<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/NCT02229539</url>
  </required_header>
  <id_info>
    <org_study_id>A221304</org_study_id>
    <secondary_id>U10CA037447</secondary_id>
    <secondary_id>UG1CA189823</secondary_id>
    <secondary_id>NCI-2014-01877</secondary_id>
    <nct_id>NCT02229539</nct_id>
  </id_info>
  <brief_title>Doxepin and a Topical Rinse in the Treatment of Acute Oral Mucositis Pain in Patients Receiving Radiotherapy With or Without Chemotherapy</brief_title>
  <official_title>A Phase III Placebo-Controlled, Randomized Three-Arm Study of Doxepin and a Topical Rinse in the Treatment of Acute Oral Mucositis Pain in Patients Receiving Radiotherapy With or Without Chemotherapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Alliance for Clinical Trials in Oncology</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Alliance for Clinical Trials in Oncology</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to test whether a mouthwash made with a drug called doxepin can&#xD;
      reduce the pain caused by mouth sores resulting from radiation therapy. A number of mouth&#xD;
      rinse preparations exist for patients with treatment-related oral mucositis pain such as the&#xD;
      DLA rinse, an over-the-counter medication. This study will evaluate the effects of doxepin&#xD;
      compared to DLA (diphenhydramine, lidocaine and antacids) and placebo.Doxepin is approved by&#xD;
      the Food and Drug Administration (FDA) for the treatment of depression, anxiety, long-term&#xD;
      pain management, as well as management of rash.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients are stratified according to sex (male vs. female), concurrent use of chemotherapy&#xD;
      (no vs. yes), patient age at registration (&lt; 60 years old vs. ≥ 60 years old and RTOG acute&#xD;
      radiation morbidity criteria (1 vs. 2 vs 3 or more). Protocol therapy will consist of 2&#xD;
      cycles. Patients are randomized to one of three treatment regimens, which include doxepin,&#xD;
      DLA and placebo. Cycle One will consist of one day. The care provider or nurse will confirm&#xD;
      that the oral pain is at least 4 out of 10 severity level at the time of the rinse on the&#xD;
      first day of the study. Patient will be asked to complete the baseline evaluation in the Oral&#xD;
      Symptoms booklet. If the pain score is less than 4 then administration will be delayed until&#xD;
      the pain is at least 4. Cycle Two will consist of an optional continuation phase lasting up&#xD;
      to 7 days. Initiation of the Cycle 2/Continuation Phase may be delayed up to one week after&#xD;
      Cycle 1/Day 1.&#xD;
&#xD;
      Primary Objective:&#xD;
&#xD;
      1. Determine whether the doxepin rinse or DLA rinse is more effective than placebo in&#xD;
      reducing OM-related pain in patients undergoing RT to the oral cavity, as measured by a&#xD;
      patient-reported questionnaire at baseline, 5 minutes, 15 minutes, 30 minutes, 1 hour, 2&#xD;
      hours, and 4 hours.&#xD;
&#xD;
      Secondary Objectives:&#xD;
&#xD;
        1. Assess the adverse event profile of the doxepin rinse, the DLA rinse agent, and the&#xD;
           placebo using a patient-reported questionnaire at 5 minutes, 15 minutes, 30 minutes, 1&#xD;
           hour, 2 hours, and 4 hours for domains of unpleasant taste, burning or stinging&#xD;
           discomfort, and drowsiness.&#xD;
&#xD;
        2. Compare the incidence of using additional analgesics between 1 and 4 hours after the&#xD;
           initial mouthwash, between the doxepin oral rinse, the DLA rinse agent, and the placebo&#xD;
           arms.&#xD;
&#xD;
        3. Compare the length of time that each study product is used by patients in the one-week&#xD;
           continuation phase.&#xD;
&#xD;
        4. Compare the daily pain scores in the one-week continuation phase for the three study&#xD;
           arms.&#xD;
&#xD;
        5. Compare the 24-hour morphine equivalent dose used in the continuation phase for the&#xD;
           three study arms.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 2014</start_date>
  <completion_date type="Actual">March 15, 2019</completion_date>
  <primary_completion_date type="Actual">May 2016</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>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Mean Area Under the Curve (AUC) of Total Pain Reduction</measure>
    <time_frame>Baseline, 5, 15, 30, 60, 120, 240 minutes post treatment</time_frame>
    <description>Total pain reduction (mouth and throat) was measured by the numerical analogue scale of mouth pain on a scale of 0 to 10, with 0=no pain and 10=worst pain in the questionnaires taken at baseline, and 5, 15, 30, 60, 120, 240 minutes after assigned treatment for doxepin or DLA vs. placebo. The total pain reduction was calculated by the (average of mouth and throat) area under the curve (AUC) adjusting for baseline, with time scale (baseline, 5, 15, 30, 60, 120 and 240 minutes post treatment) replaced by a numerical scale of 0, 1, 2, 3, 4, 5 and 6 respectively. The AUC was prorated when there are terminal missing data. If the missing data were intermittent, simple imputation by trapezoidal rules were applied to calculate the AUC. If a patient cancelled, was missing baseline data, or only provided baseline data, he/she was excluded from the statistical analysis.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The Total Unpleasant Taste of the Oral Rinse as Measured by the Numerical Analogue Scale of Taste of the Oral Rinse in the Questionnaires</measure>
    <time_frame>Up to 4 hours post-treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Total Stinging or Burning From the Oral Rinse as Measured by the Numerical Analogue Scale of Stinging or Burning From the Oral Rinse in the Questionnaires</measure>
    <time_frame>Up to 4 hours post-treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Total Drowsiness Increase as Measured by the Numerical Analogue Scale of Drowsiness Questionnaires</measure>
    <time_frame>Up to 4 hours post-treatment every 4 hours while on treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Incidence of Using Alternative Analgesics Between 1 and 4 Hours After Initial Mouthwash</measure>
    <time_frame>Up to 4 hours post-treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient Preference for Continued Therapy With Oral Rinse After Initial Test Rinse Phase, as Measured by Item 9 in the Patient-reported Questionnaire After 4 Hours</measure>
    <time_frame>Up to 4 hours post-treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Length of Time in the Continuation Phase</measure>
    <time_frame>Up to 4 hours post-treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pain Score in the Continuation Phase</measure>
    <time_frame>Up to 4 hours post-treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Alternative Analgesics Use in the Continuation Phase</measure>
    <time_frame>Up to 4 hours post-treatment</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">275</enrollment>
  <condition>Acute Oral Mucositis Pain</condition>
  <arm_group>
    <arm_group_label>doxepin rinse</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive 2.5 mL (25 mg) doxepin and 2.5 mL water orally. Doxepin rinse is administered in the clinic on Day 1 (Cycle 1). There is an optional continuation phase within seven days following Day 1 (Cycle 1), patients will be encouraged to continue treatment with the study agent for an additional week (Cycle 2) where the patient takes the rinse at home every 4 hours. Chemotherapy is allowed during the continuation phase. Patients randomized to doxepin or placebo, they and their caregivers will continue to be blinded to the treatment.&#xD;
Patients will complete the Oral Symptoms booklet per the protocol.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>DLA (diphenhydramine, lidocaine and antacid) rinse</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients receive 5.0 mL DLA orally. DLA is administered in the clinic on Day 1 (Cycle 1). There is an optional continuation phase within seven days following Day 1 (Cycle 1), patients will be encouraged to continue treatment with the study agent for an additional week (Cycle 2) where the patient takes the rinse at home every 4 hours. Chemotherapy is allowed during the continuation phase. Patients receiving DLA during the continuation phase of the study, they and/or caregivers may be aware that they are receiving DLA.&#xD;
Patients will complete the Oral Symptoms booklet per the protocol.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>placebo rinse</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Patients receive 2.5 mL placebo and 2.5 mL water orally. The placebo rinse is administered in the clinic on Day 1 (Cycle 1). There is an optional continuation phase within seven days following Day 1 (Cycle 1), patients will be encouraged to continue treatment with the study agent for an additional week (Cycle 2) where the patient takes the rinse at home every 4 hours. Chemotherapy is allowed during the continuation phase. Patients randomized to doxepin or placebo, they and their caregivers will continue to be blinded to the treatment.&#xD;
Patients will complete the Oral Symptoms booklet per the protocol.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>doxepin hydrochloride oral solution</intervention_name>
    <description>2.5 mL (25 mg) doxepin and 2.5 mL water administered orally</description>
    <arm_group_label>doxepin rinse</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>DLA (diphenhydramine, lidocaine and antacids) rinse</intervention_name>
    <description>5.0 mL administered orally</description>
    <arm_group_label>DLA (diphenhydramine, lidocaine and antacid) rinse</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>2.5 mL placebo and 2.5 mL water administered orally</description>
    <arm_group_label>placebo rinse</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        1. Documentation of Disease: Histologic documentation of malignancy currently undergoing&#xD;
             a course of RT (with or without chemotherapy) including the oral cavity and/or&#xD;
             oropharyngeal area to a dose of at least 4500 cGy using more than 5 fractions (i.e.,&#xD;
             stereotactic body radiation therapy [SBRT] is not allowed).&#xD;
&#xD;
          2. Physical exam demonstrating evidence of radiotherapy-related mucositis in the visible&#xD;
             oral cavity and/or oropharynx consistent with mucous membrane toxicity greater than 0&#xD;
             using the Acute Radiation Morbidity Scoring Criteria.&#xD;
&#xD;
          3. At least 4 (out of 10) patient-reported oral pain related to oral mucositis secondary&#xD;
             to RT for which the patient seeks relief, as measured on the Oral Pain Assessment.&#xD;
&#xD;
             Note: The pain score must be at least 4 at the time that the patient starts the first&#xD;
             dose of study medication. The patient may be enrolled to the study if s/he, at times,&#xD;
             has a pain score of at least 4, so long as initiation of study treatment begins when&#xD;
             the pain score is at least 4.&#xD;
&#xD;
          4. Ability to complete questionnaire(s) by themselves or with assistance.&#xD;
&#xD;
          5. No known allergy to diphenhydramine, lidocaine, antacid (aluminum hydroxide, magnesium&#xD;
             hydroxide, and simethicone), doxepin, tricyclic antidepressants, or any known&#xD;
             component of the drug formulation in the testing arms.&#xD;
&#xD;
          6. No use of any anti-arrhythmic medication (except for beta-blockers) including&#xD;
             lidocaine, linezolid, ipratropium, or medications with high anti-cholinergic potency&#xD;
             (including neostigmine, a tricyclic antidepressant or a monoamine oxidase inhibitor)&#xD;
             within 2 weeks prior to registration.&#xD;
&#xD;
          7. No current diagnosed untreated or unresolved oral candidiasis or oral HSV infection.&#xD;
&#xD;
          8. No history of untreated narrow angle glaucoma within 6 weeks prior to registration.&#xD;
&#xD;
          9. No untreated urinary retention within 6 weeks prior to registration.&#xD;
&#xD;
         10. No current use of glutamine or sucralfate powders at the time of registration (no&#xD;
             washout required).&#xD;
&#xD;
         11. No cryotherapy for prophylactic mucosal protection within 6 weeks prior to&#xD;
             registration.&#xD;
&#xD;
         12. Not pregnant, because patients eligible for this study will be receiving radiotherapy,&#xD;
             which has known genotoxic, mutagenic and teratogenic effects. Therefore, for women of&#xD;
             childbearing potential only, a negative pregnancy test done ≤ 28 days prior to&#xD;
             registration is required.&#xD;
&#xD;
         13. Age ≥ 18 years&#xD;
&#xD;
         14. ECOG Performance Status 0, 1, or 2&#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>Robert Miller, MD, MS</last_name>
    <role>Study Chair</role>
    <affiliation>Mayo Clinic</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Anchorage Radiation Therapy Center</name>
      <address>
        <city>Anchorage</city>
        <state>Alaska</state>
        <zip>99504</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alaska Breast Care and Surgery LLC</name>
      <address>
        <city>Anchorage</city>
        <state>Alaska</state>
        <zip>99508</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alaska Oncology and Hematology LLC</name>
      <address>
        <city>Anchorage</city>
        <state>Alaska</state>
        <zip>99508</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alaska Regional Hospital</name>
      <address>
        <city>Anchorage</city>
        <state>Alaska</state>
        <zip>99508</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alaska Women's Cancer Care</name>
      <address>
        <city>Anchorage</city>
        <state>Alaska</state>
        <zip>99508</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Anchorage Oncology Centre</name>
      <address>
        <city>Anchorage</city>
