Head and Neck CancerPhase 3NCT01156142
Doxepin Hydrochloride in Treating Oral Mucositis Pain in Patients With Head and Neck Cancer Undergoing Radiation Therapy With or Without Chemotherapy
A Phase 3 study testing doxepin hydrochloride in people with Head and Neck Cancer and Mucositis, run by Alliance for Clinical Trials in Oncology at 120 sites in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Head and Neck Cancer, Mucositis, Oral Complications of Radiation Therapy
- What is being tested?
- doxepin hydrochloride
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 155 participants
- Where
- 120 sitesUnited States
- Study dates
- Dec 2010to 2 Mar 2015
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ≥ 18 years of age
- 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.
- ≥ 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.
- Ability to complete questionnaire(s) independently or with assistance
- ECOG Performance Status 0, 1 or 2.
- Provide informed written consent.
- Willingness to return to enrolling institution for follow-up.
Who cannot join
- Known allergy to doxepin, tricyclic antidepressants, or any known component of the drug formulation
- Use of a tricyclic antidepressant or monoamine oxidase inhibitor within the 2 weeks prior to registration
- Current untreated or unresolved oral candidiasis or oral HSV infection
- Current untreated narrow angle glaucoma
- Current untreated urinary retention ≤ 6 weeks prior to registration
- 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
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- 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
Trial locations and contacts
120 sites in 1 country.
120 sites in 1 country
United States120 sites
Hickman Cancer Center at Bixby Medical Center
Adrian, Michigan, 49221
McFarland Clinic, PC
Ames, Iowa, 50010
Saint Joseph Mercy Cancer Center
Ann Arbor, Michigan, 48106-0995
CCOP - Michigan Cancer Research Consortium
Ann Arbor, Michigan, 48106
MBCCOP - Medical College of Georgia Cancer Center
Augusta, Georgia, 30912
Battle Creek Health System Cancer Care Center
Battle Creek, Michigan, 49017
MeritCare Bemidji
Bemidji, Minnesota, 56601
Sanford Clinic North-Bemidgi
Bemidji, Minnesota, 56601
Mecosta County Medical Center
Big Rapids, Michigan, 49307
Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical Center
Boise, Idaho, 83706
Boston University Cancer Research Center
Boston, Massachusetts, 02118
Wood County Oncology Center
Bowling Green, Ohio, 43402
Fairview Ridges Hospital
Burnsville, Minnesota, 55337
Cedar Rapids Oncology Associates
Cedar Rapids, Iowa, 52403
Mercy Regional Cancer Center at Mercy Medical Center
Cedar Rapids, Iowa, 52403
Marshfield Clinic - Chippewa Center
Chippewa Falls, Wisconsin, 54729
Mercy and Unity Cancer Center at Mercy Hospital
Coon Rapids, Minnesota, 55433
Oakwood Cancer Center at Oakwood Hospital and Medical Center
Dearborn, Michigan, 48123-2500
Saint John Hospital and Medical Center
Detroit, Michigan, 48236
Center for Cancer Treatment & Prevention at Sacred Heart Hospital
Eau Claire, Wisconsin, 54701
Marshfield Clinic Cancer Care at Regional Cancer Center
Eau Claire, Wisconsin, 54701
Fairview Southdale Hospital
Edina, Minnesota, 55435
Elkhart Clinic, LLC
Elkhart, Indiana, 46514-2098
Michiana Hematology-Oncology, PC - Elkhart
Elkhart, Indiana, 46514
Elkhart General Hospital
Elkhart, Indiana, 46515
Community Cancer Center
Elyria, Ohio, 44035
Hematology Oncology Center
Elyria, Ohio, 44035
MeritCare Broadway
Fargo, North Dakota, 58102
Sanford Clinic North-Fargo
Fargo, North Dakota, 58102
CCOP - MeritCare Hospital
Fargo, North Dakota, 58122
Roger Maris Cancer Center at MeritCare Hospital
Fargo, North Dakota, 58122
Sanford Medical Center-Fargo
Fargo, North Dakota, 58122
Genesys Hurley Cancer Institute
Flint, Michigan, 48503
Hurley Medical Center
Flint, Michigan, 48503
Fredericksburg Oncology, Incorporated
Fredericksburg, Virginia, 22401
Mercy and Unity Cancer Center at Unity Hospital
Fridley, Minnesota, 55432
Genesys Regional Medical Center
Grand Blanc, Michigan, 48439
Altru Cancer Center at Altru Hospital
Grand Forks, North Dakota, 58201
Butterworth Hospital at Spectrum Health
Grand Rapids, Michigan, 49503
CCOP - Grand Rapids
Grand Rapids, Michigan, 49503
Lacks Cancer Center at Saint Mary's Health Care
Grand Rapids, Michigan, 49503
Van Elslander Cancer Center at St. John Hospital and Medical Center
