<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/NCT03269344</url>
  </required_header>
  <id_info>
    <org_study_id>HFHS-Gabapentin/RT Study</org_study_id>
    <nct_id>NCT03269344</nct_id>
  </id_info>
  <brief_title>Gabapentin for the Reduction of Radiation Therapy Induced Pain During the Treatment of Oropharyngeal Cancer</brief_title>
  <official_title>Randomized Phase III, Double-Blind, Placebo Controlled Study of Prophylactic Gabapentin for the Reduction of Radiation Therapy Induced Pain During the Treatment of Oropharyngeal Squamous Cell Carcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Henry Ford Health System</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Henry Ford Health System</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Strategies to minimize and mitigate external beam radiation therapy related mucositis and&#xD;
      pain during the treatment of head and neck cancer remain limited. The investigators&#xD;
      hypothesize that gabapentin could be used to delay or reduce treatment-related pain, reliance&#xD;
      on opioid medication, and improve the quality of life for these patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The specific aims of this proposed study include the following:&#xD;
&#xD;
        -  Evaluate the reduction or delay of mucositis related pain and morbidity with the use of&#xD;
           gabapentin in patients with stage III or IV oropharyngeal squamous cell carcinoma&#xD;
           undergoing definitive radiation with concurrent chemotherapy as part of their cancer&#xD;
           management, compared to standard supportive side effect mitigation - using patient&#xD;
           reported quality of life endpoints such as the Patient-Reported Oral Mucositis Symptoms&#xD;
           (PROMS) scale.&#xD;
&#xD;
        -  Assess morphine-equivalent opioid use in both treatment arms by collecting the patient's&#xD;
           narcotic use in the previous 24-hour period at each weekly evaluation during radiation&#xD;
           treatment.&#xD;
&#xD;
        -  Report on change in Speech and swallow performance, as measured by the Performance&#xD;
           Status Scale (PSS) for Head and Neck Cancer Patients&#xD;
&#xD;
        -  Evaluate changes in weight from baseline throughout treatment between the two arms.&#xD;
&#xD;
        -  Assess feeding tube requirements during treatment.&#xD;
&#xD;
        -  Evaluate the adverse events associated with gabapentin.&#xD;
&#xD;
        -  Evaluate the severity of radiation mucositis (grade 3-4, CTCAE, v. 4)&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 5, 2017</start_date>
  <completion_date type="Actual">December 9, 2020</completion_date>
  <primary_completion_date type="Actual">December 9, 2020</primary_completion_date>
  <phase>Phase 3</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Quality of Life From Mucositis-related Pain Measured by the Patient-Reported Oral Mucositis Symptoms (PROMS) Scale From Baseline to Follow-up</measure>
    <time_frame>Evaluated change in scores from baseline to 6 weeks post-treatment, approximately 13 weeks</time_frame>
    <description>Scale tile: Patient Reported Oral Mucositis Symptoms scale, range 0-1000, higher scores indicate worse outcomes</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Total FACT-HN Scores From Baseline to Follow-up</measure>
    <time_frame>Administered at baseline and at 6-week follow-up endpoint, approximately 13 weeks</time_frame>
    <description>Scale: Functional Assessment of Cancer Therapy-Trial Outcome (FACT-HN), range 0-148, higher scores indicate better outcomes</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Average Opioid Use, Measured in Morphine Equivalents Per Day.</measure>
    <time_frame>Over the entire study period from baseline to follow-up, approximately 13 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in PRO-CTCAE Scores From Baseline to Follow-up</measure>
    <time_frame>Evaluated change in scores from baseline to 6 weeks post-treatment, approximately 13 weeks</time_frame>
    <description>Scale: Patient-reported outcomes of Common Terminology Criteria for Adverse Events (PRO-CTCAE), 5-point Likert scale, higher scores indicate worse outcomes. Range of scores 0-40 (min-max).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Weight Lost</measure>
    <time_frame>Percent change from baseline to week 7 of treatment</time_frame>
    <description>Percent weight lost from baseline to week 7 of treatment (end of treatment)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Feeding Tube Placement</measure>
    <time_frame>Evaluated placement of feeding tube from baseline (start of radiation) to 6 weeks post-treatment, approximately 13 weeks</time_frame>
    <description>Measure of number of patients who required feeding tube placement at any time during the study period</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">65</enrollment>
  <condition>Oropharynx Cancer</condition>
  <arm_group>
    <arm_group_label>Control Arm</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Standard supportive care during definitive treatment plus placebo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Experimental Arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Gabapentin plus standard supportive care</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Gabapentin</intervention_name>
    <description>Gabapentin is an anticonvulsant and has been used to manage neuropathic pain and is FDA-approved for the treatment of post-herpetic neuralgia and partial onset seizures</description>
    <arm_group_label>Experimental Arm</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo Oral Capsule</intervention_name>
    <description>Placebo</description>
    <arm_group_label>Control Arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients being treated with combination chemotherapy and radiation therapy daily for&#xD;
             locally advanced (stage III-IV) squamous cell carcinoma of the oropharynx.&#xD;
&#xD;
          -  Age ≥ 18.&#xD;
&#xD;
          -  ECOG performance status ≤ 1.&#xD;
&#xD;
          -  Patients must provide study specific informed consent prior to study entry and be able&#xD;
             to fill out toxicity and quality of life related questionnaires.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients may not be receiving gabapentin, any other investigational agents, or other&#xD;
             anticonvulsants.&#xD;
&#xD;
          -  Patients with metastatic disease are excluded from this clinical trial.&#xD;
&#xD;
          -  Patient with allergies or hypersensitivity to gabapentin.&#xD;
&#xD;