        <state>Alaska</state>
        <zip>99508</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Katmai Oncology Group</name>
      <address>
        <city>Anchorage</city>
        <state>Alaska</state>
        <zip>99508</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Providence Alaska Medical Center</name>
      <address>
        <city>Anchorage</city>
        <state>Alaska</state>
        <zip>99508</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Providence Saint Joseph Medical Center/Disney Family Cancer Center</name>
      <address>
        <city>Burbank</city>
        <state>California</state>
        <zip>91505</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Epic Care-Dublin</name>
      <address>
        <city>Dublin</city>
        <state>California</state>
        <zip>94568</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bay Area Breast Surgeons Inc</name>
      <address>
        <city>Emeryville</city>
        <state>California</state>
        <zip>94608</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Epic Care Partners in Cancer Care</name>
      <address>
        <city>Emeryville</city>
        <state>California</state>
        <zip>94608</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Comprehensive Cancer Care and Research Institute of Colorado LLC</name>
      <address>
        <city>Englewood</city>
        <state>California</state>
        <zip>80113</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Contra Costa Regional Medical Center</name>
      <address>
        <city>Martinez</city>
        <state>California</state>
        <zip>94553-3156</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alta Bates Summit Medical Center - Summit Campus</name>
      <address>
        <city>Oakland</city>
        <state>California</state>
        <zip>94609</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bay Area Tumor Institute CCOP</name>
      <address>
        <city>Oakland</city>
        <state>California</state>
        <zip>94609</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hematology and Oncology Associates-Oakland</name>
      <address>
        <city>Oakland</city>
        <state>California</state>
        <zip>94609</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rocky Mountain Cancer Centers-Aurora</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80012</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Medical Center of Aurora</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80012</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Boulder Community Hospital</name>
      <address>
        <city>Boulder</city>
        <state>Colorado</state>
        <zip>80301</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rocky Mountain Cancer Centers-Boulder</name>
      <address>
        <city>Boulder</city>
        <state>Colorado</state>
        <zip>80304</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Penrose-Saint Francis Healthcare</name>
      <address>
        <city>Colorado Springs</city>
        <state>Colorado</state>
        <zip>80907</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rocky Mountain Cancer Centers-Penrose</name>
      <address>
        <city>Colorado Springs</city>
        <state>Colorado</state>
        <zip>80907</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Porter Adventist Hospital</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Exempla Saint Joseph Hospital</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80218</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Presbyterian - Saint Lukes Medical Center - Health One</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80218</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rocky Mountain Cancer Centers-Midtown</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80218</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rocky Mountain Cancer Centers-Rose</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80220</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rose Medical Center</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80220</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Colorado Blood Cancer Institute</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80907</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mercy Medical Center</name>
      <address>
        <city>Durango</city>
        <state>Colorado</state>
        <zip>81301</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Southwest Oncology PC</name>
      <address>
        <city>Durango</city>
        <state>Colorado</state>
        <zip>81301</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Swedish Medical Center</name>
      <address>
        <city>Englewood</city>
        <state>Colorado</state>
        <zip>80110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mountain Blue Cancer Care Center</name>
      <address>
        <city>Golden</city>
        <state>Colorado</state>
        <zip>80401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>North Colorado Medical Center</name>
      <address>
        <city>Greeley</city>
        <state>Colorado</state>
        <zip>80631</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rocky Mountain Cancer Centers-Greenwood Village</name>
      <address>
        <city>Greenwood Village</city>
        <state>Colorado</state>
        <zip>80111</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rocky Mountain Cancer Centers-Lakewood</name>
      <address>
        <city>Lakewood</city>
        <state>Colorado</state>
        <zip>80228</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Anthony Hospital</name>
      <address>
        <city>Lakewood</city>
        <state>Colorado</state>
        <zip>80228</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rocky Mountain Cancer Centers-Littleton</name>
      <address>
        <city>Littleton</city>
        <state>Colorado</state>
        <zip>80120</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Littleton Adventist Hospital</name>
      <address>
        <city>Littleton</city>
        <state>Colorado</state>
        <zip>80122</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rocky Mountain Cancer Centers-Sky Ridge</name>
      <address>
        <city>Lone Tree</city>
        <state>Colorado</state>
        <zip>80124</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sky Ridge Medical Center</name>
      <address>
        <city>Lone Tree</city>
        <state>Colorado</state>
        <zip>80124</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Longmont United Hospital</name>
      <address>
        <city>Longmont</city>
        <state>Colorado</state>
        <zip>80501</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rocky Mountain Cancer Centers-Longmont</name>
      <address>
        <city>Longmont</city>
        <state>Colorado</state>
        <zip>80501</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>McKee Medical Center</name>
      <address>
        <city>Loveland</city>
        <state>Colorado</state>
        <zip>80539</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Parker Adventist Hospital</name>
      <address>
        <city>Parker</city>
        <state>Colorado</state>
        <zip>80138</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rocky Mountain Cancer Centers-Parker</name>
      <address>
        <city>Parker</city>
        <state>Colorado</state>
        <zip>80138</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Mary Corwin Medical Center</name>
      <address>
        <city>Pueblo</city>
        <state>Colorado</state>
        <zip>81004</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rocky Mountain Cancer Centers - Pueblo</name>
      <address>
        <city>Pueblo</city>
        <state>Colorado</state>
        <zip>81008</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rocky Mountain Cancer Centers-Thornton</name>
      <address>
        <city>Thornton</city>
        <state>Colorado</state>
        <zip>80260</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Exempla Lutheran Medical Center</name>
      <address>
        <city>Wheat Ridge</city>
        <state>Colorado</state>
        <zip>80033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Francis Hospital and Medical Center</name>
      <address>
        <city>Hartford</city>
        <state>Connecticut</state>
        <zip>06105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Middlesex Hospital</name>
      <address>
        <city>Middletown</city>
        <state>Connecticut</state>
        <zip>06457</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Veterans Affairs Medical Center - Washington, DC</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20422</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Morton Plant Hospital</name>
      <address>
        <city>Clearwater</city>
        <state>Florida</state>
        <zip>33756</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Regional Hospital/Joe DiMaggio Children's Hospital</name>
      <address>
        <city>Hollywood</city>
        <state>Florida</state>
        <zip>33021</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mount Sinai Medical Center</name>
      <address>
        <city>Miami Beach</city>
        <state>Florida</state>
        <zip>33140</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Hospital West</name>
      <address>
        <city>Pembroke Pines</city>
        <state>Florida</state>
        <zip>33028</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Joseph's Hospital/Children's Hospital-Tampa</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33607</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Alphonsus Cancer Care Center-Boise</name>
      <address>
        <city>Boise</city>
        <state>Idaho</state>
        <zip>83706</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Luke's Mountain States Tumor Institute</name>
      <address>
        <city>Boise</city>
        <state>Idaho</state>
        <zip>83712</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Luke's Mountain States Tumor Institute - Fruitland</name>
      <address>
        <city>Fruitland</city>
        <state>Idaho</state>
        <zip>83619</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Luke's Mountain States Tumor Institute - Meridian</name>
      <address>
        <city>Meridian</city>
        <state>Idaho</state>
        <zip>83642</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Luke's Mountain States Tumor Institute - Nampa</name>
      <address>
        <city>Nampa</city>
        <state>Idaho</state>
        <zip>83686</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Luke's Mountain States Tumor Institute-Twin Falls</name>
      <address>
        <city>Twin Falls</city>
        <state>Idaho</state>
        <zip>83301</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Illinois CancerCare - Bloomington</name>
      <address>
        <city>Bloomington</city>
        <state>Illinois</state>
        <zip>61701</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Joseph Medical Center</name>
      <address>
        <city>Bloomington</city>
        <state>Illinois</state>
        <zip>61701</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Illinois CancerCare - Canton</name>
      <address>
        <city>Canton</city>
        <state>Illinois</state>
        <zip>61520</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Hospital of Carbondale</name>
      <address>
        <city>Carbondale</city>
        <state>Illinois</state>
        <zip>62902</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centralia Oncology Clinic</name>
      <address>
        <city>Centralia</city>
        <state>Illinois</state>
        <zip>62801</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cancer Care Specialists of Central Illinois</name>
      <address>
        <city>Decatur</city>
        <state>Illinois</state>
        <zip>62526</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Decatur Memorial Hospital</name>
      <address>
        <city>Decatur</city>
        <state>Illinois</state>
        <zip>62526</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Heartland Cancer Research NCORP</name>
      <address>
        <city>Decatur</city>
        <state>Illinois</state>
        <zip>62526</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Crossroads Cancer Center</name>
      <address>
        <city>Effingham</city>
        <state>Illinois</state>
        <zip>62401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Illinois CancerCare - Eureka</name>
      <address>
        <city>Eureka</city>
        <state>Illinois</state>
        <zip>61530</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Illinois CancerCare - Galesburg</name>
      <address>
        <city>Galesburg</city>
        <state>Illinois</state>
        <zip>61401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Western Illinois Cancer Treatment Center</name>
      <address>
        <city>Galesburg</city>
        <state>Illinois</state>
        <zip>61401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Illinois CancerCare - Kewanee Clinic</name>
      <address>
        <city>Kewanee</city>
        <state>Illinois</state>
        <zip>61443</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Illinois CancerCare - Macomb</name>
      <address>
        <city>Macomb</city>
        <state>Illinois</state>
        <zip>61455</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Garneau, Stewart C MD (UIA Investigator)</name>
      <address>
        <city>Moline</city>
        <state>Illinois</state>
        <zip>61265</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Spector, David MD (UIA Investigator)</name>
      <address>
        <city>Moline</city>
        <state>Illinois</state>
        <zip>61265</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Trinity Medical Center</name>
      <address>
        <city>Moline</city>
        <state>Illinois</state>
        <zip>61265</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Illinois CancerCare- Ottawa Clinic</name>
      <address>
        <city>Ottawa</city>
        <state>Illinois</state>
