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
Trial status: Open for Enrollment
Why is this study being done?
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.
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.
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.
Who is eligible to participate?
- 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
- 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