&#xD;
&#xD;
          -  Platelets &gt;= 100,000 cells/mm^3 (100 x 10^9/l)&#xD;
&#xD;
          -  Serum creatinine =&lt; 1.5 mg/dL (133 umol/l) or calculated creatinine clearance &gt;= 50&#xD;
             ml/min using the Cockcroft-Gault formula&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-2&#xD;
&#xD;
          -  Able to give written informed consent&#xD;
&#xD;
          -  Be willing and able to comply with study procedures&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Non-regional metastatic disease (stage IVc)&#xD;
&#xD;
          -  Previous malignancy within the last 5 years except for adequately treated basal or&#xD;
             squamous cell carcinoma of the skin or cervical intra-epithelial neoplasia&#xD;
&#xD;
          -  Prior chemotherapy or radiotherapy for HNSCC, or any prior radiotherapy that would&#xD;
             compromise delivery of a radical dose to the HNSCC&#xD;
&#xD;
          -  Known to be positive for hepatitis C or human immunodeficiency virus (HIV)&#xD;
&#xD;
          -  Unable to tolerate oral medication (unless a feeding tube is in place)&#xD;
&#xD;
          -  History of hypersensitivity to platinum drugs&#xD;
&#xD;
          -  Symptomatic peripheral neuropathy &gt;= National Cancer Institute (NCI)-Common&#xD;
             Terminology Criteria for Adverse Events (CTCAE) grade II&#xD;
&#xD;
          -  Pregnant, lactating or unwilling to use adequate contraception&#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&#xD;
&#xD;
          -  Planned use of amifostine for prophylaxis against radiation-induced xerostomia&#xD;
&#xD;
          -  Patients taking selenium supplements in excess of 100 ug/day&#xD;
&#xD;
          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active&#xD;
             infection, symptomatic congestive heart failure, unstable angina pectoris, clinically&#xD;
             significant cardiac arrhythmia, or psychiatric illness/social situations that would&#xD;
             limit compliance with study requirements&#xD;
&#xD;
          -  Evidence of any other significant medical disorder or laboratory finding that in the&#xD;
             opinion of the Investigator compromises the subject's safety during the study&#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>Anurag Singh</last_name>
    <role>Principal Investigator</role>
    <affiliation>Roswell Park Cancer Institute</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Roswell Park Cancer Institute</name>
      <address>
        <city>Buffalo</city>
        <state>New York</state>
        <zip>14263</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Waikato Hospital</name>
      <address>
        <city>Hamilton</city>
        <zip>3204</zip>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>New Zealand</country>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2014</verification_date>
  <study_first_submitted>September 5, 2012</study_first_submitted>
  <study_first_submitted_qc>September 7, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 10, 2012</study_first_posted>
  <results_first_submitted>June 26, 2014</results_first_submitted>
  <results_first_submitted_qc>August 8, 2014</results_first_submitted_qc>
  <results_first_posted type="Estimate">August 22, 2014</results_first_posted>
  <last_update_submitted>August 8, 2014</last_update_submitted>
  <last_update_submitted_qc>August 8, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 22, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Carcinoma, Squamous Cell</mesh_term>
    <mesh_term>Laryngeal Neoplasms</mesh_term>
    <mesh_term>Oropharyngeal Neoplasms</mesh_term>
    <mesh_term>Squamous Cell Carcinoma of Head and Neck</mesh_term>
    <mesh_term>Nasopharyngeal Carcinoma</mesh_term>
    <mesh_term>Paranasal Sinus Neoplasms</mesh_term>
    <mesh_term>Mucositis</mesh_term>
    <mesh_term>Xerostomia</mesh_term>
    <mesh_term>Laryngeal Diseases</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Selenium</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Arm I (Placebo, Cisplatin, and Radiotherapy)</title>
          <description>Patients receive placebo PO twice daily in week 1 and then once daily in weeks 2-11. Patients also receive cisplatin IV over 3 hours once in weeks 2, 5, and 8 and undergo radiotherapy 5 days a week in weeks 2-8.&#xD;
placebo: Given PO&#xD;
cisplatin: Given IV&#xD;
radiation therapy: Undergo radiotherapy&#xD;
quality-of-life assessment: Ancillary studies</description>
        </group>
        <group group_id="P2">
          <title>Arm II (Selenomethionine, Cisplatin, and Radiotherapy)</title>
          <description>Patients receive selenomethionine PO twice daily in week 1 and then once daily in weeks 2-11. Patients also receive cisplatin and undergo radiotherapy as in arm I.&#xD;
selenomethionine: Given PO&#xD;
cisplatin: Given IV&#xD;
radiation therapy: Undergo radiotherapy&#xD;