        <zip>61350</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Radiation Oncology of Northern Illinois</name>
      <address>
        <city>Ottawa</city>
        <state>Illinois</state>
        <zip>61350</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Illinois CancerCare-Pekin</name>
      <address>
        <city>Pekin</city>
        <state>Illinois</state>
        <zip>61554</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pekin Cancer Treatment Center</name>
      <address>
        <city>Pekin</city>
        <state>Illinois</state>
        <zip>61554</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Methodist Medical Center of Illinois</name>
      <address>
        <city>Peoria</city>
        <state>Illinois</state>
        <zip>61603</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>OSF Saint Francis Medical Center Radiation Oncology Service at the Central Illinois Comprehensive CC</name>
      <address>
        <city>Peoria</city>
        <state>Illinois</state>
        <zip>61615-7827</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Illinois CancerCare-Peoria</name>
      <address>
        <city>Peoria</city>
        <state>Illinois</state>
        <zip>61615</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>OSF St. Francis Medical Center</name>
      <address>
        <city>Peoria</city>
        <state>Illinois</state>
        <zip>61637</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Illinois CancerCare-Peru</name>
      <address>
        <city>Peru</city>
        <state>Illinois</state>
        <zip>61354</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Valley Radiation Oncology</name>
      <address>
        <city>Peru</city>
        <state>Illinois</state>
        <zip>61354</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Illinois CancerCare-Princeton</name>
      <address>
        <city>Princeton</city>
        <state>Illinois</state>
        <zip>61356</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>OSF Saint Anthony Medical Center</name>
      <address>
        <city>Rockford</city>
        <state>Illinois</state>
        <zip>61108</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Central Illinois Hematology Oncology Center</name>
      <address>
        <city>Springfield</city>
        <state>Illinois</state>
        <zip>62702</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Springfield Clinic</name>
      <address>
        <city>Springfield</city>
        <state>Illinois</state>
        <zip>62703</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Medical Center</name>
      <address>
        <city>Springfield</city>
        <state>Illinois</state>
        <zip>62781-0001</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cancer Care Specialists of Illinois-Swansea</name>
      <address>
        <city>Swansea</city>
        <state>Illinois</state>
        <zip>62226</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Regional Cancer Center Day Road</name>
      <address>
        <city>Mishawaka</city>
        <state>Indiana</state>
        <zip>46544</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Hospital of South Bend</name>
      <address>
        <city>South Bend</city>
        <state>Indiana</state>
        <zip>46601</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Constantinou, Costas L MD (UIA Investigator)</name>
      <address>
        <city>Bettendorf</city>
        <state>Iowa</state>
        <zip>52722</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mercy Hospital</name>
      <address>
        <city>Cedar Rapids</city>
        <state>Iowa</state>
        <zip>52403</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oncology Associates at Mercy Medical Center</name>
      <address>
        <city>Cedar Rapids</city>
        <state>Iowa</state>
        <zip>52403</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Iowa Methodist Medical Center</name>
      <address>
        <city>Des Moines</city>
        <state>Iowa</state>
        <zip>50309</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical Oncology and Hematology Associates - Des Moines</name>
      <address>
        <city>Des Moines</city>
        <state>Iowa</state>
        <zip>50309</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Iowa Lutheran Hospital</name>
      <address>
        <city>Des Moines</city>
        <state>Iowa</state>
        <zip>50316</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Siouxland Regional Cancer Center</name>
      <address>
        <city>Sioux City</city>
        <state>Iowa</state>
        <zip>51101</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Methodist West Hospital</name>
      <address>
        <city>West Des Moines</city>
        <state>Iowa</state>
        <zip>50266</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cancer Center of Kansas - Chanute</name>
      <address>
        <city>Chanute</city>
        <state>Kansas</state>
        <zip>66720</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cancer Center of Kansas - Dodge City</name>
      <address>
        <city>Dodge City</city>
        <state>Kansas</state>
        <zip>67801</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cancer Center of Kansas - El Dorado</name>
      <address>
        <city>El Dorado</city>
        <state>Kansas</state>
        <zip>67042</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cancer Center of Kansas - Fort Scott</name>
      <address>
        <city>Fort Scott</city>
        <state>Kansas</state>
        <zip>66701</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cancer Center of Kansas - Independence</name>
      <address>
        <city>Independence</city>
        <state>Kansas</state>
        <zip>67301</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cancer Center of Kansas - Kingman</name>
      <address>
        <city>Kingman</city>
        <state>Kansas</state>
        <zip>67068</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lawrence Memorial Hospital</name>
      <address>
        <city>Lawrence</city>
        <state>Kansas</state>
        <zip>66044</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cancer Center of Kansas - Liberal</name>
      <address>
        <city>Liberal</city>
        <state>Kansas</state>
        <zip>67901</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cancer Center of Kansas - Newton</name>
      <address>
        <city>Newton</city>
        <state>Kansas</state>
        <zip>67114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cancer Center of Kansas - Parsons</name>
      <address>
        <city>Parsons</city>
        <state>Kansas</state>
        <zip>67357</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cancer Center of Kansas - Pratt</name>
      <address>
        <city>Pratt</city>
        <state>Kansas</state>
        <zip>67124</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cancer Center of Kansas - Salina</name>
      <address>
        <city>Salina</city>
        <state>Kansas</state>
        <zip>67401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cancer Center of Kansas - Wellington</name>
      <address>
        <city>Wellington</city>
        <state>Kansas</state>
        <zip>67152</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Associates In Womens Health</name>
      <address>
        <city>Wichita</city>
        <state>Kansas</state>
        <zip>67208</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cancer Center of Kansas - Wichita Medical Arts Tower</name>
      <address>
        <city>Wichita</city>
        <state>Kansas</state>
        <zip>67208</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cancer Center of Kansas - Main Office</name>
      <address>
        <city>Wichita</city>
        <state>Kansas</state>
        <zip>67214</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Via Christi Regional Medical Center</name>
      <address>
        <city>Wichita</city>
        <state>Kansas</state>
        <zip>67214</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wesley Medical Center</name>
      <address>
        <city>Wichita</city>
        <state>Kansas</state>
        <zip>67214</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cancer Center of Kansas - Winfield</name>
      <address>
        <city>Winfield</city>
        <state>Kansas</state>
        <zip>67156</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Maine Medical Center - Bramhall Campus</name>
      <address>
        <city>Portland</city>
        <state>Maine</state>
        <zip>04102</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Joseph Mercy Hospital</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bronson Battle Creek</name>
      <address>
        <city>Battle Creek</city>
        <state>Michigan</state>
        <zip>49017</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oakwood Hospital and Medical Center</name>
      <address>
        <city>Dearborn</city>
        <state>Michigan</state>
        <zip>48124</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint John Hospital and Medical Center</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48236</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Green Bay Oncology - Escanaba</name>
      <address>
        <city>Escanaba</city>
        <state>Michigan</state>
        <zip>49431</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Genesys Hurley Cancer Institute</name>
      <address>
        <city>Flint</city>
        <state>Michigan</state>
        <zip>48503</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hurley Medical Center</name>
      <address>
        <city>Flint</city>
        <state>Michigan</state>
        <zip>48503</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mercy Health Saint Mary's</name>
      <address>
        <city>Grand Rapids</city>
        <state>Michigan</state>
        <zip>49503</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Spectrum Health at Butterworth Campus</name>
      <address>
        <city>Grand Rapids</city>
        <state>Michigan</state>
        <zip>49503</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Green Bay Oncology - Iron Mountain</name>
      <address>
        <city>Iron Mountain</city>
        <state>Michigan</state>
        <zip>49801</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Allegiance Health</name>
      <address>
        <city>Jackson</city>
        <state>Michigan</state>
        <zip>49201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Borgess Medical Center</name>
      <address>
        <city>Kalamazoo</city>
        <state>Michigan</state>
        <zip>49001</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>West Michigan Cancer Center</name>
      <address>
        <city>Kalamazoo</city>
        <state>Michigan</state>
        <zip>49007-3731</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bronson Methodist Hospital</name>
      <address>
        <city>Kalamazoo</city>
        <state>Michigan</state>
        <zip>49007</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sparrow Hospital</name>
      <address>
        <city>Lansing</city>
        <state>Michigan</state>
        <zip>48912</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Mary Mercy Hospital</name>
      <address>
        <city>Livonia</city>
        <state>Michigan</state>
        <zip>48154</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mercy Health Mercy Campus</name>
      <address>
        <city>Muskegon</city>
        <state>Michigan</state>
        <zip>49444</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lakeland Community Hospital</name>
      <address>
        <city>Niles</city>
        <state>Michigan</state>
        <zip>49120</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Joseph Mercy Oakland</name>
      <address>
        <city>Pontiac</city>
        <state>Michigan</state>
        <zip>48341</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Joseph Mercy Port Huron</name>
      <address>
        <city>Port Huron</city>
        <state>Michigan</state>
        <zip>48060</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Spectrum Health Reed City Hospital</name>
      <address>
        <city>Reed City</city>
        <state>Michigan</state>
        <zip>49677</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>William Beaumont Hospital - Royal Oak</name>
      <address>
        <city>Royal Oak</city>
        <state>Michigan</state>
        <zip>48073</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Mary's of Michigan</name>
      <address>
        <city>Saginaw</city>
        <state>Michigan</state>
        <zip>48601</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lakeland Hospital</name>
      <address>
        <city>Saint Joseph</city>
        <state>Michigan</state>
        <zip>49085</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Marie Yeager Cancer Center</name>
      <address>
        <city>Saint Joseph</city>
        <state>Michigan</state>
        <zip>49085</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Munson Medical Center</name>
      <address>
        <city>Traverse City</city>
        <state>Michigan</state>
        <zip>49684</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>William Beaumont Hospital - Troy</name>
      <address>
        <city>Troy</city>
        <state>Michigan</state>
        <zip>48098</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint John Macomb-Oakland Hospital</name>
      <address>
        <city>Warren</city>
        <state>Michigan</state>
        <zip>48093</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sanford Clinic North-Bemidji</name>
      <address>
        <city>Bemidji</city>
        <state>Minnesota</state>
        <zip>56601</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fairview Ridges Hospital</name>
      <address>
        <city>Burnsville</city>
        <state>Minnesota</state>
        <zip>55337</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mercy Hospital</name>
      <address>
        <city>Coon Rapids</city>
        <state>Minnesota</state>
        <zip>55433</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fairview Southdale Hospital</name>