          -  Patients receiving surgery as part of their definitive management.&#xD;
&#xD;
          -  Patients who have received prior chemotherapy or radiation therapy.&#xD;
&#xD;
          -  Patients unable to complete the required forms; however, verbal completion is adequate&#xD;
             if recorded on the form daily.&#xD;
&#xD;
          -  Uncontrolled serious illness including, but not limited to, ongoing or serious active&#xD;
             infection requiring IV antibiotics for over 30 days, symptomatic congestive heart&#xD;
             failure, unstable angina pectoris, cardiac arrhythmia other than chronic, stable&#xD;
             atrial fibrillation, or psychiatric illness/social situations that would limit&#xD;
             compliance with study requirements.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Farzan Siddiqui, MD PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Henry Ford Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Henry Ford Hospital</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2022</verification_date>
  <study_first_submitted>June 5, 2017</study_first_submitted>
  <study_first_submitted_qc>August 30, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 31, 2017</study_first_posted>
  <results_first_submitted>November 22, 2021</results_first_submitted>
  <results_first_submitted_qc>December 20, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">January 20, 2022</results_first_posted>
  <last_update_submitted>January 19, 2022</last_update_submitted>
  <last_update_submitted_qc>January 19, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">January 26, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Henry Ford Health System</investigator_affiliation>
    <investigator_full_name>Andrew Cook</investigator_full_name>
    <investigator_title>Resident Physcian</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Oropharyngeal Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Gabapentin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <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>February 6, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/44/NCT03269344/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>After 65 patients were enrolled, 7 more were excluded from analysis, leaving 58 patients analyzed. These patients were excluded because they received immunotherapy (n=1), pursued treatment elsewhere (n=2), developed acute kidney injury (n=1), and refused to take medication during the first two weeks of treatment (n=3).</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Control Arm</title>
          <description>Standard supportive care during definitive treatment plus placebo&#xD;
Placebo Oral Capsule: Placebo</description>
        </group>
        <group group_id="P2">
          <title>Experimental Arm</title>
          <description>Gabapentin plus standard supportive care&#xD;
Gabapentin: Gabapentin is an anticonvulsant and has been used to manage neuropathic pain and is FDA-approved for the treatment of post-herpetic neuralgia and partial onset seizures</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="33"/>
                <participants group_id="P2" count="32"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="29"/>
                <participants group_id="P2" count="29"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Control Arm</title>
          <description>Standard supportive care during definitive treatment plus placebo&#xD;
Placebo Oral Capsule: Placebo</description>
        </group>
        <group group_id="B2">
          <title>Experimental Arm</title>
          <description>Gabapentin plus standard supportive care&#xD;
Gabapentin: Gabapentin is an anticonvulsant and has been used to manage neuropathic pain and is FDA-approved for the treatment of post-herpetic neuralgia and partial onset seizures</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="29"/>
            <count group_id="B2" value="29"/>
            <count group_id="B3" value="58"/>
          </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="59.4" spread="8.5"/>
                    <measurement group_id="B2" value="60.2" spread="10.4"/>
                    <measurement group_id="B3" value="59.8" spread="9.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="25"/>
                    <measurement group_id="B2" value="24"/>
                    <measurement group_id="B3" value="49"/>
                  </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="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </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="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="25"/>
                    <measurement group_id="B2" value="25"/>
                    <measurement group_id="B3" value="50"/>
                  </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="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Smoking Status</title>
          <description>Stratification variable</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Primary Site</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Oropharynx-base of tongue</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="21"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Oropharynx-soft palate</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>
                  <title>Oropharynx-tonsil</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="29"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Oropharynx-vallecula</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Oropharynx-not specified</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown primary</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>HPV Status</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Negative</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Positive</title>
                  <measurement_list>
                    <measurement group_id="B1" value="23"/>
                    <measurement group_id="B2" value="26"/>
                    <measurement group_id="B3" value="49"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown</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>Clinical T Stage</title>
          <description>Patients were staged according to the American Joint Committee on Cancer staging system 8th edition (2017) for oropharyngeal tumors. Higher numbers indicated higher stage/more advanced tumors.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>1</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="14"/>
                  </measurement_list>
                </category>
                <category>