quality-of-life assessment: Ancillary studies</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="10"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>MRI results indicate increased nodul</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Patient could not swallow tablets</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Patient stopped selenium on his own</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Arm I (Placebo, Cisplatin, and Radiotherapy)</title>
          <description>Patients receive placebo PO twice daily in week 1 and then once daily in weeks 2-11. Patients also receive cisplatin IV over 3 hours once in weeks 2, 5, and 8 and undergo radiotherapy 5 days a week in weeks 2-8.&#xD;
placebo: Given PO&#xD;
cisplatin: Given IV&#xD;
radiation therapy: Undergo radiotherapy&#xD;
quality-of-life assessment: Ancillary studies</description>
        </group>
        <group group_id="B2">
          <title>Arm II (Selenomethionine, Cisplatin, and Radiotherapy)</title>
          <description>Patients receive selenomethionine PO twice daily in week 1 and then once daily in weeks 2-11. Patients also receive cisplatin and undergo radiotherapy as in arm I.&#xD;
selenomethionine: Given PO&#xD;
cisplatin: Given IV&#xD;
radiation therapy: Undergo radiotherapy&#xD;
quality-of-life assessment: Ancillary studies</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="8"/>
            <count group_id="B2" value="10"/>
            <count group_id="B3" value="18"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="56.6" spread="6.6"/>
                    <measurement group_id="B2" value="57.4" spread="8.2"/>
                    <measurement group_id="B3" value="57.1" spread="7.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</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>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="16"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </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="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Incidence of &gt;= Grade 3 Mucositis</title>
        <description>Will be compared as difference in proportions with 95% confidence intervals.</description>
        <time_frame>Up to 5 years</time_frame>
        <population>Due to the study's early termination and inadequate number of patients, no patients were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm I (Placebo, Cisplatin, and Radiotherapy)</title>
            <description>Patients receive placebo PO twice daily in week 1 and then once daily in weeks 2-11. Patients also receive cisplatin IV over 3 hours once in weeks 2, 5, and 8 and undergo radiotherapy 5 days a week in weeks 2-8.&#xD;
placebo: Given PO&#xD;
cisplatin: Given IV&#xD;
radiation therapy: Undergo radiotherapy&#xD;
quality-of-life assessment: Ancillary studies</description>
          </group>
          <group group_id="O2">
            <title>Arm II (Selenomethionine, Cisplatin, and Radiotherapy)</title>
            <description>Patients receive selenomethionine PO twice daily in week 1 and then once daily in weeks 2-11. Patients also receive cisplatin and undergo radiotherapy as in arm I.&#xD;
selenomethionine: Given PO&#xD;
cisplatin: Given IV&#xD;
radiation therapy: Undergo radiotherapy&#xD;
quality-of-life assessment: Ancillary studies</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence of &gt;= Grade 3 Mucositis</title>
          <description>Will be compared as difference in proportions with 95% confidence intervals.</description>
          <population>Due to the study's early termination and inadequate number of patients, no patients were analyzed.</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>Tumor Complete Response Rate</title>
        <description>Will be compared as difference in proportions with 95% confidence intervals. Disease will be measured according to the Response Evaluation Criteria in Solid Tumors (RECIST).</description>
        <time_frame>Up to 5 years post-treatment</time_frame>
        <population>Due to the study's early termination and inadequate number of patients, no patients were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm I (Placebo, Cisplatin, and Radiotherapy)</title>
            <description>Patients receive placebo PO twice daily in week 1 and then once daily in weeks 2-11. Patients also receive cisplatin IV over 3 hours once in weeks 2, 5, and 8 and undergo radiotherapy 5 days a week in weeks 2-8.&#xD;
placebo: Given PO&#xD;
cisplatin: Given IV&#xD;
radiation therapy: Undergo radiotherapy&#xD;
quality-of-life assessment: Ancillary studies</description>
          </group>
          <group group_id="O2">
            <title>Arm II (Selenomethionine, Cisplatin, and Radiotherapy)</title>
            <description>Patients receive selenomethionine PO twice daily in week 1 and then once daily in weeks 2-11. Patients also receive cisplatin and undergo radiotherapy as in arm I.&#xD;
selenomethionine: Given PO&#xD;
cisplatin: Given IV&#xD;
radiation therapy: Undergo radiotherapy&#xD;