      <address>
        <city>Edina</city>
        <state>Minnesota</state>
        <zip>55435</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Unity Hospital</name>
      <address>
        <city>Fridley</city>
        <state>Minnesota</state>
        <zip>55432</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hutchinson Area Health Care</name>
      <address>
        <city>Hutchinson</city>
        <state>Minnesota</state>
        <zip>55350</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Minnesota Oncology Hematology PA-Maplewood</name>
      <address>
        <city>Maplewood</city>
        <state>Minnesota</state>
        <zip>55109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint John's Hospital - Healtheast</name>
      <address>
        <city>Maplewood</city>
        <state>Minnesota</state>
        <zip>55109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Abbott-Northwestern Hospital</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55407</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hennepin County Medical Center</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55415</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Health Partners Inc</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55454</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>New Ulm Medical Center</name>
      <address>
        <city>New Ulm</city>
        <state>Minnesota</state>
        <zip>56073</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>North Memorial Medical Health Center</name>
      <address>
        <city>Robbinsdale</city>
        <state>Minnesota</state>
        <zip>55422</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Park Nicollet Clinic - Saint Louis Park</name>
      <address>
        <city>Saint Louis Park</city>
        <state>Minnesota</state>
        <zip>55416</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Regions Hospital</name>
      <address>
        <city>Saint Paul</city>
        <state>Minnesota</state>
        <zip>55101</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>United Hospital</name>
      <address>
        <city>Saint Paul</city>
        <state>Minnesota</state>
        <zip>55102</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Francis Regional Medical Center</name>
      <address>
        <city>Shakopee</city>
        <state>Minnesota</state>
        <zip>55379</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lakeview Hospital</name>
      <address>
        <city>Stillwater</city>
        <state>Minnesota</state>
        <zip>55082</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ridgeview Medical Center</name>
      <address>
        <city>Waconia</city>
        <state>Minnesota</state>
        <zip>55387</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rice Memorial Hospital</name>
      <address>
        <city>Willmar</city>
        <state>Minnesota</state>
        <zip>56201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Minnesota Oncology Hematology PA-Woodbury</name>
      <address>
        <city>Woodbury</city>
        <state>Minnesota</state>
        <zip>55125</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Central Care Center - Carrie J. Babb Cancer Center</name>
      <address>
        <city>Bolivar</city>
        <state>Missouri</state>
        <zip>65613</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Parkland Health Center-Bonne Terre</name>
      <address>
        <city>Bonne Terre</city>
        <state>Missouri</state>
        <zip>63628</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cox Cancer Center Branson</name>
      <address>
        <city>Branson</city>
        <state>Missouri</state>
        <zip>65616</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Francis Medical Center</name>
      <address>
        <city>Cape Girardeau</city>
        <state>Missouri</state>
        <zip>63703</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Southeast Cancer Center</name>
      <address>
        <city>Cape Girardeau</city>
        <state>Missouri</state>
        <zip>63703</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Capital Region Medical Center-Goldschmidt Cancer Center</name>
      <address>
        <city>Jefferson City</city>
        <state>Missouri</state>
        <zip>65109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mercy Clinic-Rolla-Cancer and Hematology</name>
      <address>
        <city>Rolla</city>
        <state>Missouri</state>
        <zip>65401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Phelps County Regional Medical Center</name>
      <address>
        <city>Rolla</city>
        <state>Missouri</state>
        <zip>65401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Louis Cancer and Breast Institute - South City</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington University School of Medicine</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Siteman Cancer Center-South County</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63129</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Missouri Baptist Medical Center</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63131</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Barnes-Jewish West County Hospital</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63141</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mercy Hospital Saint Louis</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63141</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sainte Genevieve County Memorial Hospital</name>
      <address>
        <city>Sainte Genevieve</city>
        <state>Missouri</state>
        <zip>63670</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cancer Research for the Ozarks NCORP</name>
      <address>
        <city>Springfield</city>
        <state>Missouri</state>
        <zip>65804</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mercy Hospital Springfield</name>
      <address>
        <city>Springfield</city>
        <state>Missouri</state>
        <zip>65804</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cox Health South Hospital</name>
      <address>
        <city>Springfield</city>
        <state>Missouri</state>
        <zip>65807</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Missouri Baptist Sullivan Hospital</name>
      <address>
        <city>Sullivan</city>
        <state>Missouri</state>
        <zip>63080</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Missouri Baptist Outpatient Center-Sunset Hills</name>
      <address>
        <city>Sunset Hills</city>
        <state>Missouri</state>
        <zip>63127</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Comprehensive Cancer Centers of Nevada - Henderson</name>
      <address>
        <city>Henderson</city>
        <state>Nevada</state>
        <zip>89052</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Las Vegas Cancer Center-Henderson</name>
      <address>
        <city>Henderson</city>
        <state>Nevada</state>
        <zip>89052</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>21st Century Oncology-Henderson</name>
      <address>
        <city>Henderson</city>
        <state>Nevada</state>
        <zip>89074</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Comprehensive Cancer Centers of Nevada-Southeast Henderson</name>
      <address>
        <city>Henderson</city>
        <state>Nevada</state>
        <zip>89074</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Medical Center of Southern Nevada</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89102</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cancer and Blood Specialists-Henderson</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nevada Cancer Research Foundation NCORP</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Radiation Oncology Centers of Nevada Central</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>21st Century Oncology</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>HealthCare Partners Medical Group Oncology/Hematology-Maryland Parkway</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>HealthCare Partners Medical Group Oncology/Hematology-San Martin</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89113</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Radiation Oncology Centers of Nevada Southeast</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89119</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cancer Therapy and Integrative Medicine</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89121</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>21st Century Oncology-Vegas Tenaya</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89128</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cancer and Blood Specialists-Shadow</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89128</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cancer and Blood Specialists-Tenaya</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89128</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Comprehensive Cancer Centers of Nevada - Northwest</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89128</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>HealthCare Partners Medical Group Oncology/Hematology-Tenaya</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89128</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Comprehensive Cancer Centers of Nevada-Summerlin</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89144</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Las Vegas Cancer Center-Medical Center</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89148-2405</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>21st Century Oncology-Fort Apache</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89148</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cancer and Blood Specialists-Fort Apache</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89148</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>HealthCare Partners Medical Group Oncology/Hematology-Centennial Hills</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89149</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Comprehensive Cancer Centers of Nevada - Central Valley</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89169</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Comprehensive Cancer Centers of Nevada</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89169</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Veterans Affairs Western New York Health Care System-Buffalo</name>
      <address>
        <city>Buffalo</city>
        <state>New York</state>
        <zip>14215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <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>North Shore-LIJ Health System/Center for Advanced Medicine</name>
      <address>
        <city>New Hyde Park</city>
        <state>New York</state>
        <zip>11040</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Randolph Hospital</name>
      <address>
        <city>Asheboro</city>
        <state>North Carolina</state>
        <zip>27203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novant Health Presbyterian Medical Center</name>
      <address>
        <city>Charlotte</city>
        <state>North Carolina</state>
        <zip>28204</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Carolina Surgical Clinic of Charlotte PA</name>
      <address>
        <city>Charlotte</city>
        <state>North Carolina</state>
        <zip>28207</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oncology Specialists of Charlotte</name>
      <address>
        <city>Charlotte</city>
        <state>North Carolina</state>
        <zip>28207</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Southern Oncology Specialists-Charlotte</name>
      <address>
        <city>Charlotte</city>
        <state>North Carolina</state>
        <zip>28262</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Southeastern Medical Oncology Center-Clinton</name>
      <address>
        <city>Clinton</city>
        <state>North Carolina</state>
        <zip>28328</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CaroMont Regional Medical Center</name>
      <address>
        <city>Gastonia</city>
        <state>North Carolina</state>
        <zip>28054</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Southeastern Medical Oncology Center-Goldsboro</name>
      <address>
        <city>Goldsboro</city>
        <state>North Carolina</state>
        <zip>27534</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wayne Memorial Hospital</name>
      <address>
        <city>Goldsboro</city>
        <state>North Carolina</state>
        <zip>27534</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cone Health Cancer Center</name>
      <address>
        <city>Greensboro</city>
        <state>North Carolina</state>
        <zip>27403</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hendersonville Hematology and Oncology at Pardee</name>
      <address>
        <city>Hendersonville</city>
        <state>North Carolina</state>
        <zip>28739</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Margaret R Pardee Memorial Hospital</name>
      <address>
        <city>Hendersonville</city>
        <state>North Carolina</state>
        <zip>28791</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lake Norman Hematology Oncology Specialists-Huntersville</name>
      <address>
        <city>Huntersville</city>
        <state>North Carolina</state>
        <zip>28078</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Southern Oncology Specialists-Huntersville</name>
      <address>
        <city>Huntersville</city>
        <state>North Carolina</state>
        <zip>28078</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lake Norman Hematology Oncology Specialists-Huntersville</name>
      <address>
        <city>Huntersville</city>
        <state>North Carolina</state>
        <zip>287078</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Southeastern Medical Oncology Center-Jacksonville</name>
      <address>
