Doxepin Hydrochloride in Treating Esophageal Pain in Patients With Thoracic Cancer Receiving Radiation Therapy to the Thorax With or Without Chemotherapy
Information source: Mayo Clinic
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Lymphoma; Malignant Mesothelioma; Malignant Pericardial Effusion; Malignant Pleural Effusion; Non-small Cell Lung Cancer; Small Cell Lung Cancer; Soft Tissue Sarcoma; Thymoma and Thymic Carcinoma
Intervention: doxepin hydrochloride (Drug); placebo (Other); quality-of-life assessment (Procedure); questionnaire administration (Other); laboratory procedure (Other)
Phase: N/A
Status: Active, not recruiting
Sponsored by: Mayo Clinic Official(s) and/or principal investigator(s): Robert Miller, Principal Investigator, Affiliation: Mayo Clinic
Summary
This pilot randomized clinical trial studies the effects, good and/or bad, of taking doxepin
hydrochloride compared to placebo (inactive drug) in treating esophageal pain in patients
with thoracic cancer 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. Part of doxepin
hydrochloride's drug action takes place at the surface of the esophagus, which may be
helpful in reducing the pain caused by radiation therapy.
Clinical Details
Official title: MC13C1, 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
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Supportive Care
Primary outcome: Change in mouth pain using a 0 to 10 numerical analogue scale for mouth pain
Secondary outcome: Incidence of grade 3 or higher adverse events as measured by CTCAE and RTOG adverse event grade scales, and patient-reported outcomes (PRO)Maximum reported CTCAE grade Incidence of stinging or burning Incidence of drowsiness Incidence of unpleasant taste Use of alternative analgesics Change in mouth pain using crossover analysis Adverse event rates using CTCAE, RTOG and PRO
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.
II. To explore the relationship of individual genetic variants of transforming growth factor
beta 1 (TGFB1), tissue plasminogen activator (tPA), and angiotensin I converting enzyme
(ACE) to baseline quality-of-life (European Organization for Research and Treatment of
Cancer [EORTC] and Functional Assessment of Cancer Treatment-Lung [FACT-L]) and treatment
outcomes such as radiation-induced thoracic injuries (RITT) including esophagitis.
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
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Histological confirmation of thoracic malignancies including non-small cell lung
cancer (NSCLC), small lung cancer (SCLC), lymphoma, thymoma, thymic carcinoma,
mesothelioma, sarcoma, and pulmonary or pleural-based metastases
- Planned RT (with or without chemotherapy) to a dose of >= 20 Gray (Gy) using 1. 60 to
4. 00 Gy per daily fraction; if radiation is given twice daily, a cumulative planned
dose of >= 15 Gy using 1. 25 to 2. 75 Gy per fraction is required
- At least 5 cm of the esophagus must be planned to receive radiotherapy, with a
minimum dose of at least 10 Gy
- >= 4 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
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2
- Direct bilirubin < 2. 0 x upper limit of normal (ULN)
- Aspartate transaminase (AST) =< 4 x ULN
- 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)
- Willing to provide blood samples for correlative research purposes
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
Locations and Contacts
Mayo Clinic, Rochester, Minnesota 55905, United States
University of Nebraska Medical Center, Omaha, Nebraska 68198, United States
Additional Information
Starting date: March 2014
Last updated: July 29, 2015
|