Doxepin Hydrochloride in Treating Oral Mucositis Pain in Patients With Head and Neck Cancer Undergoing Radiation Therapy With or Without Chemotherapy
- Conditions
- MucositisOral Complications of Radiation TherapyPainHead and Neck Cancer
- Interventions
- Other: placebo
- Registration Number
- NCT01156142
- Lead Sponsor
- Alliance for Clinical Trials in Oncology
- Brief 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 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:
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 155
- ≥ 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.
-
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
-
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Arm II placebo Patients receive placebo oral rinse (swish, gargle, and spit) over 1 minute on day 1. Patients may crossover to arm I on day 2. Arm I doxepin hydrochloride 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.
- Primary Outcome Measures
Name Time Method Total Pain Reduction (Mouth and Throat) 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.
- Secondary Outcome Measures
Name Time Method Total Taste of the Oral Rinse Up to 9 days 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.
Total Stinging or Burning From the Oral Rinse Up to 9 days 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.
Total Drowsiness Increase Up to 9 days 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.
Incidence of Using Alternative Analgesics Between 2 and 4 Hours After the Initial Mouthwash Up to 9 days 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 .
Patient Preference for Continuing Therapy With Oral Doxepin Hydrochloride Up to 9 days 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.
Trial Locations
- Locations (120)
Hurley Medical Center
🇺🇸Flint, Michigan, United States
Regions Hospital Cancer Care Center
🇺🇸Saint Paul, Minnesota, United States
Altru Cancer Center at Altru Hospital
🇺🇸Grand Forks, North Dakota, United States
Park Nicollet Cancer Center
🇺🇸Saint Louis Park, Minnesota, United States
United Hospital
🇺🇸Saint Paul, Minnesota, United States
Marshfield Clinic - Wausau Center
🇺🇸Wausau, Wisconsin, United States
Diagnostic and Treatment Center
🇺🇸Weston, Wisconsin, United States
Northwest Ohio Oncology Center
🇺🇸Maumee, Ohio, United States
Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center
🇺🇸Hartford, Connecticut, United States
Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical Center
🇺🇸Boise, Idaho, United States
Battle Creek Health System Cancer Care Center
🇺🇸Battle Creek, Michigan, United States
CCOP - Grand Rapids
🇺🇸Grand Rapids, Michigan, United States
Allegiance Health
🇺🇸Jackson, Michigan, United States
Foote Memorial Hospital
🇺🇸Jackson, Michigan, United States
Seton Cancer Institute at Saint Mary's - Saginaw
🇺🇸Saginaw, Michigan, United States
Community Cancer Center of Monroe
🇺🇸Monroe, Michigan, United States
Mercy General Health Partners
🇺🇸Muskegon, Michigan, United States
Marie Yeager Cancer Center
🇺🇸Saint Joseph, Michigan, United States
Marshfield Clinic - Marshfield Center
🇺🇸Marshfield, Wisconsin, United States
Saint Michael's Hospital Cancer Center
🇺🇸Stevens Point, Wisconsin, United States
Saint Joseph's Hospital
🇺🇸Marshfield, Wisconsin, United States
Marshfield Clinic - Lakeland Center
🇺🇸Minocqua, Wisconsin, United States
Ministry Medical Group at Saint Mary's Hospital
🇺🇸Rhinelander, Wisconsin, United States
Marshfield Clinic - Indianhead Center