Grosse Pointe Woods, Michigan, 48236
Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center
Hartford, Connecticut, 06105
Hutchinson Area Health Care
Hutchinson, Minnesota, 55350
Allegiance Health
Jackson, Michigan, 49201
Foote Memorial Hospital
Jackson, Michigan, 49201
Mayo Clinic - Jacksonville
Jacksonville, Florida, 32224
Howard Community Hospital
Kokomo, Indiana, 46904
Center for Cancer Therapy at LaPorte Hospital and Health Services
La Porte, Indiana, 46350
Indiana University Health La Porte Hospital
La Porte, Indiana, 46350
Marshfield Clinic - Ladysmith Center
Ladysmith, Wisconsin, 54848
Sparrow Regional Cancer Center
Lansing, Michigan, 48912-1811
Lima Memorial Hospital
Lima, Ohio, 45804
Cancer Resource Center - Lincoln
Lincoln, Nebraska, 68510
St. Mary Mercy Hospital
Livonia, Michigan, 48154
HealthEast Cancer Care at St. John's Hospital
Maplewood, Minnesota, 55109
Minnesota Oncology - Maplewood
Maplewood, Minnesota, 55109
Marshfield Clinic - Marshfield Center
Marshfield, Wisconsin, 54449
Saint Joseph's Hospital
Marshfield, Wisconsin, 54449
Northwest Ohio Oncology Center
Maumee, Ohio, 43537-1839
Virginia Piper Cancer Institute at Abbott - Northwestern Hospital
Minneapolis, Minnesota, 55407
Hennepin County Medical Center - Minneapolis
Minneapolis, Minnesota, 55415
Marshfield Clinic - Lakeland Center
Minocqua, Wisconsin, 54548
Michiana Hematology-Oncology, PC - South Bend
Mishawaka, Indiana, 46545-1470
Saint Joseph Regional Medical Center
Mishawaka, Indiana, 46545-1470
Michiana Hematology Oncology PC-Mishawaka
Mishawaka, Indiana, 46545
Community Cancer Center of Monroe
Monroe, Michigan, 48162
Mercy Memorial Hospital - Monroe
Monroe, Michigan, 48162
Mercy General Health Partners
Muskegon, Michigan, 49444
New Ulm Medical Center
New Ulm, Minnesota, 56073
CCOP - Missouri Valley Cancer Consortium
Omaha, Nebraska, 68106
Immanuel Medical Center
Omaha, Nebraska, 68122
Alegant Health Cancer Center at Bergan Mercy Medical Center
Omaha, Nebraska, 68124
Lakeside Hospital
Omaha, Nebraska, 68130
Creighton University Medical Center
Omaha, Nebraska, 68131-2197
St. Charles Mercy Hospital
Oregon, Ohio, 43616
Toledo Clinic - Oregon
Oregon, Ohio, 43616
Michiana Hematology Oncology PC - Plymouth
Plymouth, Indiana, 46563
St. Joseph Mercy Oakland
Pontiac, Michigan, 48341-2985
Mercy Regional Cancer Center at Mercy Hospital
Port Huron, Michigan, 48060
Ministry Medical Group at Saint Mary's Hospital
Rhinelander, Wisconsin, 54501
Marshfield Clinic - Indianhead Center
Rice Lake, Wisconsin, 54868
Humphrey Cancer Center at North Memorial Outpatient Center
Robbinsdale, Minnesota, 55422-2900
Mayo Clinic Cancer Center
Rochester, Minnesota, 55905
Seton Cancer Institute at Saint Mary's - Saginaw
Saginaw, Michigan, 48601
Lakeland Regional Cancer Care Center - St. Joseph
Saint Joseph, Michigan, 49085
Lakeside Cancer Specialists, PLLC
Saint Joseph, Michigan, 49085
Marie Yeager Cancer Center
Saint Joseph, Michigan, 49085
CCOP - Metro-Minnesota
Saint Louis Park, Minnesota, 55416
Park Nicollet Cancer Center
Saint Louis Park, Minnesota, 55416
Regions Hospital Cancer Care Center
Saint Paul, Minnesota, 55101
United Hospital
Saint Paul, Minnesota, 55102
Mayo Clinic Scottsdale
Scottsdale, Arizona, 85259-5499
St. Francis Cancer Center at St. Francis Medical Center
Shakopee, Minnesota, 55379
CCOP - Northern Indiana CR Consortium
South Bend, Indiana, 46601
Memorial Hospital of South Bend
South Bend, Indiana, 46601
Marshfield Clinic at Saint Michael's Hospital
Stevens Point, Wisconsin, 54481
Saint Michael's Hospital Cancer Center
Stevens Point, Wisconsin, 54481
Lakeview Hospital
Stillwater, Minnesota, 55082
Flower Hospital Cancer Center
Sylvania, Ohio, 43560
Mercy Hospital of Tiffin
Tiffin, Ohio, 44883
Toledo Hospital
Toledo, Ohio, 43606
St. Vincent Mercy Medical Center
Toledo, Ohio, 43608
Medical University of Ohio Cancer Center
Toledo, Ohio, 43614
CCOP - Toledo Community Hospital
Toledo, Ohio, 43617
St. Anne Mercy Hospital
Toledo, Ohio, 43623
Toledo Clinic, Incorporated - Main Clinic
Toledo, Ohio, 43623
Munson Medical Center
Traverse City, Michigan, 49684
CCOP - Carle Cancer Center
Urbana, Illinois, 61801
Ridgeview Medical Center
Waconia, Minnesota, 55387
St. John Macomb Hospital
Warren, Michigan, 48093
Marshfield Clinic - Wausau Center
Wausau, Wisconsin, 54401
Fulton County Health Center
Wauseon, Ohio, 43567
