Doxepin and a Topical Rinse in the Treatment of Acute Oral Mucositis Pain in Patients Receiving Radiotherapy With or Without Chemotherapy
Doxepin and a Topical Rinse in the Treatment of Acute Oral Mucositis Pain in Patients Receiving Radiotherapy With or Without Chemotherapy
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.
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