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Doxepin Hydrochloride in Treating Esophageal Pain in Patients With Thoracic Cancer Receiving Radiation Therapy to the Thorax With or Without Chemotherapy

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02062632
First Posted: February 14, 2014
Last Update Posted: December 4, 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):
Mayo Clinic
  Purpose
This randomized pilot clinical trial studies the effects of taking doxepin hydrochloride as compared to placebo (inactive drug) in treating esophageal pain in patients with cancer located in the chest area receiving radiation therapy to the thorax with or without chemotherapy. Doxepin hydrochloride is a tricyclic antidepressant drug which was recently shown to be helpful for mouth pain in patients receiving radiation therapy. Doxepin hydrochloride affects the surface of the esophagus, which may be helpful in reducing the pain caused by radiation therapy.

Condition Intervention
Esophageal Carcinoma Hypopharyngeal Carcinoma Laryngeal Carcinoma Lymphoma Mesothelioma Metastatic Malignant Neoplasm in the Lung Metastatic Malignant Neoplasm in the Pleura Metastatic Malignant Neoplasm in the Spinal Cord Non-Small Cell Lung Carcinoma Sarcoma Small Cell Lung Carcinoma Thymic Carcinoma Thymoma Thyroid Gland Carcinoma Drug: Doxepin Hydrochloride Other: Placebo Other: Quality-of-Life Assessment Other: Questionnaire Administration

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Supportive Care
Official Title: A Pilot, Double-Blind, Randomized, Two-Arm Crossover Study of Doxepin Versus Placebo for Esophagitis-Induced Pain in Patients Receiving Radiotherapy to the Thorax With or Without Chemotherapy

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Change in mouth pain using a 0 to 10 numerical analogue scale [ Time Frame: Baseline and 5, 15, 30, 60, 120, and 240 minutes after treatment on day 1 ]
    Patients will assess their pain at baseline and at 5, 15, 30, 60, 120, and 240 minutes after treatment. The area under the curve of these 6 time points will be adjusted by their baseline pain score and compared between groups. The primary endpoint will be based on the area under the curve values only in the first period before the crossover. This difference between groups will be tested using a one-sided t-test with a 10% type I error rate.


Secondary Outcome Measures:
  • Incidence of any grade 3 or higher adverse events using Common Terminology Criteria for Adverse Events (CTCAE) [ Time Frame: Up to 4 hours after treatment on day 3 ]
    Number or patients reporting a grade 3 or higher adverse event according to CTCAE

  • Incidence of any grade 3 or higher adverse event rates using Radiation Therapy Oncology Group [ Time Frame: Up to 4 hours after treatment on day 3 ]
    Standard crossover analyses will be used for continuous endpoints.

  • Adverse event rates using Patient Reported Outcomes (PROs) on Day 1 and Day 3 crossover [ Time Frame: Baseline and 5, 15, 30, 60, 120, and 240 minutes after treatment on day 1 and day 3 ]
    The patient reported outcomes will include stinging or burning, taste change, drowsiness, and allergic reactions (if any). Differences in PROs will be tested in the first period using two-sample, one-sided t-tests with 10% error rates.

  • Maximum graded adverse events using Common Terminology Criteria for Adverse Events (CTCAE) [ Time Frame: Up to 4 hours after treatment on day 3 ]
    The patient reported outcomes will include stinging or burning, taste change, drowsiness, and allergic reactions (if any).

  • Use of alternative analgesics [ Time Frame: Up to 4 hours after treatment ]
    Subgroup analyses will be performed to determine differential effects within the two stratification factors.

  • Patient preference for continued therapy at initial dose and crossover [ Time Frame: At initial Day 1 dose and Day 3 crossover dose. ]

Other Outcome Measures:
  • Incidence of adverse events graded according to Common Terminology Criteria for Adverse Events, Radiation Therapy Oncology Group, and patient reported outcomes (continuation phase) [ Time Frame: Up to 3 months ]
    Means and proportions, along with 95% confidence intervals and plots over time will be reported for adverse event levels by week.

  • Pain levels (continuation phase) [ Time Frame: Up to 3 months ]
    Means and proportions, along with 95% confidence intervals and plots over time will be reported for pain levels by week.

  • Quality of life using European Organization for Research and Treatment of Cancer Quality of Life-Lung Cancer 13 and Functional Assessment of Cancer Therapy-Lung [ Time Frame: Up to 4 hours after treatment ]
    Comparative statistics will be used to explore the relationship between quality of life and radiation-induced thoracic toxicities. These analyses will include scatterplots, spearman correlations, t-tests and chi-square tests.


Estimated Enrollment: 50
Actual Study Start Date: April 14, 2014
Estimated Study Completion Date: October 14, 2018
Estimated Primary Completion Date: October 14, 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group I (doxepin hydrochloride)
Patients receive doxepin hydrochloride oral solution (swish, gargle for 30 seconds, and slowly swallow) on day 1. Patients then crossover to Arm II on day 3.
Drug: Doxepin Hydrochloride
Given orally
Other Names:
  • Adapin
  • Sinequan
Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment
Other: Questionnaire Administration
Ancillary studies
Placebo Comparator: Group II (placebo)
Patients receive placebo oral solution (swish, gargle for 30 seconds, and slowly swallow) on day 1. Patients then crossover to Arm I on day 3.
Other: Placebo
Given orally
Other Names:
  • placebo therapy
  • PLCB
  • sham therapy
Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment
Other: Questionnaire Administration
Ancillary studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To provide baseline data regarding the effectiveness of doxepin (doxepin hydrochloride) in reducing esophagitis-related pain in patients undergoing radiation therapy (RT) to the thorax, as measured by a patient-reported questionnaire at 5 minutes, 15 minutes, 30 minutes, 1 hour and then at 2 and 4 hours on day 1.

SECONDARY OBJECTIVES:

I. To assess the adverse event profile of doxepin swish and swallow using a patient-reported questionnaire at 5 minutes, 15 minutes, 30 minutes, 1 hour and then at 2 and 4 hours using Common Terminology Criteria for Adverse Events (CTCAE) and Radiation Therapy Oncology Group (RTOG) acute toxicity criteria, and also for domains of unpleasant taste, burning/stinging discomfort, and drowsiness.

II. To evaluate the effectiveness of doxepin in reducing esophagitis-related pain in patients undergoing RT to the thorax, as measured by a patient-reported questionnaire at 5 minutes, 15 minutes, 30 minutes, 1 hours and then at 2 and 4 hours on days 1 and 3 (including the cross-over phase).

III. To compare and provide baseline data regarding alternative analgesic use between the doxepin and placebo arms.

IV. To provide baseline data regarding the patients? preference for continued therapy with doxepin or placebo after initial test dose or after the cross-over phase, as measured by items 9 and 10 in the patient-reported questionnaire at 4 hours after administration of the study medication and the actual participation rate.

TERTIARY OBJECTIVES:

I. To assess pain reduction and other adverse event profile in the optional continuation phase of doxepin oral rinse therapy. (Only applies to patients who have the optional continuation of doxepin oral rinse after the first two phases)

OUTLINE: Patients are randomized to 1 of 2 treatment groups.

GROUP I: Patients receive doxepin hydrochloride oral solution (swish, gargle for 30 seconds, and slowly swallow) on day 1. Patients then crossover to Arm II on day 3.

GROUP II: Patients receive placebo oral solution (swish, gargle for 30 seconds, and slowly swallow) on day 1. Patients then crossover to Arm I on day 3.

In both arms, patients may continue to receive doxepin hydrochloride oral solution every 4 hours as needed during radiation therapy.

  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:

  • Histological confirmation of thoracic malignancies including non-small cell lung cancer (NSCLC), small lung cancer (SCLC), esophageal cancer, hypopharyngeal and laryngeal cancers (for which esophagitis symptoms can be relieved by doxepin swallow), lymphoma, thyroid, thymoma, thymic carcinoma, mesothelioma, sarcoma, and spinal, pulmonary or pleural-based metastases
  • Planned RT (with or without chemotherapy) to a dose of >= 20 Gray (Gy) using 1.60 Gy per daily fraction; if radiation is given twice daily, a cumulative planned dose of >= 15 Gy using at least 1.25 Gy per fraction is required; hypofractionated and stereotactic body radiation therapy regimen are allowed
  • At least 5 cm of the esophagus must be planned to receive radiotherapy, with a minimum dose of at least 10 Gy
  • >= 3 esophageal pain, either at rest or during swallowing, felt to be related to esophagitis for which the patient wants relief, as measured by asking the following question

    • ?On a scale of 0 to 10 (0 = no pain; 10 = worst pain), what number best describes your chest pain* (right now) due to your radiation treatment??

      • Radiation can cause inflammation in your esophagus which can feel like a chest pain, either at rest or during swallowing
  • Able to swallow the study medication
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2
  • Negative pregnancy test done =< 28 days prior to registration, for women of childbearing potential only
  • Ability to complete questionnaire(s) by themselves or with assistance
  • Provide informed written consent
  • Willingness to complete evaluation and questionnaires per protocol at the participating institution for follow-up (during the active monitoring phase of the study)

Exclusion Criteria:

  • Known allergy to doxepin, tricyclic antidepressants, or any known component of the drug formulation
  • Histologic proof of and getting treatment for esophageal, stomach, spinal cord, thyroid, breast, and head and neck cancers and vertebral metastases
  • Use of a tricyclic antidepressant or monoamine oxidase inhibitor within the 2 weeks prior to registration
  • The presence or strong clinical suspicion of a tracheoesophageal fistula, or known esophageal invasion by cancer
  • Current untreated or unresolved esophageal candidiasis or herpes simplex virus (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

    • Pregnant women
    • Nursing women
  • Current use of doxepin or doxepin rinse as a swallow preparation
  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): NCT02062632


Locations
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, Nebraska
University of Nebraska Medical Center
Omaha, Nebraska, United States, 68198
United States, Wisconsin
Green Bay Oncology Limited at Saint Mary's Hospital
Green Bay, Wisconsin, United States, 54303
Sponsors and Collaborators
Mayo Clinic
National Cancer Institute (NCI)
Investigators
Principal Investigator: Terence Sio Mayo Clinic
  More Information

Responsible Party: Mayo Clinic
ClinicalTrials.gov Identifier: NCT02062632     History of Changes
Other Study ID Numbers: MC13C1
NCI-2014-00253 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
MC13C1 ( Other Identifier: Mayo Clinic )
P30CA015083 ( U.S. NIH Grant/Contract )
First Submitted: February 12, 2014
First Posted: February 14, 2014
Last Update Posted: December 4, 2017
Last Verified: February 2017

Additional relevant MeSH terms:
Carcinoma
Neoplasms
Mesothelioma
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Thymoma
Esophageal Neoplasms
Small Cell Lung Carcinoma
Neoplasms, Second Primary
Thyroid Neoplasms
Pleural Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Adenoma
Neoplasms, Mesothelial
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Neoplasms, Complex and Mixed
Thymus Neoplasms
Lymphatic Diseases
Gastrointestinal Neoplasms
Digestive System Neoplasms
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases