Doxepin Hydrochloride in Treating Oral Mucositis Pain in Patients With Head and Neck Cancer Undergoing Radiation Therapy With or Without Chemotherapy

OUTLINE: This is a multicenter study. Patients are stratified according to gender,
concurrent radiosensitizing chemotherapy (yes vs no), and age (< 60 years vs ≥ 60 years).
Patients are randomized to 1 of 2 treatment arms.

- Arm I: Patients receive doxepin hydrochloride oral rinse (swish, gargle, and spit)*
over 1 minute on day 1. Patients may crossover to arm II on day 2.

- Arm II: Patients receive placebo oral rinse (swish, gargle, and spit)* over 1 minute on
day 1.

Patients may crossover to arm I on day 2. The primary and secondary objectives are detailed
below.

Primary Objective:

Determine whether doxepin oral rinse is effective in reducing OM-related pain in patients
undergoing RT to the oral cavity, as measured by a patient-reported questionnaire at 5,15,
30, 60, 120 and 240 minutes

Secondary Objectives:

1. Assess the adverse event profile of doxepin rinse using a patient-reported
questionnaire at 5, 15, 30, 60, 120 and 240 minutes for domains of unpleasant taste,
burning or stinging discomfort, and drowsiness.

2. Compare the incidence of using alternative analgesics before 4 hours, between the
doxepin oral rinse and placebo arms.

3. Assess patient preference for continued therapy with oral rinse after initial test
rinse or after the cross-over phase.

NOTE: * Patients are instructed to avoid taking medications for mucositis pain 60 minutes
before and after study medication.

After completing study therapy, patients have the option to receive doxepin hydrochloride
oral rinse every 4 hours as needed during radiotherapy.

Patients complete questionnaires at baseline, and at 5, 15, 30, 60, 120, and 240 minutes
after study medication. Patients who choose to continue doxepin hydrochloride oral rinse
also complete weekly questionnaires.

Inclusion Criteria:

1. ≥ 18 years of age

2. Histologic proof of malignancy currently undergoing a course of RT (with or without
chemotherapy) to a dose of ≥ 5000 cGy using 1.60 to 2.20 Gy per fraction. Note: At
least one third of the oral cavity mucosa must be included in the radiation therapy
fields.

3. ≥ 4 oral pain felt to be related to mucositis for which the patient wants relief as
measured by the Numeric Measure of Oral Pain. Note: An oral exam confirming the
presence of mucositis should be performed by the enrolling clinician in addition to
patient feedback.

4. Ability to complete questionnaire(s) independently or with assistance

5. ECOG Performance Status 0, 1 or 2.

6. Provide informed written consent.

7. Willingness to return to enrolling institution for follow-up.

Exclusion Criteria:

1. Known allergy to doxepin, tricyclic antidepressants, or any known component of the
drug formulation

2. Use of a tricyclic antidepressant or monoamine oxidase inhibitor within the 2 weeks
prior to registration

3. Current untreated or unresolved oral candidiasis or oral HSV infection

4. Current untreated narrow angle glaucoma

5. Current untreated urinary retention ≤ 6 weeks prior to registration

6. Co-morbid systemic illnesses or other severe concurrent disease which, in the
judgment of the investigator, would make the patient inappropriate for entry into
this study or interfere significantly with the proper assessment of safety and
toxicity of the prescribed regimens

7. Any of the following because this study involves a study agent whose genotoxic,
mutagenic and teratogenic effects on the developing fetus and newborn are unknown:

- Pregnant women

- Nursing women

- Men or women of childbearing potential who are unwilling to employ adequate
contraception