        <city>Jacksonville</city>
        <state>North Carolina</state>
        <zip>28546</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novant Health Oncology Specialists-Kernersville</name>
      <address>
        <city>Kernersville</city>
        <state>North Carolina</state>
        <zip>27284</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novant Health Oncology Specialists-Davidson County</name>
      <address>
        <city>Lexington</city>
        <state>North Carolina</state>
        <zip>27295</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Matthews Radiation Oncology Center</name>
      <address>
        <city>Matthews</city>
        <state>North Carolina</state>
        <zip>28105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novant Health Cancer Specialists-Matthews</name>
      <address>
        <city>Matthews</city>
        <state>North Carolina</state>
        <zip>28105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lake Norman Hematology Oncology Specialists-Mooresville</name>
      <address>
        <city>Mooresville</city>
        <state>North Carolina</state>
        <zip>28117</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novant Health Oncology Specialists-Mount Airy</name>
      <address>
        <city>Mount Airy</city>
        <state>North Carolina</state>
        <zip>27030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>FirstHealth of the Carolinas-Moore Regional Hospital</name>
      <address>
        <city>Pinehurst</city>
        <state>North Carolina</state>
        <zip>28374</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Annie Penn Memorial Hospital</name>
      <address>
        <city>Reidsville</city>
        <state>North Carolina</state>
        <zip>27320</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Carolina Oncology Associates PA</name>
      <address>
        <city>Salisbury</city>
        <state>North Carolina</state>
        <zip>28144</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novant Health Oncology Specialists-Statesville</name>
      <address>
        <city>Statesville</city>
        <state>North Carolina</state>
        <zip>28625</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novant Health Oncology Specialists-Wilkesboro</name>
      <address>
        <city>Wilkesboro</city>
        <state>North Carolina</state>
        <zip>28659</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Southeastern Medical Oncology Center-Wilson</name>
      <address>
        <city>Wilson</city>
        <state>North Carolina</state>
        <zip>27893</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novant Health Forsyth Medical Center</name>
      <address>
        <city>Winston-Salem</city>
        <state>North Carolina</state>
        <zip>27103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novant Health Oncology Specialists</name>
      <address>
        <city>Winston-Salem</city>
        <state>North Carolina</state>
        <zip>27103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Winston-Salem Health Care</name>
      <address>
        <city>Winston-Salem</city>
        <state>North Carolina</state>
        <zip>27103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sanford Bismarck Medical Center</name>
      <address>
        <city>Bismarck</city>
        <state>North Dakota</state>
        <zip>58501</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sanford Clinic North-Fargo</name>
      <address>
        <city>Fargo</city>
        <state>North Dakota</state>
        <zip>58102</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sanford Medical Center-Fargo</name>
      <address>
        <city>Fargo</city>
        <state>North Dakota</state>
        <zip>58122</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sanford Roger Maris Cancer Center</name>
      <address>
        <city>Fargo</city>
        <state>North Dakota</state>
        <zip>58122</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Altru Cancer Center</name>
      <address>
        <city>Grand Forks</city>
        <state>North Dakota</state>
        <zip>58201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mercy Hospital Oklahoma City</name>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <zip>73120</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Charles Health System</name>
      <address>
        <city>Bend</city>
        <state>Oregon</state>
        <zip>97701</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clackamas Radiation Oncology Center</name>
      <address>
        <city>Clackamas</city>
        <state>Oregon</state>
        <zip>97015</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Providence Oncology and Hematology Care Southeast</name>
      <address>
        <city>Clackamas</city>
        <state>Oregon</state>
        <zip>97015</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bay Area Hospital</name>
      <address>
        <city>Coos Bay</city>
        <state>Oregon</state>
        <zip>97420</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Providence Newberg Medical Center</name>
      <address>
        <city>Newberg</city>
        <state>Oregon</state>
        <zip>97132</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Providence Willamette Falls Medical Center</name>
      <address>
        <city>Oregon City</city>
        <state>Oregon</state>
        <zip>97045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Providence Portland Medical Center</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Providence Saint Vincent Medical Center</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97225</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Geisinger Medical Center</name>
      <address>
        <city>Danville</city>
        <state>Pennsylvania</state>
        <zip>17822</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Adams Cancer Center</name>
      <address>
        <city>Gettysburg</city>
        <state>Pennsylvania</state>
        <zip>17325</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Geisinger Medical Center-Cancer Center Hazelton</name>
      <address>
        <city>Hazleton</city>
        <state>Pennsylvania</state>
        <zip>18201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lewistown Hospital</name>
      <address>
        <city>Lewistown</city>
        <state>Pennsylvania</state>
        <zip>17044</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Geisinger Medical Oncology-Pottsville</name>
      <address>
        <city>Pottsville</city>
        <state>Pennsylvania</state>
        <zip>17901</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Geisinger Medical Group</name>
      <address>
        <city>State College</city>
        <state>Pennsylvania</state>
        <zip>16801</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Geisinger Wyoming Valley/Henry Cancer Center</name>
      <address>
        <city>Wilkes-Barre</city>
        <state>Pennsylvania</state>
        <zip>18711</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>WellSpan Health-York Hospital</name>
      <address>
        <city>York</city>
        <state>Pennsylvania</state>
        <zip>17405</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AnMed Health Cancer Center</name>
      <address>
        <city>Anderson</city>
        <state>South Carolina</state>
        <zip>29621</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Beaufort Memorial Hospital</name>
      <address>
        <city>Beaufort</city>
        <state>South Carolina</state>
        <zip>29902</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Greenville Health System Cancer Institute-Easley</name>
      <address>
        <city>Easley</city>
        <state>South Carolina</state>
        <zip>29640</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gibbs Cancer Center-Gaffney</name>
      <address>
        <city>Gaffney</city>
        <state>South Carolina</state>
        <zip>29341</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Greenville Health System Cancer Institute - Butternut</name>
      <address>
        <city>Greenville</city>
        <state>South Carolina</state>
        <zip>29605</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Greenville Health System Cancer Institute-Andrews</name>
      <address>
        <city>Greenville</city>
        <state>South Carolina</state>
        <zip>29605</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Greenville Health System Cancer Institute-Faris</name>
      <address>
        <city>Greenville</city>
        <state>South Carolina</state>
        <zip>29605</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Greenville Memorial Hospital</name>
      <address>
        <city>Greenville</city>
        <state>South Carolina</state>
        <zip>29605</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Greenville Health System Cancer Institute-Eastside</name>
      <address>
        <city>Greenville</city>
        <state>South Carolina</state>
        <zip>29615</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Greenville Health System Cancer Institute-Greer</name>
      <address>
        <city>Greer</city>
        <state>South Carolina</state>
        <zip>29650</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gibbs Cancer Center-Pelham</name>
      <address>
        <city>Greer</city>
        <state>South Carolina</state>
        <zip>29651</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Greenville Health System Cancer Institute-Seneca</name>
      <address>
        <city>Seneca</city>
        <state>South Carolina</state>
        <zip>29672</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Spartanburg Medical Center</name>
      <address>
        <city>Spartanburg</city>
        <state>South Carolina</state>
        <zip>29303</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Greenville Health System Cancer Institute-Spartanburg</name>
      <address>
        <city>Spartanburg</city>
        <state>South Carolina</state>
        <zip>29307</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Avera Saint Luke's Hospital and Cancer Center</name>
      <address>
        <city>Aberdeen</city>
        <state>South Dakota</state>
        <zip>57401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sanford Cancer Center Oncology Clinic</name>
      <address>
        <city>Sioux Falls</city>
        <state>South Dakota</state>
        <zip>57104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Avera Cancer Institute</name>
      <address>
        <city>Sioux Falls</city>
        <state>South Dakota</state>
        <zip>57105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sanford USD Medical Center - Sioux Falls</name>
      <address>
        <city>Sioux Falls</city>
        <state>South Dakota</state>
        <zip>57117</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Martha Jefferson Hospital</name>
      <address>
        <city>Charlottesville</city>
        <state>Virginia</state>
        <zip>22901</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Providence Regional Cancer System-Aberdeen</name>
      <address>
        <city>Aberdeen</city>
        <state>Washington</state>
        <zip>98520</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cancer Care Center at Island Hospital</name>
      <address>
        <city>Anacortes</city>
        <state>Washington</state>
        <zip>98221</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Swedish Cancer Institute-Eastside Oncology Hematology</name>
      <address>
        <city>Bellevue</city>
        <state>Washington</state>
        <zip>98005</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>PeaceHealth Saint Joseph Medical Center</name>
      <address>
        <city>Bellingham</city>
        <state>Washington</state>
        <zip>98225</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Providence Regional Cancer System-Centralia</name>
      <address>
        <city>Centralia</city>
        <state>Washington</state>
        <zip>98531</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Swedish Medical Center-Edmonds</name>
      <address>
        <city>Edmonds</city>
        <state>Washington</state>
        <zip>98026</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Providence Regional Cancer Partnership</name>
      <address>
        <city>Everett</city>
        <state>Washington</state>
        <zip>98201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Swedish Medical Center - Issaquah</name>
      <address>
        <city>Issaquah</city>
        <state>Washington</state>
        <zip>98029</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Providence Regional Cancer System-Lacey</name>
      <address>
        <city>Lacey</city>
        <state>Washington</state>
        <zip>98503</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint John Medical Center</name>
      <address>
        <city>Longview</city>
        <state>Washington</state>
        <zip>98632</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Minor and James Medical PLLC</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pacific Gynecology Specialists</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Swedish Medical Center-Ballard Campus</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98107</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Group Health Cooperative-Seattle</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Swedish Medical Center-First Hill</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98122</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Providence Regional Cancer System-Shelton</name>
      <address>
        <city>Shelton</city>
        <state>Washington</state>
        <zip>98548</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rockwood Clinic Cancer Treatment Center-Valley</name>
      <address>
        <city>Spokane Valley</city>
        <state>Washington</state>
        <zip>99216</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rockwood Cancer Treatment Center-DHEC-Downtown</name>
      <address>
        <city>Spokane</city>
        <state>Washington</state>
