NCT01156142

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
155

participants targeted

Target at P25-P50 for phase_3 head-and-neck-cancer

Timeline
Completed

Started Dec 2010

Geographic Reach
1 country

120 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 1, 2010

Completed
1 day until next milestone

First Posted

Study publicly available on registry

July 2, 2010

Completed
5 months until next milestone

Study Start

First participant enrolled

December 1, 2010

Completed
1.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2012

Completed
2.8 years until next milestone

Study Completion

Last participant's last visit for all outcomes

March 2, 2015

Completed
2.2 years until next milestone

Results Posted

Study results publicly available

May 8, 2017

Completed
Last Updated

August 9, 2017

Status Verified

July 1, 2017

Enrollment Period

1.4 years

First QC Date

July 1, 2010

Results QC Date

December 12, 2016

Last Update Submit

July 11, 2017

Conditions

Keywords

oral complications of radiation therapymucositispainstage I squamous cell carcinoma of the paranasal sinus and nasal cavityrecurrent squamous cell carcinoma of the hypopharynxsquamous cell carcinoma of the hypopharynxrecurrent squamous cell carcinoma of the larynxrecurrent verrucous carcinoma of the larynxsquamous cell carcinoma of the larynxverrucous carcinoma of the larynxrecurrent adenoid cystic carcinoma of the oral cavityrecurrent mucoepidermoid carcinoma of the oral cavityrecurrent verrucous carcinoma of the oral cavityadenoid cystic carcinoma of the oral cavitymucoepidermoid carcinoma of the oral cavityverrucous carcinoma of the oral cavitysquamous cell carcinoma of the lip and oral cavityrecurrent basal cell carcinoma of the liprecurrent squamous cell carcinoma of the lip and oral cavitybasal cell carcinoma of the lipmetastatic squamous neck cancer with occult primary squamous cell carcinomarecurrent metastatic squamous neck cancer with occult primaryuntreated metastatic squamous neck cancer with occult primaryrecurrent lymphoepithelioma of the nasopharynxrecurrent squamous cell carcinoma of the nasopharynxlymphoepithelioma of the nasopharynxsquamous cell carcinoma of the nasopharynxrecurrent lymphoepithelioma of the oropharynxrecurrent squamous cell carcinoma of the oropharynxlymphoepithelioma of the oropharynxsquamous cell carcinoma of the oropharynxrecurrent esthesioneuroblastoma of the paranasal sinus and nasal cavityrecurrent inverted papilloma of the paranasal sinus and nasal cavityrecurrent midline lethal granuloma of the paranasal sinus and nasal cavityrecurrent squamous cell carcinoma of the paranasal sinus and nasal cavityesthesioneuroblastoma of the paranasal sinus and nasal cavityinverted papilloma of the paranasal sinus and nasal cavitymidline lethal granuloma of the paranasal sinus and nasal cavitysquamous cell carcinoma of the paranasal sinus and nasal cavityhigh-grade salivary gland mucoepidermoid carcinomalow-grade salivary gland mucoepidermoid carcinomarecurrent salivary gland cancersalivary gland acinic cell tumorsalivary gland adenocarcinomasalivary gland adenoid cystic carcinomasalivary gland anaplastic carcinomasalivary gland malignant mixed cell type tumorsalivary gland poorly differentiated carcinomasalivary gland squamous cell carcinomasalivary gland cancertongue cancer

Outcome Measures

Primary Outcomes (1)

  • 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.

    Baseline and Day 1

Secondary Outcomes (5)

  • Total Taste of the Oral Rinse

    Up to 9 days

  • Total Stinging or Burning From the Oral Rinse

    Up to 9 days

  • Total Drowsiness Increase

    Up to 9 days

  • Incidence of Using Alternative Analgesics Between 2 and 4 Hours After the Initial Mouthwash

    Up to 9 days

  • Patient Preference for Continuing Therapy With Oral Doxepin Hydrochloride

    Up to 9 days

Study Arms (2)

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.

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.

Other: placebo

Interventions

Oral rinse

Arm I
placeboOTHER

Oral rinse

Arm II

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • ≥ 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.

