Doxepin Hydrochloride in Treating Oral Mucositis Pain in Patients With Head and Neck Cancer Undergoing Radiation Therapy With or Without Chemotherapy

Condition(s) targeted: Head and Neck Cancer; Mucositis; Oral Complications of Radiation Therapy; Pain

Intervention: doxepin hydrochloride (Drug); placebo (Other)

Phase: Phase 3

Status: Active, not recruiting

Sponsored by: Alliance for Clinical Trials in Oncology

Official(s) and/or principal investigator(s):
Robert C. Miller, MD, Study Chair, Affiliation: Mayo Clinic

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.

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

Study design: Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Supportive Care

Primary outcome: Total pain reduction (mouth and throat)

Secondary outcome:

Total taste of the oral rinse

Total stinging or burning from the oral rinse

Total drowsiness increase

Incidence of using alternative analgesics 4 hours before and in between study medications

Patient preference for continuing therapy with oral doxepin hydrochloride

Pain reduction and other adverse event profile in the blinded cross-over phase

Long-term outcome of doxepin hydrochloride oral rinse for patient continued therapy

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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria: 1. ≥ 18 years of age 2. 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. 3. ≥ 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. 4. Ability to complete questionnaire(s) independently or with assistance 5. ECOG Performance Status 0, 1 or 2. 6. Provide informed written consent. 7. Willingness to return to enrolling institution for follow-up. Exclusion Criteria: 1. Known allergy to doxepin, tricyclic antidepressants, or any known component of the drug formulation 2. Use of a tricyclic antidepressant or monoamine oxidase inhibitor within the 2 weeks prior to registration 3. Current untreated or unresolved oral candidiasis or oral HSV infection 4. Current untreated narrow angle glaucoma 5. Current untreated urinary retention ≤ 6 weeks prior to registration 6. 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 7. 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

Mayo Clinic Scottsdale, Scottsdale, Arizona 85259-5499, United States

Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center, Hartford, Connecticut 06105, United States

Mayo Clinic - Jacksonville, Jacksonville, Florida 32224, United States

MBCCOP - Medical College of Georgia Cancer Center, Augusta, Georgia 30912, United States

Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical Center, Boise, Idaho 83706, United States

CCOP - Carle Cancer Center, Urbana, Illinois 61801, United States

Elkhart Clinic, LLC, Elkhart, Indiana 46514-2098, United States

Elkhart General Hospital, Elkhart, Indiana 46515, United States

Michiana Hematology-Oncology, PC - Elkhart, Elkhart, Indiana 46514, United States

Howard Community Hospital, Kokomo, Indiana 46904, United States

Center for Cancer Therapy at LaPorte Hospital and Health Services, La Porte, Indiana 46350, United States

Indiana University Health La Porte Hospital, La Porte, Indiana 46350, United States

Michiana Hematology Oncology PC-Mishawaka, Mishawaka, Indiana 46545, United States

Michiana Hematology-Oncology, PC - South Bend, Mishawaka, Indiana 46545-1470, United States

Saint Joseph Regional Medical Center, Mishawaka, Indiana 46545-1470, United States

Michiana Hematology Oncology PC - Plymouth, Plymouth, Indiana 46563, United States

CCOP - Northern Indiana CR Consortium, South Bend, Indiana 46601, United States

Memorial Hospital of South Bend, South Bend, Indiana 46601, United States

Michiana Hematology Oncology PC - La Porte, Westville, Indiana 46391, United States

McFarland Clinic, PC, Ames, Iowa 50010, United States

Cedar Rapids Oncology Associates, Cedar Rapids, Iowa 52403, United States

Mercy Regional Cancer Center at Mercy Medical Center, Cedar Rapids, Iowa 52403, United States

Boston University Cancer Research Center, Boston, Massachusetts 02118, United States

Hickman Cancer Center at Bixby Medical Center, Adrian, Michigan 49221, United States

CCOP - Michigan Cancer Research Consortium, Ann Arbor, Michigan 48106, United States

Saint Joseph Mercy Cancer Center, Ann Arbor, Michigan 48106-0995, United States

Battle Creek Health System Cancer Care Center, Battle Creek, Michigan 49017, United States

