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

NCT ID: NCT01156142

Last Updated: 2017-08-09

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

155 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-12-31

Study Completion Date

2015-03-02

Brief Summary

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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

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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.

Conditions

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Head and Neck Cancer Mucositis Oral Complications of Radiation Therapy Pain

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

SUPPORTIVE_CARE

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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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.

Group Type EXPERIMENTAL

doxepin hydrochloride

Intervention Type DRUG

Oral rinse

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.

Group Type PLACEBO_COMPARATOR

placebo

Intervention Type OTHER

Oral rinse

Interventions

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doxepin hydrochloride

Oral rinse

Intervention Type DRUG

placebo

Oral rinse

Intervention Type OTHER

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Alliance for Clinical Trials in Oncology

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Robert C. Miller, MD

Role: STUDY_CHAIR

Mayo Clinic

Locations

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Mayo Clinic Scottsdale

Scottsdale, Arizona, United States

Site Status

Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center

Hartford, Connecticut, United States

Site Status

Mayo Clinic - Jacksonville

Jacksonville, Florida, United States

Site Status

MBCCOP - Medical College of Georgia Cancer Center

Augusta, Georgia, United States

Site Status

Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical Center

Boise, Idaho, United States

Site Status

CCOP - Carle Cancer Center

Urbana, Illinois, United States

Site Status

Elkhart Clinic, LLC

Elkhart, Indiana, United States

Site Status

Michiana Hematology-Oncology, PC - Elkhart

Elkhart, Indiana, United States

Site Status

Elkhart General Hospital

Elkhart, Indiana, United States

Site Status

Howard Community Hospital

Kokomo, Indiana, United States

Site Status

Center for Cancer Therapy at LaPorte Hospital and Health Services

La Porte, Indiana, United States

Site Status

Indiana University Health La Porte Hospital

La Porte, Indiana, United States

Site Status

Michiana Hematology-Oncology, PC - South Bend

Mishawaka, Indiana, United States

Site Status

Saint Joseph Regional Medical Center

Mishawaka, Indiana, United States

Site Status

Michiana Hematology Oncology PC-Mishawaka

Mishawaka, Indiana, United States

Site Status

Michiana Hematology Oncology PC - Plymouth

Plymouth, Indiana, United States

Site Status

CCOP - Northern Indiana CR Consortium

South Bend, Indiana, United States

Site Status

Memorial Hospital of South Bend

South Bend, Indiana, United States

Site Status

Michiana Hematology Oncology PC - La Porte

Westville, Indiana, United States

Site Status

McFarland Clinic, PC

Ames, Iowa, United States

Site Status

Cedar Rapids Oncology Associates

Cedar Rapids, Iowa, United States

Site Status

Mercy Regional Cancer Center at Mercy Medical Center

Cedar Rapids, Iowa, United States

Site Status

Boston University Cancer Research Center

Boston, Massachusetts, United States

Site Status

Hickman Cancer Center at Bixby Medical Center

Adrian, Michigan, United States

Site Status

Saint Joseph Mercy Cancer Center

Ann Arbor, Michigan, United States

Site Status

CCOP - Michigan Cancer Research Consortium

Ann Arbor, Michigan, United States

Site Status

Battle Creek Health System Cancer Care Center

Battle Creek, Michigan, United States

Site Status

Mecosta County Medical Center

Big Rapids, Michigan, United States

Site Status

Oakwood Cancer Center at Oakwood Hospital and Medical Center

Dearborn, Michigan, United States

Site Status

Saint John Hospital and Medical Center

