Clinical trial NCT02062632: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: 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
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2014-02-14
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.

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

Primary outcomes:
measure: Change in Mouth Pain as Measured by Average Area Under the Curve Per Assessment
timeFrame: Baseline and 5, 15, 30, 60, 120, and 240 minutes after treatment on day 1
Secondary outcomes:
measure: Incidence of Any Grade 3 or Higher Adverse Events Using Common Terminology Criteria for Adverse Events (CTCAE)
timeFrame: Up to 4 hours after treatment
measure: Use of Alternative Analgesics
timeFrame: Up to 4 hours after treatment
measure: Patient Preference for Continued Therapy at Initial Dose and Crossover
timeFrame: At initial Day 1 dose and Day 3 crossover dose.
Other outcomes:
measure: Incidence of Adverse Events Graded According to Common Terminology Criteria for Adverse Events, Radiation Therapy Oncology Group, and Patient Reported Outcomes (Continuation Phase)
timeFrame: Up to 3 months
measure: Pain Levels (Continuation Phase)
timeFrame: Up to 3 months
measure: 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
timeFrame: Up to 4 hours after treatment
Locations:
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Green Bay
country: United States
facility: Green Bay Oncology Limited at Saint Mary's Hospital
state: Wisconsin
Study officials:
affiliation: Mayo Clinic
name: Terence Sio
role: PRINCIPAL_INVESTIGATOR
References: