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

Phase 3

Completed

Conditions: Acute Oral Mucositis Pain

Interventions: Drug: DLA (diphenhydramine, lidocaine and antacids) rinse
Drug: doxepin hydrochloride oral solution
Other: Placebo

Registration Number: NCT02229539

Lead Sponsor: Alliance for Clinical Trials in Oncology

Brief 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.

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 275

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
DLA (diphenhydramine, lidocaine and antacid) rinse	DLA (diphenhydramine, lidocaine and antacids) rinse	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.
doxepin rinse	doxepin hydrochloride oral solution	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.
placebo rinse	Placebo	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.

Primary Outcome Measures

Name	Time	Method
Mean Area Under the Curve (AUC) of Total Pain Reduction	Baseline, 5, 15, 30, 60, 120, 240 minutes post treatment	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.

Secondary Outcome Measures

Name	Time	Method
Area Under the Curve (AUC) of Total Unpleasant Taste of the Oral Rinse	5, 15, 30, 60, 120, 240 minutes post treatment	Total unpleasant taste was measured by the numerical analogue scale of taste of the oral rinse on a scale of 0 to 10, with 0=acceptable and 10=terrible in the questionnaires taken at 5, 15, 30, 60, 120, 240 minutes after assigned treatment for doxepin or DLA vs. placebo. The total unpleasant taste was calculated by the area under the curve (AUC) adjusting for 5 minutes post treatment, with time scale (5, 15, 30, 60, 120 and 240 minutes post treatment) replaced by a numerical scale of 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 5 minutes after treatment data, or only provided 5 minutes after treatment data, he/she was excluded from the statistical analysis.
Area Under the Curve (AUC) of Total Stinging or Burning From the Oral Rinse	5, 15, 30, 60, 120, 240 minutes post treatment	Total stinging or burning was measured by the numerical analogue scale of stinging or burning from the oral rinse on a scale of 0 to 10, with 0=no stinging or burning and 10=worst stinging or burning possible in the questionnaires taken at 5, 15, 30, 60, 120, 240 minutes after assigned treatment for doxepin or DLA vs. placebo. The total stinging or burning was calculated by the area under the curve (AUC) adjusting for 5 minutes post treatment, with time scale (5, 15, 30, 60, 120 and 240 minutes post treatment) replaced by a numerical scale of 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 5 minutes after treatment data, or only provided 5 minutes after treatment data, he/she was excluded from the statistical analysis.
Area Under the Curve (AUC) of Total Drowsiness	Baseline, 5, 15, 30, 60, 120, 240 minutes post treatment	Total drowsiness was measured by the numerical analogue scale of drowsiness on a scale of 0 to 10, with 0=no drowsiness and 10=extreme drowsiness, leading to sleep 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 drowsiness was calculated by the 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.
The Incidence of Using Alternative Analgesics	At 120 and 240 minutes post treatment	Patients were asked if they have taken any other pain medications, if yes, to record the name, strength and when they have taken the pain medications in the 120 minutes and 240 minutes post treatment questionnaires.
Patient Preference for Continued Therapy With Oral Rinse After Initial Test Rinse Phase	At 240 minutes post treatment	Patients were asked: "Based on your experience with this current oral rinsing medication, would you want to take another dose now if it were available?" in the 240 minutes post treatment questionnaire.
Frequency of Study Rinse Used in the Continuation Phase	Up to 7 days.	Patients were asked: "Did you use the study rinse today?" daily questionnaire during the optional continuation phase (Cycle 2).
Median Mouth Pain Score in the Continuation Phase	Day 1 to Day 7 in the Continuation Phase	Mouth pain scores was measured using the numerical analogue scale ranging from scale of 0 to 10, with 0=no pain and 10=worst pain daily during the optional continuation phase (Cycle 2).
The Incidence of Using Alternative Analgesics in the Continuation Phase	Day 1 to Day 7 in the Continuation Phase	Patients were asked if they have taken any medications for pain over the past 24 hours, if yes, to record the name, strength and when they have taken the pain medications daily during the optional continuation phase (Cycle 2).

Trial Locations

Locations (348): Anchorage Radiation Therapy Center
🇺🇸
Anchorage, Alaska, United States
Alaska Breast Care and Surgery LLC
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Anchorage, Alaska, United States
Alaska Oncology and Hematology LLC
🇺🇸
Anchorage, Alaska, United States
Alaska Regional Hospital
🇺🇸
Anchorage, Alaska, United States
Alaska Women's Cancer Care
🇺🇸
Anchorage, Alaska, United States
Anchorage Oncology Centre
🇺🇸
Anchorage, Alaska, United States
Katmai Oncology Group
🇺🇸
Anchorage, Alaska, United States
Providence Alaska Medical Center
🇺🇸
Anchorage, Alaska, United States
Providence Saint Joseph Medical Center/Disney Family Cancer Center
🇺🇸
Burbank, California, United States
Epic Care-Dublin
🇺🇸
Dublin, California, United States
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Anchorage Radiation Therapy Center
🇺🇸Anchorage, Alaska, United States