NCT02229539|CompletedPhase 3ResultsDMC

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

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

Alliance for Clinical Trials in Oncology ClinicalTrials.gov

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4 other identifiers

A221304U10CA037447UG1CA189823NCI-2014-01877

Study Type

interventional

Target

275

Locations

1 country

Sites

350

Timeline

RegisteredSep 2014

StartedNov 2014

CompletionMar 2019

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.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

275

participants targeted

Target at P50-P75 for phase_3

Timeline

Completed

Started Nov 2014

Typical duration for phase_3

Geographic Reach

1 country

350 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

4.3 years study duration

First Submitted

Initial submission to the registry

August 29, 2014

Completed

3 days until next milestone

First Posted

Study publicly available on registry

September 1, 2014

Completed

3 months until next milestone

Study Start

First participant enrolled

November 18, 2014

Completed

1.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 23, 2016

Completed

11 months until next milestone

Results Posted

Study results publicly available

April 10, 2017

Completed

1.9 years until next milestone

Study Completion

Last participant's last visit for all outcomes

March 15, 2019

Completed

Last Updated

May 18, 2025

Status Verified

May 1, 2025

Enrollment Period

1.5 years

First QC Date

August 29, 2014

Results QC Date

December 7, 2016

Last Update Submit

May 5, 2025

Conditions

Acute Oral Mucositis Pain

Outcome Measures

Primary Outcomes (1)

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

Secondary Outcomes (8)

Area Under the Curve (AUC) of Total Unpleasant Taste of the Oral Rinse
5, 15, 30, 60, 120, 240 minutes post treatment
Area Under the Curve (AUC) of Total Stinging or Burning From the Oral Rinse
5, 15, 30, 60, 120, 240 minutes post treatment
Area Under the Curve (AUC) of Total Drowsiness
Baseline, 5, 15, 30, 60, 120, 240 minutes post treatment
The Incidence of Using Alternative Analgesics
At 120 and 240 minutes post treatment
Patient Preference for Continued Therapy With Oral Rinse After Initial Test Rinse Phase
At 240 minutes post treatment
+3 more secondary outcomes

Study Arms (3)

doxepin rinse

EXPERIMENTAL

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.

Drug: doxepin hydrochloride oral solution

DLA (diphenhydramine, lidocaine and antacid) rinse

ACTIVE COMPARATOR

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.

Drug: DLA (diphenhydramine, lidocaine and antacids) rinse

placebo rinse

PLACEBO COMPARATOR

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.

Other: Placebo

Interventions

doxepin hydrochloride oral solutionDRUG

2.5 mL (25 mg) doxepin and 2.5 mL water administered orally

doxepin rinse

DLA (diphenhydramine, lidocaine and antacids) rinseDRUG

5.0 mL administered orally

DLA (diphenhydramine, lidocaine and antacid) rinse

PlaceboOTHER

2.5 mL placebo and 2.5 mL water administered orally

placebo rinse

Eligibility Criteria

Age18 Years+

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

Alliance for Clinical Trials in Oncologylead
National Cancer Institute (NCI)collaborator

Study Sites (350)

Anchorage Radiation Therapy Center

Anchorage, Alaska, 99504, United States

Location

Alaska Breast Care and Surgery LLC