Fentanyl Pectin Nasal Spray (FNPS) for Exercise-Induced Breakthrough Dyspnea

Study Overview
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Brief Summary
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The goal of this clinical research study is to learn if fentanyl nasal spray can help to control shortness of breath in patients who have been treated or are being treated for cancer. Fentanyl is commonly used for treatment of cancer pain. It may help patients with their shortness of breath as well. In this study, fentanyl will be compared to a placebo. A placebo is not a drug. It looks like the study drug but is not designed to treat any disease or illness. It is designed to be compared with a study drug to learn if the study drug has any real effect.

Detailed Description
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Study Groups: If you are found to be eligible to take part in this study, you will be randomly assigned (as in the flip of a coin) to receive either fentanyl or placebo. You will have an equal chance of being assigned to either group. Neither you nor the study staff will know to which group you have been assigned. However, if needed for your safety, the study staff will be able to find out what you are receiving. Study Drug/Placebo Administration: Before you receive the study drug/placebo, you will walk back and forth in an indoor hallway for up to 6 minutes. You may feel out of breath or become exhausted. You may slow down, stop, and rest at any time you need to. After that, you will sit down and rest (for about 30 minutes). You will then be given the study drug/placebo by a nasal spray. You will then wait for another 20 minutes and repeat the walking test. After that, you will sit down and rest (for about 30 minutes). You will then be given the study drug/placebo again by a nasal spray. You will then wait for another 20 minutes and repeat the walking test for a third time. Study Visit: During your study visit, the study staff will collect information from your medical record about your age, sex, race, disease type, your performance status, any drugs you are taking, and possible causes of shortness of breath. Before each walk test, you will complete the questionnaires about your symptoms. Before and after each walk test, the study staff will record your heart rate, breathing rate, and the level of oxygen in your blood using a measuring device that will be clipped onto your finger. The study staff will also ask you 3 questions about how hard it is to catch your breath and your level of tiredness. During each walk test, you will be asked 6 times how hard it is to catch your breath. The distance you walked and how often and for how long you stopped will be recorded. Before and after the second and third walk tests, the study staff will ask you about any side effects from the study drug/placebo that you may be having. During the rest period between the walk tests, you may be asked several times how hard it is to catch your breath. After each walk test, you will also be asked to complete 4 tests of your mental abilities, including finger tapping, simple mathematics questions (addition, subtraction, multiplication, division), recall of numbers, and recall of objects. It should take 15 minutes to complete these tests. At the end of the study visit, you will complete 1 questionnaire that asks if you think the study drug/placebo is helping you, and how satisfied you are with the study. It should take about 5 minutes to complete the questionnaire. Length of Study: You will be on this study for up to 3 hours. You will be taken off study if intolerable side effects occur during the study. This is an investigational study. Fentanyl is FDA approved and commercially available for the treatment of pain. Its use to help with shortness of breath is investigational. Up to 25 patients will be enrolled in this study. All will be enrolled at MD Anderson.

Official Title
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A Preliminary Study of Prophylactic Fentanyl Pectin Nasal Spray (FPNS) for Exercise-Induced Breakthrough Dyspnea

Conditions
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Advanced Cancers

Intervention / Treatment
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* Drug: Fentanyl Pectin Nasal Spray
* Drug: Placebo Nasal Spray
* Other: Walk Test
* Behavioral: Questionnaires
* Behavioral: Mental Ability Tests


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of cancer Breakthrough dyspnea, defined in this study as dyspnea on exertion with an average intensity level >=3/10 on the numeric rating scale Outpatient at MD Anderson Cancer Center seen by the Supportive Care Service or Thoracic Medical Oncology Ambulatory and able to walk with or without walking aid On strong opioids with morphine equivalent daily dose of 80-500 mg, with stable (i.e. +/- 30%) regular dose over the last 24 hours Karnofsky performance status >=50% Age 18 or older Able to complete study assessments Exclusion Criteria: Dyspnea at rest >=7/10 at the time of enrollment Supplemental oxygen requirement >6 L per minute Delirium (i.e. Memorial delirium rating scale >13) History of unstable angina or myocardial infarction 1 month prior to study enrollment Resting heart rate >120 at the time of study enrollment Systolic pressure >180 mmHg or diastolic pressure >100 mmHg at the time of study enrollment History of active opioid abuse within the past 12 months History of allergy to fentanyl Unwilling to provide informed consent Patients who currently have no evidence of disease