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (120)

Mayo Clinic Scottsdale

Scottsdale, Arizona, 85259-5499, United States

Location

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

Hartford, Connecticut, 06105, United States

Location

Mayo Clinic - Jacksonville

Jacksonville, Florida, 32224, United States

Location

MBCCOP - Medical College of Georgia Cancer Center

Augusta, Georgia, 30912, United States

Location

Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical Center

Boise, Idaho, 83706, United States

Location

CCOP - Carle Cancer Center

Urbana, Illinois, 61801, United States

Location

Elkhart Clinic, LLC

Elkhart, Indiana, 46514-2098, United States

Location

Michiana Hematology-Oncology, PC - Elkhart

Elkhart, Indiana, 46514, United States

Location

Elkhart General Hospital

Elkhart, Indiana, 46515, United States

Location

Howard Community Hospital

Kokomo, Indiana, 46904, United States

Location

Center for Cancer Therapy at LaPorte Hospital and Health Services

La Porte, Indiana, 46350, United States

Location

Indiana University Health La Porte Hospital

La Porte, Indiana, 46350, United States

Location

Michiana Hematology-Oncology, PC - South Bend

Mishawaka, Indiana, 46545-1470, United States

Location

Saint Joseph Regional Medical Center

Mishawaka, Indiana, 46545-1470, United States

Location

Michiana Hematology Oncology PC-Mishawaka

Mishawaka, Indiana, 46545, United States

Location

Michiana Hematology Oncology PC - Plymouth

Plymouth, Indiana, 46563, United States

Location

CCOP - Northern Indiana CR Consortium

South Bend, Indiana, 46601, United States

Location

Memorial Hospital of South Bend

South Bend, Indiana, 46601, United States

Location

Michiana Hematology Oncology PC - La Porte

Westville, Indiana, 46391, United States

Location

McFarland Clinic, PC

Ames, Iowa, 50010, United States

Location

Cedar Rapids Oncology Associates

Cedar Rapids, Iowa, 52403, United States

Location

Mercy Regional Cancer Center at Mercy Medical Center

Cedar Rapids, Iowa, 52403, United States

Location

Boston University Cancer Research Center

Boston, Massachusetts, 02118, United States

Location

Hickman Cancer Center at Bixby Medical Center

Adrian, Michigan, 49221, United States

Location

Saint Joseph Mercy Cancer Center

Ann Arbor, Michigan, 48106-0995, United States

Location

CCOP - Michigan Cancer Research Consortium

Ann Arbor, Michigan, 48106, United States

Location

Battle Creek Health System Cancer Care Center

Battle Creek, Michigan, 49017, United States

Location

Mecosta County Medical Center

Big Rapids, Michigan, 49307, United States

Location

Oakwood Cancer Center at Oakwood Hospital and Medical Center

Dearborn, Michigan, 48123-2500, United States

Location

Saint John Hospital and Medical Center

Detroit, Michigan, 48236, United States

Location

Genesys Hurley Cancer Institute

Flint, Michigan, 48503, United States

Location

Hurley Medical Center

Flint, Michigan, 48503, United States

Location

Genesys Regional Medical Center

Grand Blanc, Michigan, 48439, United States

Location

Butterworth Hospital at Spectrum Health

Grand Rapids, Michigan, 49503, United States

Location

CCOP - Grand Rapids

Grand Rapids, Michigan, 49503, United States

Location

Lacks Cancer Center at Saint Mary's Health Care

Grand Rapids, Michigan, 49503, United States

Location

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

Grosse Pointe Woods, Michigan, 48236, United States

Location

Allegiance Health

Jackson, Michigan, 49201, United States

Location

Foote Memorial Hospital

Jackson, Michigan, 49201, United States

Location

Sparrow Regional Cancer Center

Lansing, Michigan, 48912-1811, United States

Location

St. Mary Mercy Hospital

Livonia, Michigan, 48154, United States

Location

Community Cancer Center of Monroe

Monroe, Michigan, 48162, United States

Location

Mercy Memorial Hospital - Monroe

Monroe, Michigan, 48162, United States

Location

Mercy General Health Partners

Muskegon, Michigan, 49444, United States

Location

St. Joseph Mercy Oakland

Pontiac, Michigan, 48341-2985, United States