        <zip>99204</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Evergreen Hematology and Oncology PS</name>
      <address>
        <city>Spokane</city>
        <state>Washington</state>
        <zip>99218</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>PeaceHealth Southwest Medical Center</name>
      <address>
        <city>Vancouver</city>
        <state>Washington</state>
        <zip>98664</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Providence Saint Mary Regional Cancer Center</name>
      <address>
        <city>Walla Walla</city>
        <state>Washington</state>
        <zip>99362</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>North Star Lodge Cancer Center at Yakima Valley Memorial Hospital</name>
      <address>
        <city>Yakima</city>
        <state>Washington</state>
        <zip>98902</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Providence Regional Cancer System-Yelm</name>
      <address>
        <city>Yelm</city>
        <state>Washington</state>
        <zip>98597</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Marshfield Clinic-Chippewa Center</name>
      <address>
        <city>Chippewa Falls</city>
        <state>Wisconsin</state>
        <zip>54729</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Marshfield Clinic Cancer Center at Sacred Heart</name>
      <address>
        <city>Eau Claire</city>
        <state>Wisconsin</state>
        <zip>54701</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sacred Heart Hospital</name>
      <address>
        <city>Eau Claire</city>
        <state>Wisconsin</state>
        <zip>54701</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Agnes Hospital/Agnesian Cancer Center</name>
      <address>
        <city>Fond Du Lac</city>
        <state>Wisconsin</state>
        <zip>54935</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Green Bay Oncology at Saint Vincent Hospital</name>
      <address>
        <city>Green Bay</city>
        <state>Wisconsin</state>
        <zip>54301</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Vincent Hospital</name>
      <address>
        <city>Green Bay</city>
        <state>Wisconsin</state>
        <zip>54301</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Green Bay Oncology Limited at Saint Mary's Hospital</name>
      <address>
        <city>Green Bay</city>
        <state>Wisconsin</state>
        <zip>54303</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Mary's Hospital</name>
      <address>
        <city>Green Bay</city>
        <state>Wisconsin</state>
        <zip>54303</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic Health System-Franciscan Healthcare</name>
      <address>
        <city>La Crosse</city>
        <state>Wisconsin</state>
        <zip>54601</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Holy Family Memorial Hospital</name>
      <address>
        <city>Manitowoc</city>
        <state>Wisconsin</state>
        <zip>54221</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bay Area Medical Center</name>
      <address>
        <city>Marinette</city>
        <state>Wisconsin</state>
        <zip>54143</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Marshfield Clinic</name>
      <address>
        <city>Marshfield</city>
        <state>Wisconsin</state>
        <zip>54449</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Joseph's Hospital</name>
      <address>
        <city>Marshfield</city>
        <state>Wisconsin</state>
        <zip>54449</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Marshfield Clinic-Minocqua Center</name>
      <address>
        <city>Minocqua</city>
        <state>Wisconsin</state>
        <zip>54548</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Westfields Hospital/Cancer Center of Western Wisconsin</name>
      <address>
        <city>New Richmond</city>
        <state>Wisconsin</state>
        <zip>54017</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Green Bay Oncology - Oconto Falls</name>
      <address>
        <city>Oconto Falls</city>
        <state>Wisconsin</state>
        <zip>54154</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Marshfield Clinic at James Beck Cancer Center</name>
      <address>
        <city>Rhinelander</city>
        <state>Wisconsin</state>
        <zip>54501</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Marshfield Clinic-Rice Lake Center</name>
      <address>
        <city>Rice Lake</city>
        <state>Wisconsin</state>
        <zip>54868</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Nicholas Hospital</name>
      <address>
        <city>Sheboygan</city>
        <state>Wisconsin</state>
        <zip>53081</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Marshfield Clinic at Saint Michael's Hospital</name>
      <address>
        <city>Stevens Point</city>
        <state>Wisconsin</state>
        <zip>54481</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Michael's Hospital</name>
      <address>
        <city>Stevens Point</city>
        <state>Wisconsin</state>
        <zip>54481</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Door County Cancer Center</name>
      <address>
        <city>Sturgeon Bay</city>
        <state>Wisconsin</state>
        <zip>54235-1495</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Green Bay Oncology - Sturgeon Bay</name>
      <address>
        <city>Sturgeon Bay</city>
        <state>Wisconsin</state>
        <zip>54235</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Marshfield Clinic-Wausau Center</name>
      <address>
        <city>Wausau</city>
        <state>Wisconsin</state>
        <zip>54401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Diagnostic and Treatment Center</name>
      <address>
        <city>Weston</city>
        <state>Wisconsin</state>
        <zip>54476</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Marshfield Clinic - Weston Center</name>
      <address>
        <city>Weston</city>
        <state>Wisconsin</state>
        <zip>54476</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Clare's Hospital</name>
      <address>
        <city>Weston</city>
        <state>Wisconsin</state>
        <zip>54476</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Marshfield Clinic - Wisconsin Rapids Center</name>
      <address>
        <city>Wisconsin Rapids</city>
        <state>Wisconsin</state>
        <zip>54494</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cheyenne Regional Medical Center-West</name>
      <address>
        <city>Cheyenne</city>
        <state>Wyoming</state>
        <zip>82001</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2019</verification_date>
  <study_first_submitted>August 29, 2014</study_first_submitted>
  <study_first_submitted_qc>August 29, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 1, 2014</study_first_posted>
  <results_first_submitted>December 7, 2016</results_first_submitted>
  <results_first_submitted_qc>February 27, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">April 10, 2017</results_first_posted>
  <last_update_submitted>October 4, 2019</last_update_submitted>
  <last_update_submitted_qc>October 4, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">October 16, 2019</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>Mucositis</mesh_term>
    <mesh_term>Stomatitis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diphenhydramine</mesh_term>
    <mesh_term>Promethazine</mesh_term>
    <mesh_term>Lidocaine</mesh_term>
    <mesh_term>Doxepin</mesh_term>
    <mesh_term>Antacids</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Two-hundred and seventy-five participants (92 Doxepin, 91 DLA and 92 Placebo) were enrolled between November 2014 to May 2016. Data as of 6/1/2016 was summarized for abstract submission, was reported.</recruitment_details>
      <pre_assignment_details>Total of 47 participants were excluded from all analyses due to 23 cancellations, 18 with mouth pain score&lt;4 prior to treatment, 4 with data being queried at the time of report, 1 with quality of life data non-compliance and 1 with randomization problem.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Doxepin</title>
          <description>Patients receive 2.5 mL (25 mg) doxepin and 2.5 mL water orally in the clinic on Day 1 (Cycle 1). Patients will be encouraged to continue treatment with the study agent for an additional week (Cycle 2).</description>
        </group>
        <group group_id="P2">
          <title>DLA (Diphenhydramine, Lidocaine and Antacid)</title>
          <description>Patients receive 5.0 mL DLA orally in the clinic on Day 1 (Cycle 1). Patients will be encouraged to continue treatment with the study agent for an additional week (Cycle 2).</description>
        </group>
        <group group_id="P3">
          <title>Placebo</title>
          <description>Patients receive 2.5 mL placebo and 2.5 mL water orally in the clinic on Day 1 (Cycle 1). Patients will be encouraged to continue treatment with the study agent for an additional week (Cycle 2).</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Cycle 1 (Treatment Per Protocol)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="77"/>
                <participants group_id="P2" count="76"/>
                <participants group_id="P3" count="75"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="74"/>
                <participants group_id="P2" count="71"/>
                <participants group_id="P3" count="72"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="5"/>
                <participants group_id="P3" count="3"/>
              </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 group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Alternate Therapy</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Medical Problems</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Data being queried at the time of report</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="4"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Cycle 2 (Optional Continuation Phase)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="35"/>
                <participants group_id="P2" count="36"/>
                <participants group_id="P3" count="32"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="26"/>
                <participants group_id="P2" count="29"/>
                <participants group_id="P3" count="22"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
                <participants group_id="P2" count="7"/>
                <participants group_id="P3" count="10"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="5"/>
                <participants group_id="P3" count="6"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Alternative Therapy</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other Unknown Reason</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Data being queried at the time of report</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>All participants who met eligibility criteria, had mouth pain score of at least 4 on 0 to 10 scale with higher scores indicated worst pain and started the treatment.</population>
      <group_list>
        <group group_id="B1">
          <title>Doxepin</title>
          <description>Patients receive 2.5 mL (25 mg) doxepin and 2.5 mL water orally in the clinic on Day 1 (Cycle 1). Patients will be encouraged to continue treatment with the study agent for an additional week (Cycle 2).</description>
        </group>
        <group group_id="B2">
          <title>DLA (Diphenhydramine, Lidocaine and Antacid)</title>
          <description>Patients receive 5.0 mL DLA orally in the clinic on Day 1 (Cycle 1). Patients will be encouraged to continue treatment with the study agent for an additional week (Cycle 2).</description>
        </group>
        <group group_id="B3">
          <title>Placebo</title>
          <description>Patients receive 2.5 mL placebo and 2.5 mL water orally in the clinic on Day 1 (Cycle 1). Patients will be encouraged to continue treatment with the study agent for an additional week (Cycle 2).</description>
        </group>
        <group group_id="B4">
          <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="77"/>
            <count group_id="B2" value="76"/>
            <count group_id="B3" value="75"/>
            <count group_id="B4" value="228"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="62" lower_limit="26" upper_limit="87"/>
                    <measurement group_id="B2" value="60" lower_limit="23" upper_limit="82"/>
                    <measurement group_id="B3" value="60" lower_limit="31" upper_limit="94"/>
                    <measurement group_id="B4" value="60" lower_limit="23" upper_limit="94"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;60 years old</title>
                  <measurement_list>
                    <measurement group_id="B1" value="33"/>
                    <measurement group_id="B2" value="33"/>
                    <measurement group_id="B3" value="37"/>
                    <measurement group_id="B4" value="103"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=60 years old</title>
                  <measurement_list>
                    <measurement group_id="B1" value="44"/>
                    <measurement group_id="B2" value="43"/>
                    <measurement group_id="B3" value="38"/>
                    <measurement group_id="B4" value="125"/>
                  </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="17"/>
                    <measurement group_id="B2" value="18"/>
                    <measurement group_id="B3" value="18"/>
                    <measurement group_id="B4" value="53"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="60"/>
                    <measurement group_id="B2" value="58"/>
                    <measurement group_id="B3" value="57"/>
                    <measurement group_id="B4" value="175"/>
                  </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 group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="3"/>
                  </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 group_id="B4" 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="7"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="14"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="73"/>
