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

NCT02062632 | Terminated Phase 2 Results DMC

• 3 other identifiers: MC13C1NCI-2014-00253P30CA015083
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 3

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline and 5, 15, 30, 60, 120, and 240 minutes after treatment on day 1

Secondary Outcomes (3)

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

  Up to 4 hours after treatment

• Use of Alternative Analgesics

  Up to 4 hours after treatment

• Patient Preference for Continued Therapy at Initial Dose and Crossover

  At initial Day 1 dose and Day 3 crossover dose.

Other Outcomes (3)

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

  Up to 3 months

• Pain Levels (Continuation Phase)

  Up to 3 months

• 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

  Up to 4 hours after treatment

Study Arms (2)

Group I (doxepin hydrochloride)

EXPERIMENTAL

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; Other: Quality-of-Life Assessment; Other: Questionnaire Administration

Group II (placebo)

PLACEBO COMPARATOR

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; Other: Quality-of-Life Assessment; Other: Questionnaire Administration

Interventions

Doxepin Hydrochloride DRUG

Given orally

Also known as: Adapin, Sinequan

Group I (doxepin hydrochloride)

Placebo OTHER

Given orally

Also known as: placebo therapy, PLCB, sham therapy

Group II (placebo)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Group I (doxepin hydrochloride); Group II (placebo)

Questionnaire Administration OTHER

Ancillary studies

Group I (doxepin hydrochloride); Group II (placebo)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Mayo Clinic: lead
• National Cancer Institute (NCI): collaborator

Study Sites (3)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Green Bay Oncology Limited at Saint Mary's Hospital

Green Bay, Wisconsin, 54303, United States

Location

MeSH Terms

Conditions

Esophageal Neoplasms; Hypopharyngeal Neoplasms; Laryngeal Neoplasms; Lymphoma; Mesothelioma; Carcinoma, Non-Small-Cell Lung; Sarcoma; Small Cell Lung Carcinoma; Thymoma; Thyroid Neoplasms

Interventions

Doxepin

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Laryngeal Diseases; Respiratory Tract Diseases; Respiratory Tract Neoplasms; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms, Mesothelial; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Thoracic Neoplasms; Lung Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms, Complex and Mixed; Thymus Neoplasms; Endocrine Gland Neoplasms; Endocrine System Diseases; Thyroid Diseases

Intervention Hierarchy (Ancestors)

Oxepins; Ethers, Cyclic; Ethers; Organic Chemicals; Dibenzoxepins; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Terence T. Sio, MD, MS
• Organization: Mayo Clinic

sio.terence@mayo.edu

507/284-2511

Study Officials

• Terence Sio

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 12, 2014
• First Posted: February 14, 2014
• Study Start: April 14, 2014
• Primary Completion: May 29, 2015
• Study Completion: November 6, 2017
• Last Updated: October 1, 2019
• Results First Posted: October 1, 2019

Record last verified: 2018-11

Locations

US (3)