quality-of-life assessment: Ancillary studies</description>
          </group>
        </group_list>
        <measure>
          <title>Tumor Complete Response Rate</title>
          <description>Will be compared as difference in proportions with 95% confidence intervals. Disease will be measured according to the Response Evaluation Criteria in Solid Tumors (RECIST).</description>
          <population>Due to the study's early termination and inadequate number of patients, no patients were analyzed.</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>Relapse-free Survival (RFS)</title>
        <description>Assessed by Kaplan-Meier RFS curves and the proportion with an event at 1 year for RFS will be compared simultaneously to obtain more global sensitivity to differences in time-to-event.</description>
        <time_frame>At 1 year</time_frame>
        <population>Due to the study's early termination and inadequate number of patients, no patients were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm I (Placebo, Cisplatin, and Radiotherapy)</title>
            <description>Patients receive placebo PO twice daily in week 1 and then once daily in weeks 2-11. Patients also receive cisplatin IV over 3 hours once in weeks 2, 5, and 8 and undergo radiotherapy 5 days a week in weeks 2-8.&#xD;
placebo: Given PO&#xD;
cisplatin: Given IV&#xD;
radiation therapy: Undergo radiotherapy&#xD;
quality-of-life assessment: Ancillary studies</description>
          </group>
          <group group_id="O2">
            <title>Arm II (Selenomethionine, Cisplatin, and Radiotherapy)</title>
            <description>Patients receive selenomethionine PO twice daily in week 1 and then once daily in weeks 2-11. Patients also receive cisplatin and undergo radiotherapy as in arm I.&#xD;
selenomethionine: Given PO&#xD;
cisplatin: Given IV&#xD;
radiation therapy: Undergo radiotherapy&#xD;
quality-of-life assessment: Ancillary studies</description>
          </group>
        </group_list>
        <measure>
          <title>Relapse-free Survival (RFS)</title>
          <description>Assessed by Kaplan-Meier RFS curves and the proportion with an event at 1 year for RFS will be compared simultaneously to obtain more global sensitivity to differences in time-to-event.</description>
          <population>Due to the study's early termination and inadequate number of patients, no patients were analyzed.</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>Overall Survival</title>
        <description>Estimated using the Kaplan-Meier method. Log-rank tests will be used for the comparison of survival distributions among study groups. Continuous endpoints will be summarized using means, standard deviations and percentiles.</description>
        <time_frame>Up to 5 years post-treatment</time_frame>
        <population>Due to the study's early termination and inadequate number of patients, no patients were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm I (Placebo, Cisplatin, and Radiotherapy)</title>
            <description>Patients receive placebo PO twice daily in week 1 and then once daily in weeks 2-11. Patients also receive cisplatin IV over 3 hours once in weeks 2, 5, and 8 and undergo radiotherapy 5 days a week in weeks 2-8.&#xD;
placebo: Given PO&#xD;
cisplatin: Given IV&#xD;
radiation therapy: Undergo radiotherapy&#xD;
quality-of-life assessment: Ancillary studies</description>
          </group>
          <group group_id="O2">
            <title>Arm II (Selenomethionine, Cisplatin, and Radiotherapy)</title>
            <description>Patients receive selenomethionine PO twice daily in week 1 and then once daily in weeks 2-11. Patients also receive cisplatin and undergo radiotherapy as in arm I.&#xD;
selenomethionine: Given PO&#xD;
cisplatin: Given IV&#xD;
radiation therapy: Undergo radiotherapy&#xD;
quality-of-life assessment: Ancillary studies</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival</title>
          <description>Estimated using the Kaplan-Meier method. Log-rank tests will be used for the comparison of survival distributions among study groups. Continuous endpoints will be summarized using means, standard deviations and percentiles.</description>
          <population>Due to the study's early termination and inadequate number of patients, no patients were analyzed.</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>Quality of Life</title>
        <time_frame>Up to 1 year post-treatment</time_frame>
        <population>Due to the study's early termination and inadequate number of patients, no patients were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm I (Placebo, Cisplatin, and Radiotherapy)</title>
            <description>Patients receive placebo PO twice daily in week 1 and then once daily in weeks 2-11. Patients also receive cisplatin IV over 3 hours once in weeks 2, 5, and 8 and undergo radiotherapy 5 days a week in weeks 2-8.&#xD;
placebo: Given PO&#xD;