Location

Mercy Regional Cancer Center at Mercy Hospital

Port Huron, Michigan, 48060, United States

Location

Seton Cancer Institute at Saint Mary's - Saginaw

Saginaw, Michigan, 48601, United States

Location

Lakeland Regional Cancer Care Center - St. Joseph

Saint Joseph, Michigan, 49085, United States

Location

Lakeside Cancer Specialists, PLLC

Saint Joseph, Michigan, 49085, United States

Location

Marie Yeager Cancer Center

Saint Joseph, Michigan, 49085, United States

Location

Munson Medical Center

Traverse City, Michigan, 49684, United States

Location

St. John Macomb Hospital

Warren, Michigan, 48093, United States

Location

MeritCare Bemidji

Bemidji, Minnesota, 56601, United States

Location

Sanford Clinic North-Bemidgi

Bemidji, Minnesota, 56601, United States

Location

Fairview Ridges Hospital

Burnsville, Minnesota, 55337, United States

Location

Mercy and Unity Cancer Center at Mercy Hospital

Coon Rapids, Minnesota, 55433, United States

Location

Fairview Southdale Hospital

Edina, Minnesota, 55435, United States

Location

Mercy and Unity Cancer Center at Unity Hospital

Fridley, Minnesota, 55432, United States

Location

Hutchinson Area Health Care

Hutchinson, Minnesota, 55350, United States

Location

HealthEast Cancer Care at St. John's Hospital

Maplewood, Minnesota, 55109, United States

Location

Minnesota Oncology - Maplewood

Maplewood, Minnesota, 55109, United States

Location

Virginia Piper Cancer Institute at Abbott - Northwestern Hospital

Minneapolis, Minnesota, 55407, United States

Location

Hennepin County Medical Center - Minneapolis

Minneapolis, Minnesota, 55415, United States

Location

New Ulm Medical Center

New Ulm, Minnesota, 56073, United States

Location

Humphrey Cancer Center at North Memorial Outpatient Center

Robbinsdale, Minnesota, 55422-2900, United States

Location

Mayo Clinic Cancer Center

Rochester, Minnesota, 55905, United States

Location

CCOP - Metro-Minnesota

Saint Louis Park, Minnesota, 55416, United States

Location

Park Nicollet Cancer Center

Saint Louis Park, Minnesota, 55416, United States

Location

Regions Hospital Cancer Care Center

Saint Paul, Minnesota, 55101, United States

Location

United Hospital

Saint Paul, Minnesota, 55102, United States

Location

St. Francis Cancer Center at St. Francis Medical Center

Shakopee, Minnesota, 55379, United States

Location

Lakeview Hospital

Stillwater, Minnesota, 55082, United States

Location

Ridgeview Medical Center

Waconia, Minnesota, 55387, United States

Location

Willmar Cancer Center at Rice Memorial Hospital

Willmar, Minnesota, 56201, United States

Location

Minnesota Oncology - Woodbury

Woodbury, Minnesota, 55125, United States

Location

Cancer Resource Center - Lincoln

Lincoln, Nebraska, 68510, United States

Location

CCOP - Missouri Valley Cancer Consortium

Omaha, Nebraska, 68106, United States

Location

Immanuel Medical Center

Omaha, Nebraska, 68122, United States

Location

Alegant Health Cancer Center at Bergan Mercy Medical Center

Omaha, Nebraska, 68124, United States

Location

Lakeside Hospital

Omaha, Nebraska, 68130, United States

Location

Creighton University Medical Center

Omaha, Nebraska, 68131-2197, United States

Location

MeritCare Broadway

Fargo, North Dakota, 58102, United States

Location

Sanford Clinic North-Fargo

Fargo, North Dakota, 58102, United States

Location

CCOP - MeritCare Hospital

Fargo, North Dakota, 58122, United States

Location

Roger Maris Cancer Center at MeritCare Hospital

Fargo, North Dakota, 58122, United States

Location

Sanford Medical Center-Fargo

Fargo, North Dakota, 58122, United States

Location

Altru Cancer Center at Altru Hospital

Grand Forks, North Dakota, 58201, United States

Location

Wood County Oncology Center

Bowling Green, Ohio, 43402, United States

Location

Community Cancer Center

Elyria, Ohio, 44035, United States

Location

Hematology Oncology Center

Elyria, Ohio, 44035, United States

Location

Lima Memorial Hospital

Lima, Ohio, 45804, United States

Location

Northwest Ohio Oncology Center

Maumee, Ohio, 43537-1839, United States

Location

