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

Primary Purpose

Esophageal Carcinoma, Hypopharyngeal Carcinoma, Laryngeal Carcinoma

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Doxepin Hydrochloride
Placebo
Quality-of-Life Assessment
Questionnaire Administration
Sponsored by
Mayo Clinic
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Esophageal Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Mayo Clinic
  • University of Nebraska Medical Center
  • Green Bay Oncology Limited at Saint Mary's Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Group I (doxepin hydrochloride)

Group II (placebo)

Arm Description

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Incidence of Any Grade 3 or Higher Adverse Events Using Common Terminology Criteria for Adverse Events (CTCAE)
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
Use of Alternative Analgesics
Subgroup analyses will be performed to determine differential effects within the two stratification factors.
Patient Preference for Continued Therapy at Initial Dose and Crossover

Full Information

First Posted
February 12, 2014
Last Updated
September 10, 2019
Sponsor
Mayo Clinic
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT02062632
Brief Title
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

2. Study Status

Record Verification Date
November 2018
Overall Recruitment Status
Terminated
Why Stopped
Poor accrual
Study Start Date
April 14, 2014 (Actual)
Primary Completion Date
May 29, 2015 (Actual)
Study Completion Date
November 6, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Mayo Clinic
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
5 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Group I (doxepin hydrochloride)
Arm Type
Experimental
Arm Description
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.
Arm Title
Group II (placebo)
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Doxepin Hydrochloride
Other Intervention Name(s)
Adapin, Sinequan
Intervention Description
Given orally
Intervention Type
Other
Intervention Name(s)
Placebo
Other Intervention Name(s)
placebo therapy, PLCB, sham therapy
Intervention Description
Given orally
Intervention Type
Other
Intervention Name(s)
Quality-of-Life Assessment
Other Intervention Name(s)
Quality of Life Assessment
Intervention Description
Ancillary studies
Intervention Type
Other
Intervention Name(s)
Questionnaire Administration
Intervention Description
Ancillary studies
Primary Outcome Measure Information:
Title
Change in Mouth Pain as Measured by Average Area Under the Curve Per Assessment
Description
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.
Time Frame
Baseline and 5, 15, 30, 60, 120, and 240 minutes after treatment on day 1
Secondary Outcome Measure Information:
Title
Incidence of Any Grade 3 or Higher Adverse Events Using Common Terminology Criteria for Adverse Events (CTCAE)
Description
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
Time Frame
Up to 4 hours after treatment
Title
Use of Alternative Analgesics
Description
Subgroup analyses will be performed to determine differential effects within the two stratification factors.
Time Frame
Up to 4 hours after treatment
Title
Patient Preference for Continued Therapy at Initial Dose and Crossover
Time Frame
At initial Day 1 dose and Day 3 crossover dose.
Other Pre-specified Outcome Measures:
Title
Incidence of Adverse Events Graded According to Common Terminology Criteria for Adverse Events, Radiation Therapy Oncology Group, and Patient Reported Outcomes (Continuation Phase)
Description
Means and proportions, along with 95% confidence intervals and plots over time will be reported for adverse event levels by week.
Time Frame
Up to 3 months
Title
Pain Levels (Continuation Phase)
Description
Means and proportions, along with 95% confidence intervals and plots over time will be reported for pain levels by week.
Time Frame
Up to 3 months
Title
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
Description
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.
Time Frame
Up to 4 hours after treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Terence Sio
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
University of Nebraska Medical Center
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198
Country
United States
Facility Name
Green Bay Oncology Limited at Saint Mary's Hospital
City
Green Bay
State/Province
Wisconsin
ZIP/Postal Code
54303
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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