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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

Published: September 3, 2014

 

Primary Outcome Measure:

  • 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.

Eligibility 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
  • Pregnant or nursing women
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