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
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- Mayo Clinic
- 入组人数
- 5
- 试验地点
- 3
- 主要终点
- Change in Mouth Pain as Measured by Average Area Under the Curve Per Assessment
研究概览
简要总结
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.
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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)
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Doxepin Hydrochloride (Drug)
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.
干预措施: Quality-of-Life Assessment (Other)
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.
干预措施: Questionnaire Administration (Other)
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.
干预措施: Placebo (Other)
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.
干预措施: Quality-of-Life Assessment (Other)
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.
干预措施: Questionnaire Administration (Other)
结局指标
主要结局
Change in Mouth Pain as Measured by Average Area Under the Curve Per Assessment
时间窗: Baseline and 5, 15, 30, 60, 120, and 240 minutes after treatment on day 1
Average Area Under the Curve per assessment (aAUCpa) of pain for the first cycle of treatment. Scores are reported on a 0-100 scale, where 100=better outcome QOL. The aAUCpa is the average of each AUC between each sequential assessment. Patients will assess their pain at baseline and at 5, 15, 30, 60, 120, and 240 minutes after treatment. The AUC calculation is based on the assessment number (1,2,3,4,5,6) instead of the actual number of minutes (5,15,30,60,120,240). This results in an AUC measure that is the average pain score across all of the measurements and is not a function of the number of minutes from treatment. The area under the curve of these 6 time points will be adjusted by their baseline pain score. The pain scores at each time point are given equal weights in the AUC calculation and the AUC calculation does not use the number of minutes after treatment. Therefore, the AUC measurement scale is the same as the original pain score scale.
次要结局
- Incidence of Any Grade 3 or Higher Adverse Events Using Common Terminology Criteria for Adverse Events (CTCAE)(Up to 4 hours after treatment)
- Use of Alternative Analgesics(Up to 4 hours after treatment)
- Patient Preference for Continued Therapy at Initial Dose and Crossover(At initial Day 1 dose and Day 3 crossover dose.)