Detroit, Michigan, United States

Site Status

Genesys Hurley Cancer Institute

Flint, Michigan, United States

Site Status

Hurley Medical Center

Flint, Michigan, United States

Site Status

Genesys Regional Medical Center

Grand Blanc, Michigan, United States

Site Status

Butterworth Hospital at Spectrum Health

Grand Rapids, Michigan, United States

Site Status

CCOP - Grand Rapids

Grand Rapids, Michigan, United States

Site Status

Lacks Cancer Center at Saint Mary's Health Care

Grand Rapids, Michigan, United States

Site Status

Van Elslander Cancer Center at St. John Hospital and Medical Center

Grosse Pointe Woods, Michigan, United States

Site Status

Allegiance Health

Jackson, Michigan, United States

Site Status

Foote Memorial Hospital

Jackson, Michigan, United States

Site Status

Sparrow Regional Cancer Center

Lansing, Michigan, United States

Site Status

St. Mary Mercy Hospital

Livonia, Michigan, United States

Site Status

Community Cancer Center of Monroe

Monroe, Michigan, United States

Site Status

Mercy Memorial Hospital - Monroe

Monroe, Michigan, United States

Site Status

Mercy General Health Partners

Muskegon, Michigan, United States

Site Status

St. Joseph Mercy Oakland

Pontiac, Michigan, United States

Site Status

Mercy Regional Cancer Center at Mercy Hospital

Port Huron, Michigan, United States

Site Status

Seton Cancer Institute at Saint Mary's - Saginaw

Saginaw, Michigan, United States

Site Status

Lakeland Regional Cancer Care Center - St. Joseph

Saint Joseph, Michigan, United States

Site Status

Lakeside Cancer Specialists, PLLC

Saint Joseph, Michigan, United States

Site Status

Marie Yeager Cancer Center

Saint Joseph, Michigan, United States

Site Status

Munson Medical Center

Traverse City, Michigan, United States

Site Status

St. John Macomb Hospital

Warren, Michigan, United States

Site Status

MeritCare Bemidji

Bemidji, Minnesota, United States

Site Status

Sanford Clinic North-Bemidgi

Bemidji, Minnesota, United States

Site Status

Fairview Ridges Hospital

Burnsville, Minnesota, United States

Site Status

Mercy and Unity Cancer Center at Mercy Hospital

Coon Rapids, Minnesota, United States

Site Status

Fairview Southdale Hospital

Edina, Minnesota, United States

Site Status

Mercy and Unity Cancer Center at Unity Hospital

Fridley, Minnesota, United States

Site Status

Hutchinson Area Health Care

Hutchinson, Minnesota, United States

Site Status

HealthEast Cancer Care at St. John's Hospital

Maplewood, Minnesota, United States

Site Status

Minnesota Oncology - Maplewood

Maplewood, Minnesota, United States

Site Status

Virginia Piper Cancer Institute at Abbott - Northwestern Hospital

Minneapolis, Minnesota, United States

Site Status

Hennepin County Medical Center - Minneapolis

Minneapolis, Minnesota, United States

Site Status

New Ulm Medical Center

New Ulm, Minnesota, United States

Site Status

Humphrey Cancer Center at North Memorial Outpatient Center

Robbinsdale, Minnesota, United States

Site Status

Mayo Clinic Cancer Center

Rochester, Minnesota, United States

Site Status

CCOP - Metro-Minnesota

Saint Louis Park, Minnesota, United States

Site Status

Park Nicollet Cancer Center

Saint Louis Park, Minnesota, United States

Site Status

Regions Hospital Cancer Care Center

Saint Paul, Minnesota, United States

Site Status

United Hospital

Saint Paul, Minnesota, United States

Site Status

St. Francis Cancer Center at St. Francis Medical Center

Shakopee, Minnesota, United States

Site Status

Lakeview Hospital

Stillwater, Minnesota, United States

Site Status

Ridgeview Medical Center

Waconia, Minnesota, United States

Site Status

Willmar Cancer Center at Rice Memorial Hospital

Willmar, Minnesota, United States

Site Status

Minnesota Oncology - Woodbury

Woodbury, Minnesota, United States

Site Status

Cancer Resource Center - Lincoln

Lincoln, Nebraska, United States

Site Status

CCOP - Missouri Valley Cancer Consortium

Omaha, Nebraska, United States

Site Status

Immanuel Medical Center

Omaha, Nebraska, United States

Site Status