                  <title>2</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="21"/>
                  </measurement_list>
                </category>
                <category>
                  <title>3</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>4</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>4a</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>
                  <title>4b</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>
                  <title>Tx or T0</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>Clinical N Stage</title>
          <description>Patients were staged according to the American Joint Committee on Cancer staging system 8th edition (2017) for oropharyngeal tumors. Higher numbers indicated higher stage/more advanced tumors.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>0</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>1</title>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="32"/>
                  </measurement_list>
                </category>
                <category>
                  <title>2</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="13"/>
                  </measurement_list>
                </category>
                <category>
                  <title>2a</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>2b</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>2c</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>3</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Type of Chemotherapy</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Carboplatin-based</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Cisplatin every 3 weeks</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="32"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Cisplatin weekly</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Opioid Use at Baseline</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Gross Tumor Volume of Primary Tumor</title>
          <units>cubic centimeter (cc)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="22.0" spread="17.2"/>
                    <measurement group_id="B2" value="21.5" spread="18.5"/>
                    <measurement group_id="B3" value="21.8" spread="17.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Gross Tumor Volume Total (cc)</title>
          <units>cc</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="50.3" spread="40.8"/>
                    <measurement group_id="B2" value="49.2" spread="31.5"/>
                    <measurement group_id="B3" value="49.8" spread="36.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Quality of Life From Mucositis-related Pain Measured by the Patient-Reported Oral Mucositis Symptoms (PROMS) Scale From Baseline to Follow-up</title>
        <description>Scale tile: Patient Reported Oral Mucositis Symptoms scale, range 0-1000, higher scores indicate worse outcomes</description>
        <time_frame>Evaluated change in scores from baseline to 6 weeks post-treatment, approximately 13 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Control Arm</title>
            <description>Standard supportive care during definitive treatment plus placebo&#xD;
Placebo Oral Capsule: Placebo</description>
          </group>
          <group group_id="O2">
            <title>Experimental Arm</title>
            <description>Gabapentin plus standard supportive care&#xD;
Gabapentin: Gabapentin is an anticonvulsant and has been used to manage neuropathic pain and is FDA-approved for the treatment of post-herpetic neuralgia and partial onset seizures</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Quality of Life From Mucositis-related Pain Measured by the Patient-Reported Oral Mucositis Symptoms (PROMS) Scale From Baseline to Follow-up</title>
          <description>Scale tile: Patient Reported Oral Mucositis Symptoms scale, range 0-1000, higher scores indicate worse outcomes</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
                <count group_id="O2" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20.1" spread="16.8"/>
                    <measurement group_id="O2" value="29.1" spread="22.5"/>
                  </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>0.11</p_value>
            <method>ANOVA</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Total FACT-HN Scores From Baseline to Follow-up</title>
        <description>Scale: Functional Assessment of Cancer Therapy-Trial Outcome (FACT-HN), range 0-148, higher scores indicate better outcomes</description>
        <time_frame>Administered at baseline and at 6-week follow-up endpoint, approximately 13 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Control Arm</title>
            <description>Standard supportive care during definitive treatment plus placebo&#xD;
Placebo Oral Capsule: Placebo</description>
          </group>
          <group group_id="O2">
            <title>Experimental Arm</title>
            <description>Gabapentin plus standard supportive care&#xD;
Gabapentin: Gabapentin is an anticonvulsant and has been used to manage neuropathic pain and is FDA-approved for the treatment of post-herpetic neuralgia and partial onset seizures</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Total FACT-HN Scores From Baseline to Follow-up</title>
          <description>Scale: Functional Assessment of Cancer Therapy-Trial Outcome (FACT-HN), range 0-148, higher scores indicate better outcomes</description>
          <units>units on a scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
                <count group_id="O2" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-15.0" lower_limit="-19.5" upper_limit="-2.5"/>
                    <measurement group_id="O2" value="-20.0" lower_limit="-25.8" upper_limit="-11.8"/>
                  </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>0.08</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Average Opioid Use, Measured in Morphine Equivalents Per Day.</title>
        <time_frame>Over the entire study period from baseline to follow-up, approximately 13 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Control Arm</title>
            <description>Standard supportive care during definitive treatment plus placebo&#xD;
Placebo Oral Capsule: Placebo</description>
          </group>
          <group group_id="O2">
            <title>Experimental Arm</title>
            <description>Gabapentin plus standard supportive care&#xD;
Gabapentin: Gabapentin is an anticonvulsant and has been used to manage neuropathic pain and is FDA-approved for the treatment of post-herpetic neuralgia and partial onset seizures</description>
          </group>
        </group_list>