🇺🇸Rice Lake, Wisconsin, United States
Michiana Hematology-Oncology, PC - Elkhart
🇺🇸Elkhart, Indiana, United States
Howard Community Hospital
🇺🇸Kokomo, Indiana, United States
Center for Cancer Therapy at LaPorte Hospital and Health Services
🇺🇸La Porte, Indiana, United States
Saint Joseph Regional Medical Center
🇺🇸Mishawaka, Indiana, United States
Michiana Hematology Oncology PC - Plymouth
🇺🇸Plymouth, Indiana, United States
Michiana Hematology Oncology PC - La Porte
🇺🇸Westville, Indiana, United States
Ministry Saint Clare's Hospital
🇺🇸Weston, Wisconsin, United States
Marshfield Clinic - Weston Center
🇺🇸Weston, Wisconsin, United States
McFarland Clinic, PC
🇺🇸Ames, Iowa, United States
Mercy Regional Cancer Center at Mercy Medical Center
🇺🇸Cedar Rapids, Iowa, United States
Genesys Regional Medical Center
🇺🇸Grand Blanc, Michigan, United States
Lacks Cancer Center at Saint Mary's Health Care
🇺🇸Grand Rapids, Michigan, United States
Butterworth Hospital at Spectrum Health
🇺🇸Grand Rapids, Michigan, United States
Sparrow Regional Cancer Center
🇺🇸Lansing, Michigan, United States
Van Elslander Cancer Center at St. John Hospital and Medical Center
🇺🇸Grosse Pointe Woods, Michigan, United States
St. Mary Mercy Hospital
🇺🇸Livonia, Michigan, United States
Mercy Memorial Hospital - Monroe
🇺🇸Monroe, Michigan, United States
St. Joseph Mercy Oakland
🇺🇸Pontiac, Michigan, United States
Lakeland Regional Cancer Care Center - St. Joseph
🇺🇸Saint Joseph, Michigan, United States
Lakeside Cancer Specialists, PLLC
🇺🇸Saint Joseph, Michigan, United States
St. John Macomb Hospital
🇺🇸Warren, Michigan, United States
HealthEast Cancer Care at St. John's Hospital
🇺🇸Maplewood, Minnesota, United States
Hutchinson Area Health Care
🇺🇸Hutchinson, Minnesota, United States
CCOP - Metro-Minnesota
🇺🇸Saint Louis Park, Minnesota, United States
Ridgeview Medical Center
🇺🇸Waconia, Minnesota, United States
Willmar Cancer Center at Rice Memorial Hospital
🇺🇸Willmar, Minnesota, United States
Cancer Resource Center - Lincoln
🇺🇸Lincoln, Nebraska, United States
Lima Memorial Hospital
🇺🇸Lima, Ohio, United States
Wood County Oncology Center
🇺🇸Bowling Green, Ohio, United States
Toledo Clinic - Oregon
🇺🇸Oregon, Ohio, United States
St. Charles Mercy Hospital
🇺🇸Oregon, Ohio, United States
Mercy Hospital of Tiffin
🇺🇸Tiffin, Ohio, United States
Flower Hospital Cancer Center
🇺🇸Sylvania, Ohio, United States
Toledo Hospital
🇺🇸Toledo, Ohio, United States
Medical University of Ohio Cancer Center
🇺🇸Toledo, Ohio, United States
St. Vincent Mercy Medical Center
🇺🇸Toledo, Ohio, United States
St. Anne Mercy Hospital
🇺🇸Toledo, Ohio, United States
CCOP - Toledo Community Hospital
🇺🇸Toledo, Ohio, United States
Fulton County Health Center
🇺🇸Wauseon, Ohio, United States
Toledo Clinic, Incorporated - Main Clinic
🇺🇸Toledo, Ohio, United States
Fredericksburg Oncology, Incorporated
🇺🇸Fredericksburg, Virginia, United States
Marshfield Clinic - Wisconsin Rapids Center
🇺🇸Wisconsin Rapids, Wisconsin, United States
Center for Cancer Treatment & Prevention at Sacred Heart Hospital
🇺🇸Eau Claire, Wisconsin, United States
Marshfield Clinic - Chippewa Center
🇺🇸Chippewa Falls, Wisconsin, United States
Marshfield Clinic Cancer Care at Regional Cancer Center
🇺🇸Eau Claire, Wisconsin, United States
Marshfield Clinic - Ladysmith Center
🇺🇸Ladysmith, Wisconsin, United States
Marshfield Clinic at Saint Michael's Hospital
🇺🇸Stevens Point, Wisconsin, United States
Virginia Piper Cancer Institute at Abbott - Northwestern Hospital