                    <measurement group_id="B2" value="67"/>
                    <measurement group_id="B3" value="70"/>
                    <measurement group_id="B4" value="210"/>
                  </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 group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="77"/>
                    <measurement group_id="B2" value="76"/>
                    <measurement group_id="B3" value="75"/>
                    <measurement group_id="B4" value="228"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Eastern Cooperative Oncology Group (ECOG) Performance Status</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>0=Asymptomatic and fully active</title>
                  <measurement_list>
                    <measurement group_id="B1" value="36"/>
                    <measurement group_id="B2" value="31"/>
                    <measurement group_id="B3" value="32"/>
                    <measurement group_id="B4" value="99"/>
                  </measurement_list>
                </category>
                <category>
                  <title>1=Symptomatic and fully ambulatory</title>
                  <measurement_list>
                    <measurement group_id="B1" value="40"/>
                    <measurement group_id="B2" value="39"/>
                    <measurement group_id="B3" value="40"/>
                    <measurement group_id="B4" value="119"/>
                  </measurement_list>
                </category>
                <category>
                  <title>2=Symptomatic, &lt;50% in bed during the day</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Concurrent use of chemotherapy</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Yes</title>
                  <measurement_list>
                    <measurement group_id="B1" value="61"/>
                    <measurement group_id="B2" value="62"/>
                    <measurement group_id="B3" value="62"/>
                    <measurement group_id="B4" value="185"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="13"/>
                    <measurement group_id="B4" value="43"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Mucous Membrane Grade</title>
          <description>Mucous membrane grade:&gt; 0=no change over baseline, 1=injection/may experience mild pain not requiring analgesic, 2=patchy mucositis which may produce an inflammatory serosanguinitis discharge/ may experience moderate pain requiring analgesia, 3=confluent fibrinous mucositis/ may include severe pain requiring narcotic, 4=Ulceration, hemorrhage or necrosis.</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="16"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="16"/>
                    <measurement group_id="B4" value="48"/>
                  </measurement_list>
                </category>
                <category>
                  <title>2</title>
                  <measurement_list>
                    <measurement group_id="B1" value="47"/>
                    <measurement group_id="B2" value="48"/>
                    <measurement group_id="B3" value="48"/>
                    <measurement group_id="B4" value="143"/>
                  </measurement_list>
                </category>
                <category>
                  <title>3 or more</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="11"/>
                    <measurement group_id="B4" value="37"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Mean Area Under the Curve (AUC) of Total Pain Reduction</title>
        <description>Total pain reduction (mouth and throat) was measured by the numerical analogue scale of mouth pain on a scale of 0 to 10, with 0=no pain and 10=worst pain in the questionnaires taken at baseline, and 5, 15, 30, 60, 120, 240 minutes after assigned treatment for doxepin or DLA vs. placebo. The total pain reduction was calculated by the (average of mouth and throat) area under the curve (AUC) adjusting for baseline, with time scale (baseline, 5, 15, 30, 60, 120 and 240 minutes post treatment) replaced by a numerical scale of 0, 1, 2, 3, 4, 5 and 6 respectively. The AUC was prorated when there are terminal missing data. If the missing data were intermittent, simple imputation by trapezoidal rules were applied to calculate the AUC. If a patient cancelled, was missing baseline data, or only provided baseline data, he/she was excluded from the statistical analysis.</description>
        <time_frame>Baseline, 5, 15, 30, 60, 120, 240 minutes post treatment</time_frame>
        <population>All participants who met eligibility criteria, had mouth pain score of at least 4 on 0 to 10 scale with higher scores indicated worst pain and started the treatment and had mouth and throat pain data at baseline and at least one time point beyond baseline.</population>
        <group_list>
          <group group_id="O1">
            <title>Doxepin</title>
            <description>Patients receive 2.5 mL (25 mg) doxepin and 2.5 mL water orally in the clinic on Day 1 (Cycle 1). Patients will be encouraged to continue treatment with the study agent for an additional week (Cycle 2).</description>
          </group>
          <group group_id="O2">
            <title>DLA (Diphenhydramine, Lidocaine and Antacid)</title>
            <description>Patients receive 5.0 mL DLA orally in the clinic on Day 1 (Cycle 1). Patients will be encouraged to continue treatment with the study agent for an additional week (Cycle 2).</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>Patients receive 2.5 mL placebo and 2.5 mL water orally in the clinic on Day 1 (Cycle 1). Patients will be encouraged to continue treatment with the study agent for an additional week (Cycle 2).</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Area Under the Curve (AUC) of Total Pain Reduction</title>
          <description>Total pain reduction (mouth and throat) was measured by the numerical analogue scale of mouth pain on a scale of 0 to 10, with 0=no pain and 10=worst pain in the questionnaires taken at baseline, and 5, 15, 30, 60, 120, 240 minutes after assigned treatment for doxepin or DLA vs. placebo. The total pain reduction was calculated by the (average of mouth and throat) area under the curve (AUC) adjusting for baseline, with time scale (baseline, 5, 15, 30, 60, 120 and 240 minutes post treatment) replaced by a numerical scale of 0, 1, 2, 3, 4, 5 and 6 respectively. The AUC was prorated when there are terminal missing data. If the missing data were intermittent, simple imputation by trapezoidal rules were applied to calculate the AUC. If a patient cancelled, was missing baseline data, or only provided baseline data, he/she was excluded from the statistical analysis.</description>
          <population>All participants who met eligibility criteria, had mouth pain score of at least 4 on 0 to 10 scale with higher scores indicated worst pain and started the treatment and had mouth and throat pain data at baseline and at least one time point beyond baseline.</population>
          <units>units on a scale*time 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="77"/>
                <count group_id="O2" value="76"/>
                <count group_id="O3" value="75"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.9" spread="9.7"/>
                    <measurement group_id="O2" value="11.7" spread="8.1"/>
                    <measurement group_id="O3" value="8.7" spread="10.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>0.01</p_value>
            <method>Wilcoxon rank-sum</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>0.004</p_value>
            <method>Wilcoxon rank-sum</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Total Unpleasant Taste of the Oral Rinse as Measured by the Numerical Analogue Scale of Taste of the Oral Rinse in the Questionnaires</title>
        <time_frame>Up to 4 hours post-treatment</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Total Stinging or Burning From the Oral Rinse as Measured by the Numerical Analogue Scale of Stinging or Burning From the Oral Rinse in the Questionnaires</title>
        <time_frame>Up to 4 hours post-treatment</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Total Drowsiness Increase as Measured by the Numerical Analogue Scale of Drowsiness Questionnaires</title>
        <time_frame>Up to 4 hours post-treatment every 4 hours while on treatment</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Incidence of Using Alternative Analgesics Between 1 and 4 Hours After Initial Mouthwash</title>
        <time_frame>Up to 4 hours post-treatment</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Patient Preference for Continued Therapy With Oral Rinse After Initial Test Rinse Phase, as Measured by Item 9 in the Patient-reported Questionnaire After 4 Hours</title>
        <time_frame>Up to 4 hours post-treatment</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Length of Time in the Continuation Phase</title>
        <time_frame>Up to 4 hours post-treatment</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pain Score in the Continuation Phase</title>
        <time_frame>Up to 4 hours post-treatment</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Alternative Analgesics Use in the Continuation Phase</title>
        <time_frame>Up to 4 hours post-treatment</time_frame>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>In clinic at 5, 15, 30, and 60 minutes after oral rinse and daily for up to 7 days, beginning within 1 week of Day 1.</time_frame>
      <desc>All participants who met eligibility criteria, had mouth pain score of at least 4 on 0 to 10 scale with higher scores indicated worst pain, started the treatment and had adverse events assessed during the reporting period. Adverse event data not available on one participant on Doxepin at the time of the report. Adverse events were not assessed on twenty-one participants (4 Doxepin, 5 DLA and 12 Placebo).</desc>
      <group_list>
        <group group_id="E1">
          <title>Doxepin</title>
          <description>Patients receive 2.5 mL (25 mg) doxepin and 2.5 mL water orally in the clinic on Day 1 (Cycle 1). Patients will be encouraged to continue treatment with the study agent for an additional week (Cycle 2).</description>
        </group>
        <group group_id="E2">
          <title>DLA (Diphenhydramine, Lidocaine and Antacid)</title>
          <description>Patients receive 5.0 mL DLA orally in the clinic on Day 1 (Cycle 1). Patients will be encouraged to continue treatment with the study agent for an additional week (Cycle 2).</description>
        </group>
        <group group_id="E3">
          <title>Placebo</title>
          <description>Patients receive 2.5 mL placebo and 2.5 mL water orally in the clinic on Day 1 (Cycle 1). Patients will be encouraged to continue treatment with the study agent for an additional week (Cycle 2).</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>CTCAEV4.0</default_vocab>
        <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="2" subjects_at_risk="72"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="71"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="63"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Sinus tachycardia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="72"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="71"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="63"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="71"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="63"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="71"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="63"/>
              </event>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="71"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="63"/>
              </event>
              <event>
                <sub_title>Oral pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="71"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="63"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="72"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="71"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="63"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="71"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="63"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="72"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="71"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="63"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Stoma site infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="71"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="63"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="71"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="63"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="72"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="71"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="63"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Thromboembolic event</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="71"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="63"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>CTCAEV4.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="72"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="71"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="63"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="72"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="71"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="63"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="72"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="71"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="63"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="71"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="63"/>
              </event>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="71"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="63"/>
              </event>
              <event>
                <sub_title>Esophageal pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="71"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="63"/>