cisplatin: Given IV&#xD;
radiation therapy: Undergo radiotherapy&#xD;
quality-of-life assessment: Ancillary studies</description>
          </group>
          <group group_id="O2">
            <title>Arm II (Selenomethionine, Cisplatin, and Radiotherapy)</title>
            <description>Patients receive selenomethionine PO twice daily in week 1 and then once daily in weeks 2-11. Patients also receive cisplatin and undergo radiotherapy as in arm I.&#xD;
selenomethionine: Given PO&#xD;
cisplatin: Given IV&#xD;
radiation therapy: Undergo radiotherapy&#xD;
quality-of-life assessment: Ancillary studies</description>
          </group>
        </group_list>
        <measure>
          <title>Quality of Life</title>
          <population>Due to the study's early termination and inadequate number of patients, no patients were analyzed.</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>Incidence of Grade 3 or 4 Treatment-related Toxicities, Including Xerostomia</title>
        <description>Will be compared as difference in proportions with 95% confidence intervals.</description>
        <time_frame>Up to 5 years post-treatment</time_frame>
        <population>All treated and eligible patients</population>
        <group_list>
          <group group_id="O1">
            <title>Arm I (Placebo, Cisplatin, and Radiotherapy)</title>
            <description>Patients receive placebo PO twice daily in week 1 and then once daily in weeks 2-11. Patients also receive cisplatin IV over 3 hours once in weeks 2, 5, and 8 and undergo radiotherapy 5 days a week in weeks 2-8.&#xD;
placebo: Given PO&#xD;
cisplatin: Given IV&#xD;
radiation therapy: Undergo radiotherapy&#xD;
quality-of-life assessment: Ancillary studies</description>
          </group>
          <group group_id="O2">
            <title>Arm II (Selenomethionine, Cisplatin, and Radiotherapy)</title>
            <description>Patients receive selenomethionine PO twice daily in week 1 and then once daily in weeks 2-11. Patients also receive cisplatin and undergo radiotherapy as in arm I.&#xD;
selenomethionine: Given PO&#xD;
cisplatin: Given IV&#xD;
radiation therapy: Undergo radiotherapy&#xD;
quality-of-life assessment: Ancillary studies</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence of Grade 3 or 4 Treatment-related Toxicities, Including Xerostomia</title>
          <description>Will be compared as difference in proportions with 95% confidence intervals.</description>
          <population>All treated and eligible patients</population>
          <units>number of xerostomia events</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>CRT Dose Delivery</title>
        <description>This characteristic will be included in Cox models.</description>
        <time_frame>Up to 8 weeks</time_frame>
        <population>Due to the study's early termination and inadequate number of patients, no patients were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm I (Placebo, Cisplatin, and Radiotherapy)</title>
            <description>Patients receive placebo PO twice daily in week 1 and then once daily in weeks 2-11. Patients also receive cisplatin IV over 3 hours once in weeks 2, 5, and 8 and undergo radiotherapy 5 days a week in weeks 2-8.&#xD;
placebo: Given PO&#xD;
cisplatin: Given IV&#xD;
radiation therapy: Undergo radiotherapy&#xD;
quality-of-life assessment: Ancillary studies</description>
          </group>
          <group group_id="O2">
            <title>Arm II (Selenomethionine, Cisplatin, and Radiotherapy)</title>
            <description>Patients receive selenomethionine PO twice daily in week 1 and then once daily in weeks 2-11. Patients also receive cisplatin and undergo radiotherapy as in arm I.&#xD;
selenomethionine: Given PO&#xD;
cisplatin: Given IV&#xD;
radiation therapy: Undergo radiotherapy&#xD;
quality-of-life assessment: Ancillary studies</description>
          </group>
        </group_list>
        <measure>
          <title>CRT Dose Delivery</title>
          <description>This characteristic will be included in Cox models.</description>
          <population>Due to the study's early termination and inadequate number of patients, no patients were analyzed.</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>Plasma Cisplatin and Selenium PK and PD Markers (NZ Only)</title>
        <description>Descriptive statistics will be used to describe the mean plasma cisplatin and selenium at each time point. Repeated measures analysis of variance will be used to evaluate the changes in plasma cisplatin and selenium over time. Analysis of pharmacodynamic markers will be conducted using statistical methods appropriate for within-patient sequential analyses, such as repeated measures analysis of variance.</description>
        <time_frame>Up to 3 months post-treatment</time_frame>
        <population>Due to the study's early termination and inadequate number of patients, no patients were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm I (Placebo, Cisplatin, and Radiotherapy)</title>