        <measure>
          <title>Average Opioid Use, Measured in Morphine Equivalents Per Day.</title>
          <units>Daily morphine equivalents</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
                <count group_id="O2" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15.6" lower_limit="6.7" upper_limit="32.2"/>
                    <measurement group_id="O2" value="22.2" lower_limit="13.3" upper_limit="35.0"/>
                  </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>0.32</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in PRO-CTCAE Scores From Baseline to Follow-up</title>
        <description>Scale: Patient-reported outcomes of Common Terminology Criteria for Adverse Events (PRO-CTCAE), 5-point Likert scale, higher scores indicate worse outcomes. Range of scores 0-40 (min-max).</description>
        <time_frame>Evaluated change in scores from baseline to 6 weeks post-treatment, approximately 13 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Control Arm</title>
            <description>Standard supportive care during definitive treatment plus placebo&#xD;
Placebo Oral Capsule: Placebo</description>
          </group>
          <group group_id="O2">
            <title>Experimental Arm</title>
            <description>Gabapentin plus standard supportive care&#xD;
Gabapentin: Gabapentin is an anticonvulsant and has been used to manage neuropathic pain and is FDA-approved for the treatment of post-herpetic neuralgia and partial onset seizures</description>
          </group>
        </group_list>
        <measure>
          <title>Change in PRO-CTCAE Scores From Baseline to Follow-up</title>
          <description>Scale: Patient-reported outcomes of Common Terminology Criteria for Adverse Events (PRO-CTCAE), 5-point Likert scale, higher scores indicate worse outcomes. Range of scores 0-40 (min-max).</description>
          <units>units on a scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
                <count group_id="O2" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.0" lower_limit="-2.0" upper_limit="6.0"/>
                    <measurement group_id="O2" value="6.5" lower_limit="3.5" upper_limit="11.8"/>
                  </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>&lt;0.01</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Weight Lost</title>
        <description>Percent weight lost from baseline to week 7 of treatment (end of treatment)</description>
        <time_frame>Percent change from baseline to week 7 of treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Control Arm</title>
            <description>Standard supportive care during definitive treatment plus placebo&#xD;
Placebo Oral Capsule: Placebo</description>
          </group>
          <group group_id="O2">
            <title>Experimental Arm</title>
            <description>Gabapentin plus standard supportive care&#xD;
Gabapentin: Gabapentin is an anticonvulsant and has been used to manage neuropathic pain and is FDA-approved for the treatment of post-herpetic neuralgia and partial onset seizures</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Weight Lost</title>
          <description>Percent weight lost from baseline to week 7 of treatment (end of treatment)</description>
          <units>Percent change</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
                <count group_id="O2" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-10.7" lower_limit="-14.4" upper_limit="-7.8"/>
                    <measurement group_id="O2" value="-11.4" lower_limit="-15.6" upper_limit="-8.0"/>
                  </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>0.81</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Feeding Tube Placement</title>
        <description>Measure of number of patients who required feeding tube placement at any time during the study period</description>
        <time_frame>Evaluated placement of feeding tube from baseline (start of radiation) to 6 weeks post-treatment, approximately 13 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Control Arm</title>
            <description>Standard supportive care during definitive treatment plus placebo&#xD;
Placebo Oral Capsule: Placebo</description>
          </group>
          <group group_id="O2">
            <title>Experimental Arm</title>
            <description>Gabapentin plus standard supportive care&#xD;
Gabapentin: Gabapentin is an anticonvulsant and has been used to manage neuropathic pain and is FDA-approved for the treatment of post-herpetic neuralgia and partial onset seizures</description>
          </group>
        </group_list>
        <measure>
          <title>Feeding Tube Placement</title>
          <description>Measure of number of patients who required feeding tube placement at any time during the study period</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="29"/>
                <count group_id="O2" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="18"/>
                  </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>&lt;0.01</p_value>
            <method>Chi-squared</method>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse effects data were collected from baseline, throughout the 7 week treatment course, and at the 6-week post-treatment follow-up timepoint. Thus, this time period was about 14 weeks.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Control Arm</title>
          <description>Standard supportive care during definitive treatment plus placebo&#xD;
Placebo Oral Capsule: Placebo</description>
        </group>
        <group group_id="E2">
          <title>Experimental Arm</title>
          <description>Gabapentin plus standard supportive care&#xD;
Gabapentin: Gabapentin is an anticonvulsant and has been used to manage neuropathic pain and is FDA-approved for the treatment of post-herpetic neuralgia and partial onset seizures</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Andrew Cook</name_or_title>
      <organization>Henry Ford Cancer Institute</organization>
      <phone>3135568400</phone>
      <email>acook11@hfhs.org</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/NCT03269344
org study id: HFHS-Gabapentin/RT Study
nct id: NCT03269344
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
Strategies to minimize and mitigate external beam radiation therapy related mucositis and
      pain during the treatment of head and neck cancer remain limited. The investigators
      hypothesize that gabapentin could be used to delay or reduce treatment-related pain, reliance
      on opioid medication, and improve the quality of life for these patients.