Mecosta County Medical Center, Big Rapids, Michigan 49307, United States

Oakwood Cancer Center at Oakwood Hospital and Medical Center, Dearborn, Michigan 48123-2500, United States

Saint John Hospital and Medical Center, Detroit, Michigan 48236, United States

Genesys Hurley Cancer Institute, Flint, Michigan 48503, United States

Hurley Medical Center, Flint, Michigan 48503, United States

Genesys Regional Medical Center, Grand Blanc, Michigan 48439, United States

Butterworth Hospital at Spectrum Health, Grand Rapids, Michigan 49503, United States

CCOP - Grand Rapids, Grand Rapids, Michigan 49503, United States

Lacks Cancer Center at Saint Mary's Health Care, Grand Rapids, Michigan 49503, United States

Van Elslander Cancer Center at St. John Hospital and Medical Center, Grosse Pointe Woods, Michigan 48236, United States

Allegiance Health, Jackson, Michigan 49201, United States

Foote Memorial Hospital, Jackson, Michigan 49201, United States

Sparrow Regional Cancer Center, Lansing, Michigan 48912-1811, United States

St. Mary Mercy Hospital, Livonia, Michigan 48154, United States

Community Cancer Center of Monroe, Monroe, Michigan 48162, United States

Mercy Memorial Hospital - Monroe, Monroe, Michigan 48162, United States

Mercy General Health Partners, Muskegon, Michigan 49444, United States

St. Joseph Mercy Oakland, Pontiac, Michigan 48341-2985, United States

Mercy Regional Cancer Center at Mercy Hospital, Port Huron, Michigan 48060, United States

Seton Cancer Institute at Saint Mary's - Saginaw, Saginaw, Michigan 48601, United States

Lakeland Regional Cancer Care Center - St. Joseph, Saint Joseph, Michigan 49085, United States

Lakeside Cancer Specialists, PLLC, Saint Joseph, Michigan 49085, United States

Marie Yeager Cancer Center, Saint Joseph, Michigan 49085, United States

Munson Medical Center, Traverse City, Michigan 49684, United States

St. John Macomb Hospital, Warren, Michigan 48093, United States

MeritCare Bemidji, Bemidji, Minnesota 56601, United States

Sanford Clinic North-Bemidgi, Bemidji, Minnesota 56601, United States

Fairview Ridges Hospital, Burnsville, Minnesota 55337, United States

Mercy and Unity Cancer Center at Mercy Hospital, Coon Rapids, Minnesota 55433, United States

Fairview Southdale Hospital, Edina, Minnesota 55435, United States

Mercy and Unity Cancer Center at Unity Hospital, Fridley, Minnesota 55432, United States

Hutchinson Area Health Care, Hutchinson, Minnesota 55350, United States

HealthEast Cancer Care at St. John's Hospital, Maplewood, Minnesota 55109, United States

Minnesota Oncology - Maplewood, Maplewood, Minnesota 55109, United States

Hennepin County Medical Center - Minneapolis, Minneapolis, Minnesota 55415, United States

Virginia Piper Cancer Institute at Abbott - Northwestern Hospital, Minneapolis, Minnesota 55407, United States

New Ulm Medical Center, New Ulm, Minnesota 56073, United States

Humphrey Cancer Center at North Memorial Outpatient Center, Robbinsdale, Minnesota 55422-2900, United States

Mayo Clinic Cancer Center, Rochester, Minnesota 55905, United States

CCOP - Metro-Minnesota, Saint Louis Park, Minnesota 55416, United States

Park Nicollet Cancer Center, Saint Louis Park, Minnesota 55416, United States

United Hospital, Saint Paul, Minnesota 55102, United States

St. Francis Cancer Center at St. Francis Medical Center, Shakopee, Minnesota 55379, United States

Regions Hospital Cancer Care Center, St. Paul, Minnesota 55101, United States

Lakeview Hospital, Stillwater, Minnesota 55082, United States

Ridgeview Medical Center, Waconia, Minnesota 55387, United States

Willmar Cancer Center at Rice Memorial Hospital, Willmar, Minnesota 56201, United States