🇺🇸Minneapolis, Minnesota, United States
Mercy and Unity Cancer Center at Unity Hospital
🇺🇸Fridley, Minnesota, United States
Sanford Clinic North-Fargo
🇺🇸Fargo, North Dakota, United States
Roger Maris Cancer Center at MeritCare Hospital
🇺🇸Fargo, North Dakota, United States
CCOP - MeritCare Hospital
🇺🇸Fargo, North Dakota, United States
Minnesota Oncology - Woodbury
🇺🇸Woodbury, Minnesota, United States
MeritCare Bemidji
🇺🇸Bemidji, Minnesota, United States
Mercy and Unity Cancer Center at Mercy Hospital
🇺🇸Coon Rapids, Minnesota, United States
Humphrey Cancer Center at North Memorial Outpatient Center
🇺🇸Robbinsdale, Minnesota, United States
Fairview Southdale Hospital
🇺🇸Edina, Minnesota, United States
MeritCare Broadway
🇺🇸Fargo, North Dakota, United States
Lakeview Hospital
🇺🇸Stillwater, Minnesota, United States
St. Francis Cancer Center at St. Francis Medical Center
🇺🇸Shakopee, Minnesota, United States
Sanford Medical Center-Fargo
🇺🇸Fargo, North Dakota, United States
Saint Joseph Mercy Cancer Center
🇺🇸Ann Arbor, Michigan, United States
Saint John Hospital and Medical Center
🇺🇸Detroit, Michigan, United States
Mayo Clinic Cancer Center
🇺🇸Rochester, Minnesota, United States
Creighton University Medical Center
🇺🇸Omaha, Nebraska, United States
CCOP - Missouri Valley Cancer Consortium
🇺🇸Omaha, Nebraska, United States
Lakeside Hospital
🇺🇸Omaha, Nebraska, United States
Immanuel Medical Center
🇺🇸Omaha, Nebraska, United States
Alegant Health Cancer Center at Bergan Mercy Medical Center
🇺🇸Omaha, Nebraska, United States
MBCCOP - Medical College of Georgia Cancer Center
🇺🇸Augusta, Georgia, United States
CCOP - Carle Cancer Center
🇺🇸Urbana, Illinois, United States
Elkhart Clinic, LLC
🇺🇸Elkhart, Indiana, United States
Mayo Clinic Scottsdale
🇺🇸Scottsdale, Arizona, United States
Elkhart General Hospital
🇺🇸Elkhart, Indiana, United States
Mayo Clinic - Jacksonville
🇺🇸Jacksonville, Florida, United States
CCOP - Northern Indiana CR Consortium
🇺🇸South Bend, Indiana, United States
Michiana Hematology Oncology PC-Mishawaka
🇺🇸Mishawaka, Indiana, United States
Memorial Hospital of South Bend
🇺🇸South Bend, Indiana, United States
Hickman Cancer Center at Bixby Medical Center
🇺🇸Adrian, Michigan, United States
Genesys Hurley Cancer Institute
🇺🇸Flint, Michigan, United States
Boston University Cancer Research Center
🇺🇸Boston, Massachusetts, United States
CCOP - Michigan Cancer Research Consortium
🇺🇸Ann Arbor, Michigan, United States
Mecosta County Medical Center
🇺🇸Big Rapids, Michigan, United States
Mercy Regional Cancer Center at Mercy Hospital
🇺🇸Port Huron, Michigan, United States
Munson Medical Center
🇺🇸Traverse City, Michigan, United States
Sanford Clinic North-Bemidgi
🇺🇸Bemidji, Minnesota, United States
Minnesota Oncology - Maplewood
🇺🇸Maplewood, Minnesota, United States
New Ulm Medical Center
🇺🇸New Ulm, Minnesota, United States
Hennepin County Medical Center - Minneapolis
🇺🇸Minneapolis, Minnesota, United States
Community Cancer Center
🇺🇸Elyria, Ohio, United States
Hematology Oncology Center
🇺🇸Elyria, Ohio, United States
Fairview Ridges Hospital
🇺🇸Burnsville, Minnesota, United States
Cedar Rapids Oncology Associates
🇺🇸Cedar Rapids, Iowa, United States
Michiana Hematology-Oncology, PC - South Bend
🇺🇸Mishawaka, Indiana, United States
Oakwood Cancer Center at Oakwood Hospital and Medical Center
🇺🇸Dearborn, Michigan, United States
Indiana University Health La Porte Hospital
🇺🇸La Porte, Indiana, United States