            <description>Patients receive placebo PO twice daily in week 1 and then once daily in weeks 2-11. Patients also receive cisplatin IV over 3 hours once in weeks 2, 5, and 8 and undergo radiotherapy 5 days a week in weeks 2-8.&#xD;
placebo: Given PO&#xD;
cisplatin: Given IV&#xD;
radiation therapy: Undergo radiotherapy&#xD;
quality-of-life assessment: Ancillary studies</description>
          </group>
          <group group_id="O2">
            <title>Arm II (Selenomethionine, Cisplatin, and Radiotherapy)</title>
            <description>Patients receive selenomethionine PO twice daily in week 1 and then once daily in weeks 2-11. Patients also receive cisplatin and undergo radiotherapy as in arm I.&#xD;
selenomethionine: Given PO&#xD;
cisplatin: Given IV&#xD;
radiation therapy: Undergo radiotherapy&#xD;
quality-of-life assessment: Ancillary studies</description>
          </group>
        </group_list>
        <measure>
          <title>Plasma Cisplatin and Selenium PK and PD Markers (NZ Only)</title>
          <description>Descriptive statistics will be used to describe the mean plasma cisplatin and selenium at each time point. Repeated measures analysis of variance will be used to evaluate the changes in plasma cisplatin and selenium over time. Analysis of pharmacodynamic markers will be conducted using statistical methods appropriate for within-patient sequential analyses, such as repeated measures analysis of variance.</description>
          <population>Due to the study's early termination and inadequate number of patients, no patients were analyzed.</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_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Arm I (Placebo, Cisplatin, and Radiotherapy)</title>
          <description>Patients receive placebo PO twice daily in week 1 and then once daily in weeks 2-11. Patients also receive cisplatin IV over 3 hours once in weeks 2, 5, and 8 and undergo radiotherapy 5 days a week in weeks 2-8.&#xD;
placebo: Given PO&#xD;
cisplatin: Given IV&#xD;
radiation therapy: Undergo radiotherapy&#xD;
quality-of-life assessment: Ancillary studies</description>
        </group>
        <group group_id="E2">
          <title>Arm II (Selenomethionine, Cisplatin, and Radiotherapy)</title>
          <description>Patients receive selenomethionine PO twice daily in week 1 and then once daily in weeks 2-11. Patients also receive cisplatin and undergo radiotherapy as in arm I.&#xD;
selenomethionine: Given PO&#xD;
cisplatin: Given IV&#xD;
radiation therapy: Undergo radiotherapy&#xD;
quality-of-life assessment: Ancillary studies</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Leukopenia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Ventricular tachycardia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Stomatitis</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Mucosal inflammation</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood creatine increased</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Blood sodium abnormal</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Haemoglobin decreased</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Cerebrovascular accident</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="6" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pharyngolaryngeal pain</sub_title>
                <counts group_id="E1" events="6" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Orthostatic hypotension</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Leukopenia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="9" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Lymphopenia</sub_title>
                <counts group_id="E1" events="18" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E2" events="27" subjects_affected="3" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>White blood cell disorder</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Angina pectoris</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Deafness</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Ear pain</sub_title>
                <counts group_id="E1" events="6" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hypoacusis</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Otorrhoea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Tinnitus</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="12" subjects_affected="3" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Diplopia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal discomfort</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="24" subjects_affected="5" subjects_at_risk="8"/>
                <counts group_id="E2" events="30" subjects_affected="6" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="21" subjects_affected="3" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" events="15" subjects_affected="5" subjects_at_risk="8"/>