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fentanyl Pectin Nasal Spray<br>Fentanyl pectin nasal (FPNS) dose equivalent to 15-25% of the morphine equivalent daily dose (MEDD). FPNS administered intranasally 20 minutes before the second 6-minute walk test. Same dose repeated at least 30 minutes after the first dose and 20 minutes prior to the third and final 6 minute walk test. Walk test administered before first dose of FPNS. Participant will rest for 30 minutes after walk test. FPNS administered, then participant will wait 20 minutes before repeating second 6 minute walk test. After second walk test, participant will rest for 30 minutes. FPNS administered for second time, then participant will wait for 20 minutes. Walk test administered again for 6 minutes. Questionnaires completed at baseline, before each walk test, and at end of final walk test. Four mental ability tests administered after each walk test to include finger tapping, simple mathematics questions, recall of numbers, and recall of objects. | Drug: Fentanyl Pectin Nasal Spray<br>* Fentanyl pectin nasal (FPNS) dose equivalent to 15-25% of the morphine equivalent daily dose (MEDD) administered intranasally 20 minutes before the second 6-minute walk test. Same dose repeated at least 30 minutes after the first dose and 20 minutes prior to the third and final 6 minute walk test.<br>Other: Walk Test<br>* Walk test administered before first dose of drug/placebo nasal spray. Participant will rest for 30 minutes after walk test. Drug/placebo nasal spray administered, then participant will wait 20 minutes before repeating second 6 minute walk test. After second walk test, participant will rest for 30 minutes. Drug/placebo nasal spray administered for second time, then participant will wait for 20 minutes. Walk test administered again for 6 minutes.<br>Behavioral: Questionnaires<br>* Questionnaires completed at baseline, before each walk test, and at end of final walk test.<br>* Other names: Surveys;Behavioral: Mental Ability Tests<br>* Four mental ability tests administered after each walk test to include finger tapping, simple mathematics questions, recall of numbers, and recall of objects.<br>|
| Placebo Comparator: Placebo Nasal Spray<br>Placebo nasal spray administered intranasally 20 minutes before the second 6-minute walk test. Same dose repeated at least 30 minutes after the first dose and 20 minutes prior to the third and final 6 minute walk test. Walk test administered before first dose of placebo nasal spray. Participant will rest for 30 minutes after walk test. Placebo nasal spray administered, then participant will wait 20 minutes before repeating second 6 minute walk test. After second walk test, participant will rest for 30 minutes. Placebo nasal spray administered for second time, then participant will wait for 20 minutes. Walk test administered again for 6 minutes. Questionnaires completed at baseline, before each walk test, and at end of final walk test. Four mental ability tests administered after each walk test to include finger tapping, simple mathematics questions, recall of numbers, and recall of objects. | Drug: Placebo Nasal Spray<br>* Placebo nasal spray administered intranasally 20 minutes before the second 6-minute walk test. Same dose repeated at least 30 minutes after the first dose and 20 minutes prior to the third and final 6 minute walk test.<br>Other: Walk Test<br>* Walk test administered before first dose of drug/placebo nasal spray. Participant will rest for 30 minutes after walk test. Drug/placebo nasal spray administered, then participant will wait 20 minutes before repeating second 6 minute walk test. After second walk test, participant will rest for 30 minutes. Drug/placebo nasal spray administered for second time, then participant will wait for 20 minutes. Walk test administered again for 6 minutes.<br>Behavioral: Questionnaires<br>* Questionnaires completed at baseline, before each walk test, and at end of final walk test.<br>* Other names: Surveys;Behavioral: Mental Ability Tests<br>* Four mental ability tests administered after each walk test to include finger tapping, simple mathematics questions, recall of numbers, and recall of objects.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dyspnea Numeric Rating Scale | Our primary outcome was dyspnea intensity now using a dyspnea numeric rating scale that ranges from 0 (no shortness of breath) to 10 (worst possible shortness of breath). Measured the mean difference of dyspnea numeric rating scale between the first and second 6 Minute Walk Tests and between the first and third 6 Minute Walk Tests. 6 minute walk tests were carried out following guidelines from the American Thoracic Society. | 1.5 to 2 hours on a Single visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dyspnea Borg Scale | Assessed dyspnea using the modified Dyspnea Borg Scale that ranges from 0 (no shortness of breath) to 10 (worst possible shortness of breath). Measured the mean difference of modified Dyspnea Borg scale between the first and second 6 Minute Walk Tests and between the first and third 6 Minute Walk Tests. | 1.5 to 2 hours on a Single visit | 
| Walk Distance at 6 Minutes | Compared the mean difference of distance between the first and second 6 Minute Walk Tests and between the first and third 6 Minute Walk Tests. | 1.5 to 2 hours on a Single visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced Cancers, Exercise-Induced Breakthrough Dyspnea, Shortness of breath, Fentanyl pectin nasal spray, Placebo nasal spray, Walk test, Questionnaires, Surveys, Mental ability tests