Diagnostic and Treatment Center
Weston, Wisconsin, 54476
Marshfield Clinic - Weston Center
Weston, Wisconsin, 54476
Ministry Saint Clare's Hospital
Weston, Wisconsin, 54476
Michiana Hematology Oncology PC - La Porte
Westville, Indiana, 46391
Willmar Cancer Center at Rice Memorial Hospital
Willmar, Minnesota, 56201
Marshfield Clinic - Wisconsin Rapids Center
Wisconsin Rapids, Wisconsin, 54494
Minnesota Oncology - Woodbury
Woodbury, Minnesota, 55125
About this study
Official title: A Randomized Double-Blind Study of Doxepin Rinse Versus Placebo in the Treatment of Acute Oral Mucositis Pain in Patients Receiving Radiotherapy With or Without Chemotherapy
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.
Read the detailed description
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:
- 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.
- Compare the incidence of using alternative analgesics before 4 hours, between the doxepin oral rinse and placebo arms.
- 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.
- Being tested
- doxepin hydrochloride, placebo
- Keywords
- oral complications of radiation therapy, mucositis, pain, stage I squamous cell carcinoma of the paranasal sinus and nasal cavity, recurrent squamous cell carcinoma of the hypopharynx, squamous cell carcinoma of the hypopharynx, recurrent squamous cell carcinoma of the larynx, recurrent verrucous carcinoma of the larynx, squamous cell carcinoma of the larynx, verrucous carcinoma of the larynx, recurrent adenoid cystic carcinoma of the oral cavity, recurrent mucoepidermoid carcinoma of the oral cavity, recurrent verrucous carcinoma of the oral cavity, adenoid cystic carcinoma of the oral cavity, mucoepidermoid carcinoma of the oral cavity, verrucous carcinoma of the oral cavity, squamous cell carcinoma of the lip and oral cavity, recurrent basal cell carcinoma of the lip, recurrent squamous cell carcinoma of the lip and oral cavity, basal cell carcinoma of the lip
- Medical subject headings
- Head and Neck Neoplasms, Mucositis, Pain, Squamous Cell Carcinoma of Head and Neck, Esthesioneuroblastoma, Olfactory, Salivary Gland Neoplasms, Tongue Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
doxepin hydrochlorideDrug
Oral rinse
placeboOther
Oral rinse
| Study group | Role | What they receive |
|---|---|---|
| Arm I | Experimental | 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. Receives: Drug: doxepin hydrochloride |
| Arm II | Placebo comparator | Patients receive placebo oral rinse (swish, gargle, and spit) over 1 minute on day 1. Patients may crossover to arm I on day 2. Receives: Other: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline and Day 1
Secondary outcomes (5)
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.
Measured: 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.
Measured: 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.
Measured: 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 .
Measured: 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.
Measured: Up to 9 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jul 2010 (estimated)
- Study startDec 2010
- Primary completionMay 2012
- Study completion2 Mar 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Head and Neck CancerStudies of the same condition, open and under way.
- More trials run by Alliance for Clinical Trials in OncologyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 155 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alliance for Clinical Trials in Oncology
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Robert C. Miller, MD, Study chair, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01156142
- Sponsor's protocol ID
- NCCTG-N09C6
- Other IDs
- NCI-2011-02049, CDR0000675520, U10CA037404
- Status last verified
- Jul 2017
- First submitted
- 1 Jul 2010
- Last updated
- 9 Aug 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Leenstra JL, Miller RC, Qin R, Martenson JA, Dornfeld KJ, Bearden JD, Puri DR, Stella PJ, Mazurczak MA, Klish MD, Novotny PJ, Foote RL, Loprinzi CL. Doxepin rinse versus placebo in the treatment of acute oral mucositis pain in patients receiving head and neck radiotherapy with or without chemotherapy: a phase III, randomized, double-blind trial (NCCTG-N09C6 [Alliance]). J Clin Oncol. 2014 May 20;32(15):1571-7. doi: 10.1200/JCO.2013.53.2630. Epub 2014 Apr 14.
