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Thyroid Diseases

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Pharmaceutical Solutions

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Central Nervous System Depressants

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Doxepin

Diphenhydramine

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Histamine Antagonists

Histamine

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Neurotransmitter Agents

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.

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.

Doxepin Hydrochloride

Placebo

Quality-of-Life Assessment

Questionnaire Administration

Terence Sio

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.

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.

Doxepin Hydrochloride in Treating Esophageal Pain in Patients With Thoracic Cancer Receiving Radiation Therapy to the Thorax With or Without Chemotherapy

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

Means and proportions, along with 95% confidence intervals and plots over time will be reported for adverse event levels by week.

Means and proportions, along with 95% confidence intervals and plots over time will be reported for pain levels by week.

Comparative statistics will be used to explore the relationship between quality of life and radiation-induced thoracic toxicities. These analyses will include scatterplots, spearman correlations, t-tests and chi-square tests.

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.

Incidence of any grade 3 or higher adverse events using Common Terminology Criteria for Adverse Events (CTCAE). Number or patients reporting a grade 3 or higher adverse event according to CTCAE

Subgroup analyses will be performed to determine differential effects within the two stratification factors.

National Cancer Institute (NCI)

Mayo Clinic

Since only one patient was accrued and completed the study on one arm, patient confidentiality prevents the reporting of results per intervention. Therefore, the study results are only reported for the first study period (before crossover) and only for a single intervention (placebo).Serious AE (SAE) reports may include any serious or non-serious events considered related to the primary event; collectively, these events are referred to as Expedited AEs, \& appear in the SAE table.

Patients receive placebo oral solution (swish, gargle for 30 seconds, and slowly swallow) on day 1.

Age, Continuous

Sex: Female, Male

5 were accrued but only 3 provided data. Since only 1 patient was accrued \& completed the study on 1 arm, patient confidentiality prevents the reporting of results per intervention. 2nd crossover was optional; none chose to crossover. The study results are only reported for the 1st study period (before crossover) \& only for placebo intervention.

Terence T. Sio, MD, MS

Patient #1

Patient #2

Patient #3

Change in Mouth Pain as Measured by Average Area Under the Curve Per Assessment

Incidence of Any Grade 3 or Higher Adverse Events Using Common Terminology Criteria for Adverse Events (CTCAE)

Only patients who submitted data on alternative analgesics are evaluable for this outcome measure. None of the patients provided information about alternative analgesics, so this secondary outcome could not be analyzed.

Use of Alternative Analgesics

Only patients who submitted data on patient preference are evaluable for this outcome measure. Since none of the patients crossed over to the optional phase of the study, this secondary outcome could not be analyzed.

Patient Preference for Continued Therapy at Initial Dose and Crossover

Incidence of Adverse Events Graded According to Common Terminology Criteria for Adverse Events, Radiation Therapy Oncology Group, and Patient Reported Outcomes (Continuation Phase)

Pain Levels (Continuation Phase)

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

Overall Study

Spots Global Cancer Trial Database for metastatic malignant neoplasm in the pleura