Brief Title
Doxepin Hydrochloride in Treating Esophageal Pain in Patients With Thoracic Cancer Receiving Radiation Therapy to the Thorax With or Without Chemotherapy
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
Brief Summary
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.
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.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
Change in Mouth Pain as Measured by Average Area Under the Curve Per Assessment
Secondary Outcome
Incidence of Any Grade 3 or Higher Adverse Events Using Common Terminology Criteria for Adverse Events (CTCAE)
Condition
Esophageal Carcinoma
Intervention
Doxepin Hydrochloride
Study Arms / Comparison Groups
Group I (doxepin hydrochloride)
Description: 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.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
5
Start Date
April 14, 2014
Completion Date
November 6, 2017
Primary Completion Date
May 29, 2015
Eligibility 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
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Terence Sio, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT02062632
Organization ID
MC13C1
Secondary IDs
NCI-2014-00253
Responsible Party
Sponsor
Study Sponsor
Mayo Clinic
Collaborators
National Cancer Institute (NCI)
Study Sponsor
Terence Sio, Principal Investigator, Mayo Clinic
Verification Date
November 2018