              </event>
              <event>
                <sub_title>Gastrointestinal disorders - Other, specify</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="72"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="71"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="63"/>
              </event>
              <event>
                <sub_title>Mucositis oral</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="72"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="71"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="63"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="72"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="71"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="63"/>
              </event>
              <event>
                <sub_title>Oral dysesthesia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="72"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="71"/>
                <counts group_id="E3" events="3" subjects_affected="2" subjects_at_risk="63"/>
              </event>
              <event>
                <sub_title>Oral pain</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="72"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="71"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="63"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="71"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="63"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="7" subjects_affected="6" subjects_at_risk="72"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="71"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="63"/>
              </event>
              <event>
                <sub_title>General disorders and administration site conditions - Other, specify</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="72"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="71"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="63"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="72"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="71"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="63"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bronchial infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="71"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="63"/>
              </event>
              <event>
                <sub_title>Mucosal infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="71"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="63"/>
              </event>
              <event>
                <sub_title>Pharyngitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="71"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="63"/>
              </event>
              <event>
                <sub_title>Stoma site infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="71"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="63"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Weight loss</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="71"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="63"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="71"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="63"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="72"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="71"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="63"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Akathisia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="71"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="63"/>
              </event>
              <event>
                <sub_title>Dysesthesia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="72"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="71"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="63"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="72"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="71"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="63"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="72"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="71"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="63"/>
              </event>
              <event>
                <sub_title>Paresthesia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="72"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="71"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="63"/>
              </event>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="72"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="71"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="63"/>
              </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="72"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="71"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="63"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="72"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="71"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="63"/>
              </event>
              <event>
                <sub_title>Hiccups</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="71"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="63"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Body odor</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="72"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="71"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="63"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="71"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="63"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="71"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="63"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Robert C. Miller, MD, MS</name_or_title>
      <organization>Mayo Clinic</organization>
      <phone>904-953-1003</phone>
      <email>miller.robert@mayo.edu</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02229539
org study id: A221304
secondary id: U10CA037447
secondary id: UG1CA189823
secondary id: NCI-2014-01877
nct id: NCT02229539
lead sponsor: 
collaborator: 
has dmc: Yes
The purpose of this study is to test whether a mouthwash made with a drug called doxepin can
      reduce the pain caused by mouth sores resulting from radiation therapy. A number of mouth
      rinse preparations exist for patients with treatment-related oral mucositis pain such as the
      DLA rinse, an over-the-counter medication. This study will evaluate the effects of doxepin
      compared to DLA (diphenhydramine, lidocaine and antacids) and placebo.Doxepin is approved by
      the Food and Drug Administration (FDA) for the treatment of depression, anxiety, long-term
      pain management, as well as management of rash.
Patients are stratified according to sex (male vs. female), concurrent use of chemotherapy
      (no vs. yes), patient age at registration (< 60 years old vs. ≥ 60 years old and RTOG acute
      radiation morbidity criteria (1 vs. 2 vs 3 or more). Protocol therapy will consist of 2
      cycles. Patients are randomized to one of three treatment regimens, which include doxepin,
      DLA and placebo. Cycle One will consist of one day. The care provider or nurse will confirm
      that the oral pain is at least 4 out of 10 severity level at the time of the rinse on the
      first day of the study. Patient will be asked to complete the baseline evaluation in the Oral
      Symptoms booklet. If the pain score is less than 4 then administration will be delayed until
      the pain is at least 4. Cycle Two will consist of an optional continuation phase lasting up
      to 7 days. Initiation of the Cycle 2/Continuation Phase may be delayed up to one week after
      Cycle 1/Day 1.

      Primary Objective:

      1. Determine whether the doxepin rinse or DLA rinse is more effective than placebo in
      reducing OM-related pain in patients undergoing RT to the oral cavity, as measured by a
      patient-reported questionnaire at baseline, 5 minutes, 15 minutes, 30 minutes, 1 hour, 2
      hours, and 4 hours.

      Secondary Objectives:

        1. Assess the adverse event profile of the doxepin rinse, the DLA rinse agent, and the
           placebo using a patient-reported questionnaire at 5 minutes, 15 minutes, 30 minutes, 1
           hour, 2 hours, and 4 hours for domains of unpleasant taste, burning or stinging
           discomfort, and drowsiness.

        2. Compare the incidence of using additional analgesics between 1 and 4 hours after the
           initial mouthwash, between the doxepin oral rinse, the DLA rinse agent, and the placebo
           arms.

        3. Compare the length of time that each study product is used by patients in the one-week
           continuation phase.

        4. Compare the daily pain scores in the one-week continuation phase for the three study
           arms.

        5. Compare the 24-hour morphine equivalent dose used in the continuation phase for the
           three study arms.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Mean Area Under the Curve (AUC) of Total Pain Reduction
time frame: Baseline, 5, 15, 30, 60, 120, 240 minutes post treatment
description: Total pain reduction (mouth and throat) was measured by the numerical analogue scale of mouth pain on a scale of 0 to 10, with 0=no pain and 10=worst pain in the questionnaires taken at baseline, and 5, 15, 30, 60, 120, 240 minutes after assigned treatment for doxepin or DLA vs. placebo. The total pain reduction was calculated by the (average of mouth and throat) area under the curve (AUC) adjusting for baseline, with time scale (baseline, 5, 15, 30, 60, 120 and 240 minutes post treatment) replaced by a numerical scale of 0, 1, 2, 3, 4, 5 and 6 respectively. The AUC was prorated when there are terminal missing data. If the missing data were intermittent, simple imputation by trapezoidal rules were applied to calculate the AUC. If a patient cancelled, was missing baseline data, or only provided baseline data, he/she was excluded from the statistical analysis.
measure: The Total Unpleasant Taste of the Oral Rinse as Measured by the Numerical Analogue Scale of Taste of the Oral Rinse in the Questionnaires
time frame: Up to 4 hours post-treatment
measure: The Total Stinging or Burning From the Oral Rinse as Measured by the Numerical Analogue Scale of Stinging or Burning From the Oral Rinse in the Questionnaires
time frame: Up to 4 hours post-treatment
measure: The Total Drowsiness Increase as Measured by the Numerical Analogue Scale of Drowsiness Questionnaires
time frame: Up to 4 hours post-treatment every 4 hours while on treatment
measure: The Incidence of Using Alternative Analgesics Between 1 and 4 Hours After Initial Mouthwash
time frame: Up to 4 hours post-treatment
measure: Patient Preference for Continued Therapy With Oral Rinse After Initial Test Rinse Phase, as Measured by Item 9 in the Patient-reported Questionnaire After 4 Hours
time frame: Up to 4 hours post-treatment
measure: The Length of Time in the Continuation Phase
time frame: Up to 4 hours post-treatment
measure: Pain Score in the Continuation Phase
time frame: Up to 4 hours post-treatment
measure: Alternative Analgesics Use in the Continuation Phase
time frame: Up to 4 hours post-treatment
arm group label: doxepin rinse
arm group type: Experimental
description: Patients receive 2.5 mL (25 mg) doxepin and 2.5 mL water orally. Doxepin rinse is administered in the clinic on Day 1 (Cycle 1). There is an optional continuation phase within seven days following Day 1 (Cycle 1), patients will be encouraged to continue treatment with the study agent for an additional week (Cycle 2) where the patient takes the rinse at home every 4 hours. Chemotherapy is allowed during the continuation phase. Patients randomized to doxepin or placebo, they and their caregivers will continue to be blinded to the treatment.
Patients will complete the Oral Symptoms booklet per the protocol.
arm group label: DLA (diphenhydramine, lidocaine and antacid) rinse
arm group type: Active Comparator
description: Patients receive 5.0 mL DLA orally. DLA is administered in the clinic on Day 1 (Cycle 1). There is an optional continuation phase within seven days following Day 1 (Cycle 1), patients will be encouraged to continue treatment with the study agent for an additional week (Cycle 2) where the patient takes the rinse at home every 4 hours. Chemotherapy is allowed during the continuation phase. Patients receiving DLA during the continuation phase of the study, they and/or caregivers may be aware that they are receiving DLA.
Patients will complete the Oral Symptoms booklet per the protocol.
arm group label: placebo rinse
arm group type: Placebo Comparator
description: Patients receive 2.5 mL placebo and 2.5 mL water orally. The placebo rinse is administered in the clinic on Day 1 (Cycle 1). There is an optional continuation phase within seven days following Day 1 (Cycle 1), patients will be encouraged to continue treatment with the study agent for an additional week (Cycle 2) where the patient takes the rinse at home every 4 hours. Chemotherapy is allowed during the continuation phase. Patients randomized to doxepin or placebo, they and their caregivers will continue to be blinded to the treatment.
Patients will complete the Oral Symptoms booklet per the protocol.
intervention type: Drug
intervention name: doxepin hydrochloride oral solution
description: 2.5 mL (25 mg) doxepin and 2.5 mL water administered orally
arm group label: doxepin rinse
intervention type: Drug
intervention name: DLA (diphenhydramine, lidocaine and antacids) rinse
description: 5.0 mL administered orally
arm group label: DLA (diphenhydramine, lidocaine and antacid) rinse
intervention type: Other
intervention name: Placebo
description: 2.5 mL placebo and 2.5 mL water administered orally
arm group label: placebo rinse
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Robert Miller, MD, MS
role: Study Chair
affiliation: Mayo Clinic
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Mucositis
mesh term: Stomatitis
mesh term: Diphenhydramine
mesh term: Promethazine
mesh term: Lidocaine
mesh term: Doxepin
mesh term: Antacids
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 