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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:
NCT01156142
First received: July 1, 2010
Last updated: August 11, 2016
Last verified: August 2016
History of Changes
  Purpose

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.


Condition Intervention Phase
Head and Neck Cancer
Mucositis
Oral Complications of Radiation Therapy
Pain
 Drug: doxepin hydrochloride
Other: placebo
 Phase 3

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

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Alliance for Clinical Trials in Oncology:

Primary Outcome Measures:
  • Total pain reduction (mouth and throat) [ Time Frame: Baseline and Day 1 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Total taste of the oral rinse [ Time Frame: Up to 9 days ] [ Designated as safety issue: No ]
  • Total stinging or burning from the oral rinse [ Time Frame: Up to 9 days ] [ Designated as safety issue: No ]
  • Total drowsiness increase [ Time Frame: Up to 9 days ] [ Designated as safety issue: No ]
  • Incidence of using alternative analgesics 4 hours before and in between study medications [ Time Frame: Up to 9 days ] [ Designated as safety issue: No ]
  • Patient preference for continuing therapy with oral doxepin hydrochloride [ Time Frame: Up to 9 days ] [ Designated as safety issue: No ]
  • Pain reduction and other adverse event profile in the blinded cross-over phase [ Time Frame: Up to 9 days ] [ Designated as safety issue: Yes ]
  • Long-term outcome of doxepin hydrochloride oral rinse for patient continued therapy [ Time Frame: Up to 9 days ] [ Designated as safety issue: No ]
Enrollment: 162
Study Start Date: December 2010
Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
 Drug: doxepin hydrochloride
Oral rinse
Placebo Comparator: 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.
 Other: placebo
Oral rinse

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.

  Eligibility
Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01156142

  Show 120 Study Locations
Sponsors and Collaborators
Alliance for Clinical Trials in Oncology
National Cancer Institute (NCI)
Investigators
Study Chair: Robert C. Miller, MD Mayo Clinic
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier: NCT01156142     History of Changes
Other Study ID Numbers: NCCTG-N09C6  NCI-2011-02049  CDR0000675520  U10CA037404 
Study First Received: July 1, 2010
Last Updated: August 11, 2016
Health Authority: United States: Food and Drug Administration
United States: NCI Central Institutional Review Board

Keywords provided by Alliance for Clinical Trials in Oncology:
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
metastatic squamous neck cancer with occult primary squamous cell carcinoma
recurrent metastatic squamous neck cancer with occult primary
untreated metastatic squamous neck cancer with occult primary
recurrent lymphoepithelioma of the nasopharynx
recurrent squamous cell carcinoma of the nasopharynx
lymphoepithelioma of the nasopharynx
squamous cell carcinoma of the nasopharynx
recurrent lymphoepithelioma of the oropharynx
recurrent squamous cell carcinoma of the oropharynx
lymphoepithelioma of the oropharynx

Additional relevant MeSH terms:
Head and Neck Neoplasms
Mucositis
Stomatitis
Neoplasms by Site
Neoplasms
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Mouth Diseases
Stomatognathic Diseases
 Doxepin
Antidepressive Agents, Tricyclic
Antidepressive Agents
Psychotropic Drugs
Histamine Antagonists
Histamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 23, 2016