                <counts group_id="E2" events="15" subjects_affected="5" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" events="21" subjects_affected="5" subjects_at_risk="8"/>
                <counts group_id="E2" events="15" subjects_affected="5" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Glossodynia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Lip disorder</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Mouth ulceration</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="24" subjects_affected="5" subjects_at_risk="8"/>
                <counts group_id="E2" events="27" subjects_affected="8" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Odynophagia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="6" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Oesophageal stenosis</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Oral pain</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Reflux gastritis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="6" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Salivary hypersecretion</sub_title>
                <counts group_id="E1" events="9" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Stomatitis</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="6" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="9" subjects_affected="3" subjects_at_risk="8"/>
                <counts group_id="E2" events="6" subjects_affected="2" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="21" subjects_affected="5" subjects_at_risk="8"/>
                <counts group_id="E2" events="39" subjects_affected="6" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Fibrosis</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Localised oedema</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="6" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Mucosal inflammation</sub_title>
                <counts group_id="E1" events="24" subjects_affected="4" subjects_at_risk="8"/>
                <counts group_id="E2" events="30" subjects_affected="6" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="6" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E2" events="6" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Secretion discharge</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Oral candidiasis</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Perianal abscess</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Radiation skin injury</sub_title>
                <counts group_id="E1" events="15" subjects_affected="4" subjects_at_risk="8"/>
                <counts group_id="E2" events="9" subjects_affected="3" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Blood bilirubin abnormal</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="6" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Blood creatine increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Blood creatinine increased</sub_title>
                <counts group_id="E1" events="6" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Blood sodium abnormal</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Haemoglobin</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Haemoglobin decreased</sub_title>
                <counts group_id="E1" events="9" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E2" events="27" subjects_affected="4" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" events="6" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="9" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" events="6" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E2" events="9" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>White blood cell count decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" events="18" subjects_affected="4" subjects_at_risk="8"/>
                <counts group_id="E2" events="12" subjects_affected="3" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="9" subjects_affected="3" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hyperkalaemia</sub_title>
                <counts group_id="E1" events="15" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hypermagnesaemia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hypoalbuminaemia</sub_title>
                <counts group_id="E1" events="6" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hypocalcaemia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" events="6" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E2" events="6" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hypomagnesaemia</sub_title>
                <counts group_id="E1" events="21" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" events="6" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="18" subjects_affected="4" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Oral intake reduced</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Musculoskeletal pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Neck pain</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="6" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Trismus</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Ageusia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="6" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Dysarthria</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" events="12" subjects_affected="4" subjects_at_risk="8"/>
