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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Mayo Clinic
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT02062632
First received: February 12, 2014
Last updated: September 12, 2014
Last verified: September 2014
  Purpose

This pilot randomized clinical trial studies the effects, good and/or bad, of taking doxepin hydrochloride compared to placebo (inactive drug) in treating esophageal pain in patients with thoracic cancer 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. Part of doxepin hydrochloride's drug action takes place at the surface of the esophagus, which may be helpful in reducing the pain caused by radiation therapy.


Condition Intervention
Lymphoma
Malignant Mesothelioma
Malignant Pericardial Effusion
Malignant Pleural Effusion
Non-small Cell Lung Cancer
Small Cell Lung Cancer
Soft Tissue Sarcoma
Thymoma and Thymic Carcinoma
Drug: doxepin hydrochloride
Other: placebo
Procedure: quality-of-life assessment
Other: questionnaire administration
Other: laboratory procedure

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: MC13C1, 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:
  • 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

  • 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.

  • 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 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 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

  • 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.

  • 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.

  • 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.


Other Outcome Measures:
  • Individual genetic variaiants [ Time Frame: At baseline ] [ Designated as safety issue: No ]
    Comparative statistics will be used to explore the relationship between individual genetic variants (TGFB1, tPA, and ACE) and radiation-induced thoracic injuries (RITT). These analyses will include scatterplots, spearman correlations, t-tests and chi-square tests.

  • 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 RITT. These analyses will include scatterplots, spearman correlations, t-tests and chi-square tests.

  • 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.

  • 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.


Estimated Enrollment: 50
Study Start Date: March 2014
Estimated Primary Completion Date: October 2015 (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
  • doxepin
  • Sinequan
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Other: questionnaire administration
Correlative studies
Other: laboratory procedure
Correlative studies
Other Names:
  • Laboratory Test
  • Test
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 Name: PLCB
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Other: questionnaire administration
Correlative studies
Other: laboratory procedure
Correlative studies
Other Names:
  • Laboratory Test
  • Test

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.

II. To explore the relationship of individual genetic variants of transforming growth factor beta 1 (TGFB1), tissue plasminogen activator (tPA), and angiotensin I converting enzyme (ACE) to baseline quality-of-life (European Organization for Research and Treatment of Cancer [EORTC] and Functional Assessment of Cancer Treatment-Lung [FACT-L]) and treatment outcomes such as radiation-induced thoracic injuries (RITT) including esophagitis.

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
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), lymphoma, thymoma, thymic carcinoma, mesothelioma, sarcoma, and pulmonary or pleural-based metastases
  • Planned RT (with or without chemotherapy) to a dose of >= 20 Gray (Gy) using 1.60 to 4.00 Gy per daily fraction; if radiation is given twice daily, a cumulative planned dose of >= 15 Gy using 1.25 to 2.75 Gy per fraction is required
  • At least 5 cm of the esophagus must be planned to receive radiotherapy, with a minimum dose of at least 10 Gy
  • >= 4 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
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2
  • Direct bilirubin < 2.0 x upper limit of normal (ULN)
  • Aspartate transaminase (AST) =< 4 x ULN
  • 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)
  • Willing to provide blood samples for correlative research purposes

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
  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 Recruiting
Rochester, Minnesota, United States, 55905
Contact: Clinical Trials Referral Office    855-776-0015      
Principal Investigator: Robert C. Miller         
United States, Nebraska
University of Nebraska Medical Center Not yet recruiting
Omaha, Nebraska, United States, 68198
Contact: Apar K. Ganti    402-559-6520    aganti@unmc.edu   
Principal Investigator: Apar K. Ganti         
Sponsors and Collaborators
Mayo Clinic
Investigators
Principal Investigator: Robert Miller Mayo Clinic
  More Information

No publications provided

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: September 12, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Pericardial Effusion
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Small Cell Lung Carcinoma
Sarcoma
Mesothelioma
Neoplasms, Mesothelial
Pleural Effusion
Pleural Effusion, Malignant
Thymoma
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Adenoma
Neoplasms, Glandular and Epithelial
Pleural Diseases
Pleural Neoplasms
Heart Diseases
Cardiovascular Diseases
Neoplasms, Complex and Mixed
Thymus Neoplasms
Lymphatic Diseases
Doxepin

ClinicalTrials.gov processed this record on October 01, 2014