A Phase 3 interventional study of doxepin hydrochloride and placebo in Head and Neck Cancer, Mucositis and Oral Complications of Radiation Therapy, sponsored by Alliance for Clinical Trials in Oncology. Completed at 120 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2017-08-09.
Sponsored by Alliance for Clinical Trials in Oncology · Phase 3, Interventional, and Supportive care
RATIONALE: Doxepin hydrochloride may be an effective treatment for oral mucositis pain in patients undergoing radiation therapy with or without chemotherapy.
PURPOSE: This randomized phase III trial is studying doxepin hydrochloride to see how well it works compared to placebo 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.
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:
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.
2,344 studies on the registry are indexed under Head and Neck Neoplasms; 551 are open to participants now.
This study's enrollment of 155 is above the median of 47 across 1,751 interventional studies indexed under Head and Neck Neoplasms.
Browse Head and Neck Neoplasms studies →Alliance for Clinical Trials in Oncology is the lead sponsor of 499 studies on the registry; 27 are open to participants now.
Of its 6 completed or terminated interventional studies of FDA-regulated products, 6 (100%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
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:
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.
Drug: doxepin hydrochloride
Patients receive placebo oral rinse (swish, gargle, and spit) over 1 minute on day 1. Patients may crossover to arm I on day 2.
Other: placebo
Oral rinse
Oral rinse
Total Pain Reduction (Mouth and Throat)
The total pain reduction will be calculated by the (average of mouth and throat) area under the curve (AUC) adjusting for baseline, with time scale replaced by a numerical scale of 1,2,3,4,5,6. The numerical scale will be used rather than the raw time scale in order to give proper weights to more immediate patient-reported mouth pain outcomes after treatment. The AUC will be calculated by proration when there are terminal missing data. If the missing data are intermittent, simple imputation will be applied to calculate the AUC. The question ('On a scale from 0 to 10, what number best describes your MOUTH PAIN due to your radiation treatment now?') used 11-point numerical analog scales (0 (no pain) to 10 (worst pain imaginable or possible) scores) to measure pain. The AUCs for the two treatment arms were compared by using the Wilcoxon rank sum test with 95% CIs.
Time frame: Baseline and Day 1
Total Taste of the Oral Rinse
The total taste of the oral rinse will be calculated by the area under the curve (AUC) adjusting for baseline, with time scale replaced by a numerical scale of 1,2,3,4,5,6 , and analyzed in the same way as the primary endpoint. The numerical scale will be used rather than the raw time scale in order to give proper weights to more immediate patient-reported mouth pain outcomes after treatment. The AUC will be calculated by proration when there are terminal missing data. If the missing data are intermittent, simple imputation will be applied to calculate the AUC. The question ('On a scale from 0 to 10, what number best describes the TASTE OF THE ORAL RINSE now?') used 11-point numerical analog scales (0 (acceptable taste) to 10(terrible taste), with higher values representing worse outcome) to evaluate the total taste of the oral rinse. The AUCs for the two treatment arms were compared by using the Wilcoxon rank sum test with 95% CIs.
Time frame: Up to 9 days
Total Stinging or Burning From the Oral Rinse
The total stinging or burning from the oral rinse will be calculated by the area under the curve (AUC) adjusting for baseline, with time scale replaced by a numerical scale of 1,2,3,4,5,6. The numerical scale will be used rather than the raw time scale in order to give proper weights to more immediate patient-reported mouth pain outcomes after treatment. The AUC will be calculated by proration when there are terminal missing data. If the missing data are intermittent, simple imputation will be applied to calculate the AUC. The question ('On a scale from 0 to 10, what number best describes any STINGING OR BURNING FROM THE ORAL RINSE now?') used 11-point numerical analog scales (0 (no stinging or burning) to 10 (worst stinging or burning possible) scores) to total stinging or burning from the oral rinse. The AUCs for the two treatment arms were compared by using the Wilcoxon rank sum test with 95% CIs.The statistical analysis will be the same as the primary analysis.