                <counts group_id="E2" events="21" subjects_affected="6" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Facial paresis</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="12" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Peripheral sensory neuropathy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Urinary retention</sub_title>
                <counts group_id="E1" events="6" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Aspiration</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="6" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="6" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E2" events="9" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Dysphonia</sub_title>
                <counts group_id="E1" events="6" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E2" events="6" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hiccups</sub_title>
                <counts group_id="E1" events="6" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Increased upper airway secretion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="18" subjects_affected="5" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Pharyngolaryngeal pain</sub_title>
                <counts group_id="E1" events="18" subjects_affected="4" subjects_at_risk="8"/>
                <counts group_id="E2" events="24" subjects_affected="6" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Drug eruption</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Dry skin</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="6" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Erythema</sub_title>
                <counts group_id="E1" events="18" subjects_affected="4" subjects_at_risk="8"/>
                <counts group_id="E2" events="30" subjects_affected="7" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Exfoliative rash</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Rash generalised</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Orthostatic hypotension</sub_title>
                <counts group_id="E1" events="6" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Thrombosis</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>Due to the study's early termination and inadequate number of patients, no patients were analyzed.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Senior Administrator, Compliance - Clinical Research Services</name_or_title>
      <organization>Roswell Park Cancer Institute</organization>
      <phone>716-845-2300</phone>
    </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/NCT01682031
org study id: I 107807
secondary id: NCI-2009-01503
nct id: NCT01682031
nct alias: NCT00935038
lead sponsor: 
collaborator: 
has dmc: Yes
This randomized phase II trial is studying how well selenomethionine (SLM) works in reducing
      mucositis in patients with locally advanced head and neck cancer who are receiving cisplatin
      and radiation therapy. SLM may help prevent or reduce mucositis, or mouth sores, in patients
      receiving chemotherapy and radiation therapy. It is not yet known whether SLM is more
      effective than a placebo in reducing mucositis
PRIMARY OBJECTIVES:

      I. To assess whether SLM reduces the incidence of grade 3 or 4 mucositis in head and neck
      squamous cell carcinoma (HNSCC) patients treated with concurrent chemoradiation (CRT) over 7
      weeks.

      SECONDARY OBJECTIVES:

      I. To assess the impact of SLM on tumor complete response rate, relapse-free survival,
      overall survival and quality of life.

      II. To assess whether SLM reduces the incidence and severity of treatment-related toxicities
      including xerostomia, renal impairment and myelosuppression.

      III. To assess whether SLM improves chemoradiation dose delivery. IV. To determine safety of
      SLM at this dose. V. In New Zealand (NZ) patients only, to assess the impact of SLM on plasma
      free cisplatin and plasma selenium pharmacokinetics (PK) and on pharmacodynamic (PD) markers
      of biological activity of selenium.

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

      ARM I: Patients receive placebo orally (PO) twice daily in week 1 and then once daily in
      weeks 2-11. Patients also receive cisplatin intravenously (IV) over 3 hours once in weeks 2,
      5, and 8 and undergo radiotherapy 5 days a week in weeks 2-8.

      ARM II: Patients receive selenomethionine PO twice daily in week 1 and then once daily in
      weeks 2-11. Patients also receive cisplatin and undergo radiotherapy as in arm I.