Minnesota Oncology - Woodbury, Woodbury, Minnesota 55125, United States

Cancer Resource Center - Lincoln, Lincoln, Nebraska 68510, United States

Alegant Health Cancer Center at Bergan Mercy Medical Center, Omaha, Nebraska 68124, United States

CCOP - Missouri Valley Cancer Consortium, Omaha, Nebraska 68106, United States

Creighton University Medical Center, Omaha, Nebraska 68131-2197, United States

Immanuel Medical Center, Omaha, Nebraska 68122, United States

Lakeside Hospital, Omaha, Nebraska 68130, United States

CCOP - MeritCare Hospital, Fargo, North Dakota 58122, United States

MeritCare Broadway, Fargo, North Dakota 58102, United States

Roger Maris Cancer Center at MeritCare Hospital, Fargo, North Dakota 58122, United States

Sanford Clinic North-Fargo, Fargo, North Dakota 58102, United States

Sanford Medical Center-Fargo, Fargo, North Dakota 58122, United States

Altru Cancer Center at Altru Hospital, Grand Forks, North Dakota 58201, United States

Wood County Oncology Center, Bowling Green, Ohio 43402, United States

Community Cancer Center, Elyria, Ohio 44035, United States

Hematology Oncology Center, Elyria, Ohio 44035, United States

Lima Memorial Hospital, Lima, Ohio 45804, United States

Northwest Ohio Oncology Center, Maumee, Ohio 43537-1839, United States

St. Charles Mercy Hospital, Oregon, Ohio 43616, United States

Toledo Clinic - Oregon, Oregon, Ohio 43616, United States

Flower Hospital Cancer Center, Sylvania, Ohio 43560, United States

Mercy Hospital of Tiffin, Tiffin, Ohio 44883, United States

CCOP - Toledo Community Hospital, Toledo, Ohio 43617, United States

Medical University of Ohio Cancer Center, Toledo, Ohio 43614, United States

St. Anne Mercy Hospital, Toledo, Ohio 43623, United States

St. Vincent Mercy Medical Center, Toledo, Ohio 43608, United States

Toledo Clinic, Incorporated - Main Clinic, Toledo, Ohio 43623, United States

Toledo Hospital, Toledo, Ohio 43606, United States

Fulton County Health Center, Wauseon, Ohio 43567, United States

Fredericksburg Oncology, Incorporated, Fredericksburg, Virginia 22401, United States

Marshfield Clinic - Chippewa Center, Chippewa Falls, Wisconsin 54729, United States

Center for Cancer Treatment & Prevention at Sacred Heart Hospital, Eau Claire, Wisconsin 54701, United States

Marshfield Clinic Cancer Care at Regional Cancer Center, Eau Claire, Wisconsin 54701, United States

Marshfield Clinic - Ladysmith Center, Ladysmith, Wisconsin 54848, United States

Marshfield Clinic - Marshfield Center, Marshfield, Wisconsin 54449, United States

Saint Joseph's Hospital, Marshfield, Wisconsin 54449, United States

Marshfield Clinic - Lakeland Center, Minocqua, Wisconsin 54548, United States

Ministry Medical Group at Saint Mary's Hospital, Rhinelander, Wisconsin 54501, United States

Marshfield Clinic - Indianhead Center, Rice Lake, Wisconsin 54868, United States

Marshfield Clinic at Saint Michael's Hospital, Stevens Point, Wisconsin 54481, United States

Saint Michael's Hospital Cancer Center, Stevens Point, Wisconsin 54481, United States

Marshfield Clinic - Wausau Center, Wausau, Wisconsin 54401, United States

Diagnostic and Treatment Center, Weston, Wisconsin 54476, United States

Marshfield Clinic - Weston Center, Weston, Wisconsin 54476, United States

Ministry Saint Clare's Hospital, Weston, Wisconsin 54476, United States

Marshfield Clinic - Wisconsin Rapids Center, Wisconsin Rapids, Wisconsin 54494, United States

Clinical trial summary from the National Cancer Institute's PDQ® database

Starting date: December 2010
Last updated: July 30, 2015