Doxepin and a Topical Rinse in the Treatment of Acute Oral Mucositis Pain in Patients Receiving Radiotherapy With or Without Chemotherapy
Condition: Acute Oral Mucositis Pain
MeSH terms: Mucositis; Stomatitis
Intervention: doxepin hydrochloride oral solution; DLA (diphenhydramine, lidocaine and antacids) rinse; Placebo
Intervention description: 2.5 mL (25 mg) doxepin and 2.5 mL water administered orally; 5.0 mL administered orally; 2.5 mL placebo and 2.5 mL water administered orally
Intervention MeSH terms: Diphenhydramine; Promethazine; Lidocaine; Doxepin; Antacids
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 275.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        1. Documentation of Disease: Histologic documentation of malignancy currently undergoing
             a course of RT (with or without chemotherapy) including the oral cavity and/or
             oropharyngeal area to a dose of at least 4500 cGy using more than 5 fractions (i.e.,
             stereotactic body radiation therapy [SBRT] is not allowed).

          2. Physical exam demonstrating evidence of radiotherapy-related mucositis in the visible
             oral cavity and/or oropharynx consistent with mucous membrane toxicity greater than 0
             using the Acute Radiation Morbidity Scoring Criteria.

          3. At least 4 (out of 10) patient-reported oral pain related to oral mucositis secondary
             to RT for which the patient seeks relief, as measured on the Oral Pain Assessment.

             Note: The pain score must be at least 4 at the time that the patient starts the first
             dose of study medication. The patient may be enrolled to the study if s/he, at times,
             has a pain score of at least 4, so long as initiation of study treatment begins when
             the pain score is at least 4.

          4. Ability to complete questionnaire(s) by themselves or with assistance.

          5. No known allergy to diphenhydramine, lidocaine, antacid (aluminum hydroxide, magnesium
             hydroxide, and simethicone), doxepin, tricyclic antidepressants, or any known
             component of the drug formulation in the testing arms.

          6. No use of any anti-arrhythmic medication (except for beta-blockers) including
             lidocaine, linezolid, ipratropium, or medications with high anti-cholinergic potency
             (including neostigmine, a tricyclic antidepressant or a monoamine oxidase inhibitor)
             within 2 weeks prior to registration.

          7. No current diagnosed untreated or unresolved oral candidiasis or oral HSV infection.

          8. No history of untreated narrow angle glaucoma within 6 weeks prior to registration.

          9. No untreated urinary retention within 6 weeks prior to registration.

         10. No current use of glutamine or sucralfate powders at the time of registration (no
             washout required).

         11. No cryotherapy for prophylactic mucosal protection within 6 weeks prior to
             registration.

         12. Not pregnant, because patients eligible for this study will be receiving radiotherapy,
             which has known genotoxic, mutagenic and teratogenic effects. Therefore, for women of
             childbearing potential only, a negative pregnancy test done ≤ 28 days prior to
             registration is required.

         13. Age ≥ 18 years

         14. ECOG Performance Status 0, 1, or 2