      After completion of study treatment, patients are followed up periodically.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Supportive Care
masking: Double
measure: Incidence of >= Grade 3 Mucositis
time frame: Up to 5 years
description: Will be compared as difference in proportions with 95% confidence intervals.
measure: Tumor Complete Response Rate
time frame: Up to 5 years post-treatment
description: Will be compared as difference in proportions with 95% confidence intervals. Disease will be measured according to the Response Evaluation Criteria in Solid Tumors (RECIST).
measure: Relapse-free Survival (RFS)
time frame: At 1 year
description: Assessed by Kaplan-Meier RFS curves and the proportion with an event at 1 year for RFS will be compared simultaneously to obtain more global sensitivity to differences in time-to-event.
measure: Overall Survival
time frame: Up to 5 years post-treatment
description: Estimated using the Kaplan-Meier method. Log-rank tests will be used for the comparison of survival distributions among study groups. Continuous endpoints will be summarized using means, standard deviations and percentiles.
measure: Quality of Life
time frame: Up to 1 year post-treatment
measure: Incidence of Grade 3 or 4 Treatment-related Toxicities, Including Xerostomia
time frame: Up to 5 years post-treatment
description: Will be compared as difference in proportions with 95% confidence intervals.
measure: CRT Dose Delivery
time frame: Up to 8 weeks
description: This characteristic will be included in Cox models.
measure: Plasma Cisplatin and Selenium PK and PD Markers (NZ Only)
time frame: Up to 3 months post-treatment
description: Descriptive statistics will be used to describe the mean plasma cisplatin and selenium at each time point. Repeated measures analysis of variance will be used to evaluate the changes in plasma cisplatin and selenium over time. Analysis of pharmacodynamic markers will be conducted using statistical methods appropriate for within-patient sequential analyses, such as repeated measures analysis of variance.
arm group label: Arm I (placebo, cisplatin, and radiotherapy)
arm group type: Placebo Comparator
description: Patients receive placebo PO twice daily in week 1 and then once daily in weeks 2-11. Patients also receive cisplatin IV over 3 hours once in weeks 2, 5, and 8 and undergo radiotherapy 5 days a week in weeks 2-8.
arm group label: Arm II (selenomethionine, cisplatin, and radiotherapy)
arm group type: Experimental
description: Patients receive selenomethionine PO twice daily in week 1 and then once daily in weeks 2-11. Patients also receive cisplatin and undergo radiotherapy as in arm I.
intervention type: Dietary Supplement
intervention name: selenomethionine
description: Given PO
arm group label: Arm II (selenomethionine, cisplatin, and radiotherapy)
intervention type: Other
intervention name: placebo
description: Given PO
arm group label: Arm I (placebo, cisplatin, and radiotherapy)
other name: PLCB
intervention type: Drug
intervention name: cisplatin
description: Given IV
arm group label: Arm I (placebo, cisplatin, and radiotherapy)
arm group label: Arm II (selenomethionine, cisplatin, and radiotherapy)
other name: CACP
other name: CDDP
other name: CPDD
other name: DDP
intervention type: Radiation
intervention name: radiation therapy
description: Undergo radiotherapy
arm group label: Arm I (placebo, cisplatin, and radiotherapy)
arm group label: Arm II (selenomethionine, cisplatin, and radiotherapy)
other name: irradiation
other name: radiotherapy
other name: therapy, radiation
intervention type: Procedure
intervention name: quality-of-life assessment
description: Ancillary studies
arm group label: Arm I (placebo, cisplatin, and radiotherapy)
arm group label: Arm II (selenomethionine, cisplatin, and radiotherapy)
other name: quality of life assessment
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Anurag Singh
role: Principal Investigator
affiliation: Roswell Park Cancer Institute
facility: 
facility: 
country: New Zealand
country: United States
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Squamous Cell
mesh term: Laryngeal Neoplasms
mesh term: Oropharyngeal Neoplasms
mesh term: Squamous Cell Carcinoma of Head and Neck
mesh term: Nasopharyngeal Carcinoma
mesh term: Paranasal Sinus Neoplasms
mesh term: Mucositis
mesh term: Xerostomia
mesh term: Laryngeal Diseases
mesh term: Selenium
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Due to the study's early termination and inadequate number of patients, no patients were analyzed.
point of contact: 