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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT02062632
First received: February 12, 2014
Last updated: August 16, 2016
Last verified: April 2016
  Purpose
This pilot randomized 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.

Condition Intervention
Esophageal Carcinoma
Hypopharyngeal Carcinoma
Laryngeal Carcinoma
Lymphoma
Malignant Mesothelioma
Malignant Pleural Effusion
Metastatic Malignant Neoplasm in the Spinal Cord
Non-Small Cell Lung Carcinoma
Sarcoma
Small Cell Lung Carcinoma
Thymic Carcinoma
Thymoma
Thyroid Gland Carcinoma
Drug: Doxepin Hydrochloride
Other: Placebo
Other: Quality-of-Life Assessment
Other: Questionnaire Administration

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Supportive Care
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

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Change in mouth pain using a 0 to 10 numerical analogue scale for mouth pain [ Time Frame: Baseline to up to 4 hours after treatment on day 1 ] [ Designated as safety issue: No ]
    Patients will assess their pain at baseline and at 5, 15, 30, 60, 120, and 240 minutes after treatment. The area under the curve (AUC) of these 6 time points will be adjusted by their baseline pain score and compared between groups. The primary endpoint will be based on the AUC values only in the first period before the crossover. This difference between groups will be tested using a one-sided t-test with a 10% type I error rate.


Secondary Outcome Measures:
  • Adverse event rates using CTCAE, RTOG and PRO [ Time Frame: Up to 4 hours after treatment on day 3 ] [ Designated as safety issue: Yes ]
    Standard crossover analyses will be used for continuous endpoints.

  • Change in mouth pain using crossover analysis [ Time Frame: Up to 4 hours after treatment on day 3 ] [ Designated as safety issue: No ]
    Standard crossover analyses will be used for continuous endpoints.

  • Incidence of drowsiness [ Time Frame: Up to 4 hours after treatment ] [ Designated as safety issue: No ]
    Subgroup analyses will be performed to determine differential effects within the two stratification factors.

  • Incidence of grade 3 or higher adverse events as measured by CTCAE and RTOG adverse event grade scales, and patient-reported outcomes (PRO) [ Time Frame: Up to 4 hours after treatment on day 1 ] [ Designated as safety issue: Yes ]
    This endpoint will be compared between arms in the first study period (day one) using a one-sided chi-square test with a 0.10 level of significance. PROs will be measured using 0 to 10 numerical analogue scales. These PROs will include stinging or burning, taste change, drowsiness, and allergic reactions (if any). Differences in PROs will be tested in the first period using two-sample, one-sided t-tests with 10% error rates

  • Incidence of stinging or burning [ Time Frame: Up to 4 hours after treatment ] [ Designated as safety issue: No ]
    Subgroup analyses will be performed to determine differential effects within the two stratification factors.

  • Incidence of unpleasant taste [ Time Frame: Up to 4 hours after treatment ] [ Designated as safety issue: No ]
    Subgroup analyses will be performed to determine differential effects within the two stratification factors

  • Maximum reported CTCAE grade [ Time Frame: Up to 4 hours after treatment ] [ Designated as safety issue: Yes ]
    Subgroup analyses will be performed to determine differential effects within the two stratification factors.

  • Use of alternative analgesics [ Time Frame: Up to 4 hours after treatment ] [ Designated as safety issue: No ]
    Subgroup analyses will be performed to determine differential effects within the two stratification factors.


Other Outcome Measures:
  • Incidence of adverse events graded according to CTCAE, RTOG, and PRO (continuation phase) [ Time Frame: Up to 3 months ] [ Designated as safety issue: Yes ]
    Means and proportions, along with 95% confidence intervals and plots over time will be reported for adverse event levels by week.

  • Pain levels (continuation phase) [ Time Frame: Up to 3 months ] [ Designated as safety issue: No ]
    Means and proportions, along with 95% confidence intervals and plots over time will be reported for pain levels by week.

  • Quality of life using EORTC Quality of Life-Lung Cancer 13 (QOL-LC13) and FACT-L [ Time Frame: Up to 4 hours after treatment ] [ Designated as safety issue: Yes ]
    Comparative statistics will be used to explore the relationship between quality of life and radiation-induced thoracic toxicities (RITT). These analyses will include scatterplots, spearman correlations, t-tests and chi-square tests.


Estimated Enrollment: 50
Study Start Date: April 2014
Estimated Primary Completion Date: October 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: Doxepin Hydrochloride
Given orally
Other Names:
  • Adapin
  • Sinequan
Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment
Other: Questionnaire Administration
Ancillary studies
Placebo Comparator: 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.
Other: Placebo
Given orally
Other Names:
  • placebo therapy
  • PLCB
  • sham therapy
Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment
Other: Questionnaire Administration
Ancillary studies

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

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02062632

Locations
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, Nebraska
University of Nebraska Medical Center
Omaha, Nebraska, United States, 68198
Sponsors and Collaborators
Mayo Clinic
National Cancer Institute (NCI)
Investigators
Principal Investigator: Terence Sio Mayo Clinic
  More Information

Responsible Party: Mayo Clinic
ClinicalTrials.gov Identifier: NCT02062632     History of Changes
Other Study ID Numbers: MC13C1  NCI-2014-00253  MC13C1  P30CA015083 
Study First Received: February 12, 2014
Last Updated: August 16, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma
Mesothelioma
Lung Neoplasms
Pleural Effusion
Neoplasms
Carcinoma, Non-Small-Cell Lung
Thymoma
Esophageal Neoplasms
Small Cell Lung Carcinoma
Pleural Effusion, Malignant
Neoplasms, Second Primary
Thyroid Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Adenoma
Neoplasms, Mesothelial
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Pleural Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Neoplasms, Complex and Mixed
Thymus Neoplasms
Lymphatic Diseases
Gastrointestinal Neoplasms
Digestive System Neoplasms
Head and Neck Neoplasms

ClinicalTrials.gov processed this record on August 25, 2016