Esophageal CarcinomaPhase 2NCT02062632
Doxepin Hydrochloride in Treating Esophageal Pain in Patients With Thoracic Cancer Receiving Radiation Therapy to the Thorax With or Without Chemotherapy
A Phase 2 study testing Doxepin Hydrochloride, Quality-of-Life Assessment and Questionnaire Administration in people with Esophageal Carcinoma and Hypopharyngeal Carcinoma, run by Mayo Clinic at 3 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Esophageal Carcinoma, Hypopharyngeal Carcinoma, Laryngeal Carcinoma
- What is being tested?
- Doxepin Hydrochloride, Quality-of-Life Assessment and Questionnaire Administration
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 5 participants
- Where
- 3 sitesUnited States
- Study dates
- 14 Apr 2014to 6 Nov 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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)
Who cannot join
- 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
Show all 12Show fewer
- 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
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Green Bay Oncology Limited at Saint Mary's Hospital
Green Bay, Wisconsin, 54303
University of Nebraska Medical Center
Omaha, Nebraska, 68198
Mayo Clinic
Rochester, Minnesota, 55905
About this study
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
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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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:
- 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.
- Conditions
- Esophageal Carcinoma, Hypopharyngeal Carcinoma, Laryngeal Carcinoma, Lymphoma, Mesothelioma, Metastatic Malignant Neoplasm in the Lung
- Being tested
- Doxepin Hydrochloride, Placebo, Quality-of-Life Assessment, Questionnaire Administration
- Medical subject headings
- Esophageal Neoplasms, Hypopharyngeal Neoplasms, Laryngeal Neoplasms, Lymphoma, Mesothelioma, Carcinoma, Non-Small-Cell Lung, Sarcoma, Small Cell Lung Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Doxepin HydrochlorideDrug
Also called Adapin, Sinequan
Given orally
PlaceboOther
Also called placebo therapy, PLCB, sham therapy
Given orally
Quality-of-Life AssessmentOther
Also called Quality of Life Assessment
Ancillary studies
Questionnaire AdministrationOther
Ancillary studies
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Other: Placebo; Other: Quality-of-Life Assessment; Other: Questionnaire Administration |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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)
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
Measured: Up to 4 hours after treatment
Use of Alternative Analgesics
Subgroup analyses will be performed to determine differential effects within the two stratification factors.
Measured: Up to 4 hours after treatment
Patient Preference for Continued Therapy at Initial Dose and Crossover
Measured: At initial Day 1 dose and Day 3 crossover dose.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Feb 2014 (estimated)
- Study start14 Apr 2014
- Primary completion29 May 2015
- Study completion6 Nov 2017
Why it stopped: Poor accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Esophageal CarcinomaStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Terence Sio, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02062632
- Sponsor's protocol ID
- MC13C1
- Other IDs
- NCI-2014-00253, MC13C1, P30CA015083
- Status last verified
- Nov 2018
- First submitted
- 12 Feb 2014
- Last updated
- 1 Oct 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 1 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02062632
- Acronym / sponsor ID
- MC13C1
- Conditions
- Esophageal Carcinoma, Hypopharyngeal Carcinoma, Laryngeal Carcinoma, Lymphoma, Mesothelioma, Metastatic Malignant Neoplasm in the Lung
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Poor accrual
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 14 Apr 2014 (actual)
- Primary completion
- 29 May 2015 (actual)
- Study completion
- 6 Nov 2017 (actual)
- First posted
- 14 Feb 2014 (estimated)
- Results
- Posted 1 Oct 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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:
- 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:
- 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.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group I (doxepin hydrochloride) | Experimental | Drug: Doxepin Hydrochloride, Other: Quality-of-Life Assessment, Other: Questionnaire AdministrationPatients 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 (placebo) | Placebo comparator | Other: Placebo, Other: Quality-of-Life Assessment, Other: Questionnaire AdministrationPatients receive placebo oral solution (swish, gargle for 30 seconds, and slowly swallow) on day 1. Patients then crossover to Arm I on day 3. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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
- Able to swallow the study medication
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Doxepin HydrochlorideAlso: Adapin, SinequanGiven orally | Drug | Group I (doxepin hydrochloride) |
| PlaceboAlso: placebo therapy, PLCB, sham therapyGiven orally | Other | Group II (placebo) |
| Quality-of-Life AssessmentAlso: Quality of Life AssessmentAncillary studies | Other | Group I (doxepin hydrochloride), Group II (placebo) |
| Questionnaire AdministrationAncillary studies | Other | Group I (doxepin hydrochloride), Group II (placebo) |
Primary outcome
Change in Mouth Pain as Measured by Average Area Under the Curve Per Assessment
Time frame: Baseline and 5, 15, 30, 60, 120, and 240 minutes after treatment on day 1
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.
3 secondary outcomes
Incidence of Any Grade 3 or Higher Adverse Events Using Common Terminology Criteria for Adverse Events (CTCAE)
Time frame: Up to 4 hours after treatment
Use of Alternative Analgesics
Time frame: Up to 4 hours after treatment
Patient Preference for Continued Therapy at Initial Dose and Crossover
Time frame: At initial Day 1 dose and Day 3 crossover dose.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Oct 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Terence Sio principal investigator
Mayo Clinic
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Doxepin Hydrochloride, Quality-of-Life Assessment and Questionnaire Administration in people with Esophageal Carcinoma and Hypopharyngeal Carcinoma, run by Mayo Clinic at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 1 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Oct 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Mouth Pain as Measured by Average Area Under the Curve Per Assessment (time frame: Baseline and 5, 15, 30, 60, 120, and 240 minutes after treatment on day 1). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Oct 2019.