St. Charles Mercy Hospital

Oregon, Ohio, 43616, United States

Location

Toledo Clinic - Oregon

Oregon, Ohio, 43616, United States

Location

Flower Hospital Cancer Center

Sylvania, Ohio, 43560, United States

Location

Mercy Hospital of Tiffin

Tiffin, Ohio, 44883, United States

Location

Toledo Hospital

Toledo, Ohio, 43606, United States

Location

St. Vincent Mercy Medical Center

Toledo, Ohio, 43608, United States

Location

Medical University of Ohio Cancer Center

Toledo, Ohio, 43614, United States

Location

CCOP - Toledo Community Hospital

Toledo, Ohio, 43617, United States

Location

St. Anne Mercy Hospital

Toledo, Ohio, 43623, United States

Location

Toledo Clinic, Incorporated - Main Clinic

Toledo, Ohio, 43623, United States

Location

Fulton County Health Center

Wauseon, Ohio, 43567, United States

Location

Fredericksburg Oncology, Incorporated

Fredericksburg, Virginia, 22401, United States

Location

Marshfield Clinic - Chippewa Center

Chippewa Falls, Wisconsin, 54729, United States

Location

Center for Cancer Treatment & Prevention at Sacred Heart Hospital

Eau Claire, Wisconsin, 54701, United States

Location

Marshfield Clinic Cancer Care at Regional Cancer Center

Eau Claire, Wisconsin, 54701, United States

Location

Marshfield Clinic - Ladysmith Center

Ladysmith, Wisconsin, 54848, United States

Location

Marshfield Clinic - Marshfield Center

Marshfield, Wisconsin, 54449, United States

Location

Saint Joseph's Hospital

Marshfield, Wisconsin, 54449, United States

Location

Marshfield Clinic - Lakeland Center

Minocqua, Wisconsin, 54548, United States

Location

Ministry Medical Group at Saint Mary's Hospital

Rhinelander, Wisconsin, 54501, United States

Location

Marshfield Clinic - Indianhead Center

Rice Lake, Wisconsin, 54868, United States

Location

Marshfield Clinic at Saint Michael's Hospital

Stevens Point, Wisconsin, 54481, United States

Location

Saint Michael's Hospital Cancer Center

Stevens Point, Wisconsin, 54481, United States

Location

Marshfield Clinic - Wausau Center

Wausau, Wisconsin, 54401, United States

Location

Diagnostic and Treatment Center

Weston, Wisconsin, 54476, United States

Location

Marshfield Clinic - Weston Center

Weston, Wisconsin, 54476, United States

Location

Ministry Saint Clare's Hospital

Weston, Wisconsin, 54476, United States

Location

Marshfield Clinic - Wisconsin Rapids Center

Wisconsin Rapids, Wisconsin, 54494, United States

Location

Related Publications (1)

  • 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.

MeSH Terms

Conditions

Head and Neck NeoplasmsMucositisPainSquamous Cell Carcinoma of Head and NeckEsthesioneuroblastoma, OlfactorySalivary Gland NeoplasmsTongue Neoplasms

Interventions

Doxepin

Condition Hierarchy (Ancestors)

Neoplasms by SiteNeoplasmsGastroenteritisGastrointestinal DiseasesDigestive System DiseasesMouth DiseasesStomatognathic DiseasesNeurologic ManifestationsSigns and SymptomsPathological Conditions, Signs and SymptomsCarcinoma, Squamous CellCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeuroblastomaNeuroectodermal Tumors, Primitive, PeripheralNeuroectodermal Tumors, PrimitiveNeoplasms, NeuroepithelialNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms, Nerve TissueOlfactory Nerve DiseasesCranial Nerve DiseasesNervous System DiseasesMouth NeoplasmsSalivary Gland DiseasesTongue Diseases

Intervention Hierarchy (Ancestors)

OxepinsEthers, CyclicEthersOrganic ChemicalsDibenzoxepinsHeterocyclic Compounds, 3-RingHeterocyclic Compounds, Fused-RingHeterocyclic Compounds

Results Point of Contact

Title
Robert C. Miller, M.D.
Organization
Mayo Clinic

Study Officials

  • Robert C. Miller, MD

    Mayo Clinic

    STUDY CHAIR

Publication Agreements

PI is Sponsor Employee
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
SUPPORTIVE CARE
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 1, 2010

First Posted

July 2, 2010

Study Start

December 1, 2010

Primary Completion

May 1, 2012

Study Completion

March 2, 2015

Last Updated

August 9, 2017

Results First Posted

May 8, 2017

Record last verified: 2017-07

Locations