Time frame: Up to 9 days
Total Drowsiness Increase
The total drowsiness increase will be calculated by the area under the curve (AUC) adjusting for baseline, with time scale replaced by a numerical scale of 1,2,3,4,5,6. The numerical scale will be used rather than the raw time scale in order to give proper weights to more immediate patient-reported mouth pain outcomes after treatment. The AUC will be calculated by proration when there are terminal missing data. If the missing data are intermittent, simple imputation will be applied to calculate the AUC. The question ('On a scale from 0 to 10, what number best describes your DROWSINESS now?') used 11-point numerical analog scales (0 (no drowsiness) to 10 (extreme drowsiness, leading to sleep) scores) to measure total drowsiness increase. The AUCs for the two treatment arms were compared by using the Wilcoxon rank sum test with 95% CIs. The statistical analysis will be the same as the primary analysis.
Time frame: Up to 9 days
Incidence of Using Alternative Analgesics Between 2 and 4 Hours After the Initial Mouthwash
The incidence of utilizing additional analgesics between 2 and 4 hours after the initial mouthwash will be compared between the arms by the Chi-square test .
Time frame: Up to 9 days
Patient Preference for Continuing Therapy With Oral Doxepin Hydrochloride
After each dose was administered, patients were asked if they would like to continue rinses with that particular agent. The percentage of patients who expressed an interest in continuing therapy are reported below.
Time frame: Up to 9 days
| Milestone | Arm I (Doxepin-Placebo) | Arm II (Placebo-Doxepin) |
|---|---|---|
| Started | 77 | 78 |
| Completed | 69 | 71 |
| Not completed | 8 | 7 |
| Withdrew: Withdrawal by subject | 8 | 6 |
| Withdrew: Ineligible | 0 | 1 |
The total pain reduction will be calculated by the (average of mouth and throat) area under the curve (AUC) adjusting for baseline, with time scale replaced by a numerical scale of 1,2,3,4,5,6. The numerical scale will be used rather than the raw time scale in order to give proper weights to more immediate patient-reported mouth pain outcomes after treatment. The AUC will be calculated by proration when there are terminal missing data. If the missing data are intermittent, simple imputation will be applied to calculate the AUC. The question ('On a scale from 0 to 10, what number best describes your MOUTH PAIN due to your radiation treatment now?') used 11-point numerical analog scales (0 (no pain) to 10 (worst pain imaginable or possible) scores) to measure pain. The AUCs for the two treatment arms were compared by using the Wilcoxon rank sum test with 95% CIs.
| units on a scale | Arm I (Doxepin-Placebo) | Arm II (Placebo-Doxepin) |
|---|---|---|
| Total Pain Reduction (Mouth and Throat) | -9.1 ± 7.9 | -4.7 ± 6.1 |
The total taste of the oral rinse will be calculated by the area under the curve (AUC) adjusting for baseline, with time scale replaced by a numerical scale of 1,2,3,4,5,6 , and analyzed in the same way as the primary endpoint. The numerical scale will be used rather than the raw time scale in order to give proper weights to more immediate patient-reported mouth pain outcomes after treatment. The AUC will be calculated by proration when there are terminal missing data. If the missing data are intermittent, simple imputation will be applied to calculate the AUC. The question ('On a scale from 0 to 10, what number best describes the TASTE OF THE ORAL RINSE now?') used 11-point numerical analog scales (0 (acceptable taste) to 10(terrible taste), with higher values representing worse outcome) to evaluate the total taste of the oral rinse. The AUCs for the two treatment arms were compared by using the Wilcoxon rank sum test with 95% CIs.
| units on a scale | Arm I (Doxepin-Placebo) | Arm II (Placebo-Doxepin) |
|---|---|---|
| Total Taste of the Oral Rinse | 7.7 ± 7.1 | 5.1 ± 7.7 |
The total stinging or burning from the oral rinse will be calculated by the area under the curve (AUC) adjusting for baseline, with time scale replaced by a numerical scale of 1,2,3,4,5,6. The numerical scale will be used rather than the raw time scale in order to give proper weights to more immediate patient-reported mouth pain outcomes after treatment. The AUC will be calculated by proration when there are terminal missing data. If the missing data are intermittent, simple imputation will be applied to calculate the AUC. The question ('On a scale from 0 to 10, what number best describes any STINGING OR BURNING FROM THE ORAL RINSE now?') used 11-point numerical analog scales (0 (no stinging or burning) to 10 (worst stinging or burning possible) scores) to total stinging or burning from the oral rinse. The AUCs for the two treatment arms were compared by using the Wilcoxon rank sum test with 95% CIs.The statistical analysis will be the same as the primary analysis.