Alegant Health Cancer Center at Bergan Mercy Medical Center

Omaha, Nebraska, United States

Site Status

Lakeside Hospital

Omaha, Nebraska, United States

Site Status

Creighton University Medical Center

Omaha, Nebraska, United States

Site Status

MeritCare Broadway

Fargo, North Dakota, United States

Site Status

Sanford Clinic North-Fargo

Fargo, North Dakota, United States

Site Status

CCOP - MeritCare Hospital

Fargo, North Dakota, United States

Site Status

Roger Maris Cancer Center at MeritCare Hospital

Fargo, North Dakota, United States

Site Status

Sanford Medical Center-Fargo

Fargo, North Dakota, United States

Site Status

Altru Cancer Center at Altru Hospital

Grand Forks, North Dakota, United States

Site Status

Wood County Oncology Center

Bowling Green, Ohio, United States

Site Status

Community Cancer Center

Elyria, Ohio, United States

Site Status

Hematology Oncology Center

Elyria, Ohio, United States

Site Status

Lima Memorial Hospital

Lima, Ohio, United States

Site Status

Northwest Ohio Oncology Center

Maumee, Ohio, United States

Site Status

St. Charles Mercy Hospital

Oregon, Ohio, United States

Site Status

Toledo Clinic - Oregon

Oregon, Ohio, United States

Site Status

Flower Hospital Cancer Center

Sylvania, Ohio, United States

Site Status

Mercy Hospital of Tiffin

Tiffin, Ohio, United States

Site Status

Toledo Hospital

Toledo, Ohio, United States

Site Status

St. Vincent Mercy Medical Center

Toledo, Ohio, United States

Site Status

Medical University of Ohio Cancer Center

Toledo, Ohio, United States

Site Status

CCOP - Toledo Community Hospital

Toledo, Ohio, United States

Site Status

St. Anne Mercy Hospital

Toledo, Ohio, United States

Site Status

Toledo Clinic, Incorporated - Main Clinic

Toledo, Ohio, United States

Site Status

Fulton County Health Center

Wauseon, Ohio, United States

Site Status

Fredericksburg Oncology, Incorporated

Fredericksburg, Virginia, United States

Site Status

Marshfield Clinic - Chippewa Center

Chippewa Falls, Wisconsin, United States

Site Status

Center for Cancer Treatment & Prevention at Sacred Heart Hospital

Eau Claire, Wisconsin, United States

Site Status

Marshfield Clinic Cancer Care at Regional Cancer Center

Eau Claire, Wisconsin, United States

Site Status

Marshfield Clinic - Ladysmith Center

Ladysmith, Wisconsin, United States

Site Status

Marshfield Clinic - Marshfield Center

Marshfield, Wisconsin, United States

Site Status

Saint Joseph's Hospital

Marshfield, Wisconsin, United States

Site Status

Marshfield Clinic - Lakeland Center

Minocqua, Wisconsin, United States

Site Status

Ministry Medical Group at Saint Mary's Hospital

Rhinelander, Wisconsin, United States

Site Status

Marshfield Clinic - Indianhead Center

Rice Lake, Wisconsin, United States

Site Status

Marshfield Clinic at Saint Michael's Hospital

Stevens Point, Wisconsin, United States

Site Status

Saint Michael's Hospital Cancer Center

Stevens Point, Wisconsin, United States

Site Status

Marshfield Clinic - Wausau Center

Wausau, Wisconsin, United States

Site Status

Diagnostic and Treatment Center

Weston, Wisconsin, United States

Site Status

Marshfield Clinic - Weston Center

Weston, Wisconsin, United States

Site Status

Ministry Saint Clare's Hospital

Weston, Wisconsin, United States

Site Status

Marshfield Clinic - Wisconsin Rapids Center

Wisconsin Rapids, Wisconsin, United States

Site Status

Countries

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United States

References

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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.

Reference Type DERIVED
PMID: 24733799 (View on PubMed)

Other Identifiers

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NCI-2011-02049

Identifier Type: REGISTRY

Identifier Source: secondary_id

CDR0000675520

Identifier Type: REGISTRY

Identifier Source: secondary_id

U10CA037404

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCCTG-N09C6

Identifier Type: -

Identifier Source: org_study_id

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