PubMed 24733799
Study at a glance
From the registry record, last updated by the sponsor on 9 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Double-Blind Study of Doxepin Rinse Versus Placebo in the Treatment of Acute Oral Mucositis Pain in Patients Receiving Radiotherapy With or Without Chemotherapy
- ClinicalTrials.gov ID
- NCT01156142
- Acronym / sponsor ID
- NCCTG-N09C6
- Keywords
- oral complications of radiation therapy, mucositis, pain, stage I squamous cell carcinoma of the paranasal sinus and nasal cavity, recurrent squamous cell carcinoma of the hypopharynx, squamous cell carcinoma of the hypopharynx, recurrent squamous cell carcinoma of the larynx, recurrent verrucous carcinoma of the larynx
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 155 participants (actual)
- Lead sponsor
- Alliance for Clinical Trials in OncologyUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Dec 2010
- Primary completion
- May 2012 (actual)
- Study completion
- 2 Mar 2015 (actual)
- First posted
- 2 Jul 2010 (estimated)
- Results
- Posted 8 May 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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:
- 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.
- Compare the incidence of using alternative analgesics before 4 hours, between the doxepin oral rinse and placebo arms.
- 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.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I | Experimental | Drug: doxepin hydrochloridePatients 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 | Placebo comparator | Other: placeboPatients receive placebo oral rinse (swish, gargle, and spit) over 1 minute on day 1. Patients may crossover to arm I on day 2. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- ≥ 18 years of age
- 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.
- ≥ 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.
- Ability to complete questionnaire(s) independently or with assistance
- ECOG Performance Status 0, 1 or 2.
Key exclusion criteria (10 listed)
- Known allergy to doxepin, tricyclic antidepressants, or any known component of the drug formulation
- Use of a tricyclic antidepressant or monoamine oxidase inhibitor within the 2 weeks prior to registration
- Current untreated or unresolved oral candidiasis or oral HSV infection
- Current untreated narrow angle glaucoma
- Current untreated urinary retention ≤ 6 weeks prior to registration
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| doxepin hydrochlorideOral rinse | Drug | Arm I |
| placeboOral rinse | Other | Arm II |
Primary outcome
Total Pain Reduction (Mouth and Throat)
Time frame: Baseline and Day 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.
5 secondary outcomes
Total Taste of the Oral Rinse
Time frame: Up to 9 days
Total Stinging or Burning From the Oral Rinse
Time frame: Up to 9 days
Total Drowsiness Increase
Time frame: Up to 9 days
Incidence of Using Alternative Analgesics Between 2 and 4 Hours After the Initial Mouthwash
Time frame: Up to 9 days
Patient Preference for Continuing Therapy With Oral Doxepin Hydrochloride
Time frame: Up to 9 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Aug 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 24733799Leenstra JL, Miller RC, Qin R, Martenson JA, Dornfeld KJ, Bearden JD, Puri DR, Stella PJ, Mazurczak MA, Klish MD, Novotny PJ, Foote RL, Loprinzi CL. Doxepin rinse versus placebo in the treatment of acute oral mucositis pain in patients receiving head and neck radiotherapy with or without chemotherapy: a phase III, randomized, double-blind trial (NCCTG-N09C6 [Alliance]). J Clin Oncol. 2014 May 20;32(15):1571-7. doi: 10.1200/JCO.2013.53.2630. Epub 2014 Apr 14.
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RecruitingPhase 2
Proton Spatially Fractionated Radiotherapy or Photon Stereotactic Body Radiotherapy in Combination With Pembrolizumab Before Surgery for the Treatment of Locally Advanced and Radiation-Naive Locoregionally Recurrent Oral Cavity Cancer, OSPRI Trial
Locally Advanced Oral Cavity Squamous Cell Carcinoma, Locally Recurrent Oral Cavity Squamous Cell Carcinoma
RecruitingPhase 4
Lidocaine Infiltration and Neuroimmunomodulation in Head and Neck Cancer Surgery
Head and Neck Cancer (H&N)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Robert C. Miller, MD study chair
Mayo Clinic
120 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing doxepin hydrochloride in people with Head and Neck Cancer and Mucositis, run by Alliance for Clinical Trials in Oncology at 120 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 120 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 May 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Total Pain Reduction (Mouth and Throat) (time frame: Baseline and Day 1). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01156142, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Aug 2017.