| units on a scale | Arm I (Doxepin-Placebo) | Arm II (Placebo-Doxepin) |
|---|---|---|
| Total Stinging or Burning From the Oral Rinse | 9.6 ± 8.4 | 4.0 ± 8.0 |
The total drowsiness increase will be calculated by the area under the curve (AUC) adjusting for baseline, with time scale replaced by a numerical scale of 1,2,3,4,5,6. The numerical scale will be used rather than the raw time scale in order to give proper weights to more immediate patient-reported mouth pain outcomes after treatment. The AUC will be calculated by proration when there are terminal missing data. If the missing data are intermittent, simple imputation will be applied to calculate the AUC. The question ('On a scale from 0 to 10, what number best describes your DROWSINESS now?') used 11-point numerical analog scales (0 (no drowsiness) to 10 (extreme drowsiness, leading to sleep) scores) to measure total drowsiness increase. The AUCs for the two treatment arms were compared by using the Wilcoxon rank sum test with 95% CIs. The statistical analysis will be the same as the primary analysis.
| units on a scale | Arm I (Doxepin-Placebo) | Arm II (Placebo-Doxepin) |
|---|---|---|
| Total Drowsiness Increase | -0.7 ± 10.3 | -2.4 ± 6.6 |
The incidence of utilizing additional analgesics between 2 and 4 hours after the initial mouthwash will be compared between the arms by the Chi-square test .
| percentage of patients | Arm I (Doxepin-Placebo) | Arm II (Placebo-Doxepin) |
|---|---|---|
| At 2 hours after the initial mouthwash | 8.8 | 2.9 |
| At 4 hours after the initial mouthwash | 16.9 | 14.5 |
After each dose was administered, patients were asked if they would like to continue rinses with that particular agent. The percentage of patients who expressed an interest in continuing therapy are reported below.
| percentage of patients | Arm I (Doxepin-Placebo) | Arm II (Placebo-Doxepin) |
|---|---|---|
| Patient Preference for Continuing Therapy With Oral Doxepin Hydrochloride | 77.3 | 51.5 |
Collected over Adverse events are assessed during the Active Monitoring Phase at the following time points: at time Dose 1 of study treatment is administered, at time of Dose 2 crossover, during the Optional Continuation Phase, and at the end of the study. All adverse events are collected during the first day; up to 9 days.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Arm I (Doxepin-Placebo) | — | 0/74 (0%) | 10/74 (13.5%) |
| Arm II (Placebo-Doxepin) | — | 0/75 (0%) | 8/75 (10.7%) |
| Event | Arm I (Doxepin-Placebo) | Arm II (Placebo-Doxepin) |
|---|---|---|
| Mucositis oralGastrointestinal disorders | 4/74 | 6/75 |
| Dry mouthGastrointestinal disorders | 3/74 | 0/75 |
| Oral painGastrointestinal disorders | 2/74 | 2/75 |
| SomnolenceNervous system disorders | 1/74 | 2/75 |
| DiarrheaGastrointestinal disorders | 1/74 | 0/75 |
| DysphagiaGastrointestinal disorders | 1/74 | 0/75 |
| NauseaGastrointestinal disorders | 1/74 | 1/75 |
| Salivary duct inflammationGastrointestinal disorders | 1/74 | 0/75 |
| FatigueGeneral disorders | 1/74 | 0/75 |
| AnorexiaMetabolism and nutrition disorders | 1/74 | 0/75 |
| Age, Continuous(years) | Arm I (Doxepin-Placebo) | Arm II (Placebo-Doxepin) | Total |
|---|---|---|---|
| Mean | 62 (39.0 to 93.0) | 60 (37.0 to 86.0) | 61 (37.0 to 93.0) |
| Sex: Female, Male(Participants) | Arm I (Doxepin-Placebo) | Arm II (Placebo-Doxepin) | Total |
|---|---|---|---|
| Female | 13 | 15 | 28 |
| Male | 56 | 56 | 112 |
| Region of Enrollment(participants) | Arm I (Doxepin-Placebo) | Arm II (Placebo-Doxepin) | Total |
|---|---|---|---|
| United States | 69 | 71 | 140 |
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Alliance for Clinical Trials in Oncology