The specific aims of this proposed study include the following:

        -  Evaluate the reduction or delay of mucositis related pain and morbidity with the use of
           gabapentin in patients with stage III or IV oropharyngeal squamous cell carcinoma
           undergoing definitive radiation with concurrent chemotherapy as part of their cancer
           management, compared to standard supportive side effect mitigation - using patient
           reported quality of life endpoints such as the Patient-Reported Oral Mucositis Symptoms
           (PROMS) scale.

        -  Assess morphine-equivalent opioid use in both treatment arms by collecting the patient's
           narcotic use in the previous 24-hour period at each weekly evaluation during radiation
           treatment.

        -  Report on change in Speech and swallow performance, as measured by the Performance
           Status Scale (PSS) for Head and Neck Cancer Patients

        -  Evaluate changes in weight from baseline throughout treatment between the two arms.

        -  Assess feeding tube requirements during treatment.

        -  Evaluate the adverse events associated with gabapentin.

        -  Evaluate the severity of radiation mucositis (grade 3-4, CTCAE, v. 4)
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Supportive Care
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change in Quality of Life From Mucositis-related Pain Measured by the Patient-Reported Oral Mucositis Symptoms (PROMS) Scale From Baseline to Follow-up
time frame: Evaluated change in scores from baseline to 6 weeks post-treatment, approximately 13 weeks
description: Scale tile: Patient Reported Oral Mucositis Symptoms scale, range 0-1000, higher scores indicate worse outcomes
measure: Change in Total FACT-HN Scores From Baseline to Follow-up
time frame: Administered at baseline and at 6-week follow-up endpoint, approximately 13 weeks
description: Scale: Functional Assessment of Cancer Therapy-Trial Outcome (FACT-HN), range 0-148, higher scores indicate better outcomes
measure: Average Opioid Use, Measured in Morphine Equivalents Per Day.
time frame: Over the entire study period from baseline to follow-up, approximately 13 weeks
measure: Change in PRO-CTCAE Scores From Baseline to Follow-up
time frame: Evaluated change in scores from baseline to 6 weeks post-treatment, approximately 13 weeks
description: Scale: Patient-reported outcomes of Common Terminology Criteria for Adverse Events (PRO-CTCAE), 5-point Likert scale, higher scores indicate worse outcomes. Range of scores 0-40 (min-max).
measure: Percent Weight Lost
time frame: Percent change from baseline to week 7 of treatment
description: Percent weight lost from baseline to week 7 of treatment (end of treatment)
measure: Feeding Tube Placement
time frame: Evaluated placement of feeding tube from baseline (start of radiation) to 6 weeks post-treatment, approximately 13 weeks
description: Measure of number of patients who required feeding tube placement at any time during the study period
arm group label: Control Arm
arm group type: Placebo Comparator
description: Standard supportive care during definitive treatment plus placebo
arm group label: Experimental Arm
arm group type: Experimental
description: Gabapentin plus standard supportive care
intervention type: Drug
intervention name: Gabapentin
description: Gabapentin is an anticonvulsant and has been used to manage neuropathic pain and is FDA-approved for the treatment of post-herpetic neuralgia and partial onset seizures
arm group label: Experimental Arm
intervention type: Drug
intervention name: Placebo Oral Capsule
description: Placebo
arm group label: Control Arm
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Farzan Siddiqui, MD PhD
role: Study Chair
affiliation: Henry Ford Hospital
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Henry Ford Health System
investigator full name: Andrew Cook
investigator title: Resident Physcian
mesh term: Oropharyngeal Neoplasms
mesh term: Gabapentin
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 