We updated the design of this site on September 25th. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01156142
First Posted: July 2, 2010
Last Update Posted: August 9, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology
  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 (Participant, 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:


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 ]
    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:
  • Total Taste of the Oral Rinse [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.


Enrollment: 155
Study Start Date: December 2010
Study Completion Date: March 2, 2015
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

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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 ( Registry Identifier: CTRP (Clinical Trials Reporting System) )
CDR0000675520 ( Registry Identifier: PDQ (Physician Data Query) )
U10CA037404 ( U.S. NIH Grant/Contract )
First Submitted: July 1, 2010
First Posted: July 2, 2010
Results First Submitted: December 12, 2016
Results First Posted: May 8, 2017
Last Update Posted: August 9, 2017
Last Verified: July 2017

Keywords provided by Alliance for Clinical Trials in Oncology:
salivary gland acinic cell tumor
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

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