Symptoms and General Pathology

All Conditions

Nervous System Diseases

Recurrence

Pain

Breakthrough Pain

Neurologic Manifestations

Adjuvants, Anesthesia

Analgesics

Central Nervous System Depressants

All Drugs and Chemicals

Fentanyl

Morphine

Analgesics, Opioid

Narcotics

Anesthetics

Anesthetics, Intravenous

Anesthetics, General

Hospitalized participants asked to complete a number of surveys at baseline. Participants then receive one single dose of intravenous opioid rescue for their first episode of breakthrough pain, and then receive up to 4 doses of FSS for subsequent episodes of breakthrough pain. Initial FSS starting dose is proportional to the patient's morphine equivalent daily dose (MEDD). Symptom questionnaire completed at baseline and after last dose of FSS while hospitalized. Mental ability tests given while hospitalized 30 minutes after first dose of current pain medication, and 30 minutes after each FSS dose. At the time of discharge, if FSS was helpful in controlling participant's pain, they are then able to continue with FSS use for 1 month. Participants given study diary to document pain level, how many times FSS used, and any side effects experienced each day.

Stage 1: First Pain Episode - Single dose of breakthrough opioid given from existing PCA pump equivalent to 10% of their MEDD.

Second Pain Episode - Single dose of FSS equivalent to 16-32% of MEDD. If not effective at 30 minutes, participant repeats same dose one more time (with a cap of 1600 mcg total; i.e. dose given 30 minutes ago + dose now = 1600 mcg maximum.

Third Pain Episode (at least 4 hours after second episode) - Participant required 2 breakthrough FSS doses for the last episode of breakthrough pain, or if the effective dose has not been identified, he/she will double the last administered dose. If breakthrough pain not effective at 30 minutes, participant repeats same dose one more time (with a cap of 1600 mcg total; i.e. dose given 30 minutes ago + dose now = 1600 mcg maximum).

Stage 2: If FSS successful in hospital, upon discharge, FSS used as first choice of pain medication instead of oral pain medication for pain for up to 4 weeks.

Fentanyl Sublingual Spray (FSS)

Symptom questionnaire completed at baseline and after last dose of FSS while hospitalized. After Day 28, questionnaire completed over the phone about participant's opinion of research study.

Questionnaires

Mental ability tests given while hospitalized 30 minutes after first dose of current pain medication, and 30 minutes after each FSS dose.

Mental Ability Tests

Participants given study diary to document pain level, how many times FSS used, and any side effects experienced each day.

Study Diary

Suresh Reddy, MD

The goal of this clinical research study is to learn if an investigational dose of fentanyl sublingual spray (FSS) can help to control pain in patients with advanced cancer when given in an outpatient and inpatient setting.

Study Visits and Study Drug Administration:

This study has 2 stages. Stage 1 will be completed while you are in the inpatient unit of the hospital and Stage 2 will be completed after you are discharged from the hospital.

Stage 1:

While you are in the hospital, if you have a pain episode, the research nurse will give you a single dose of your current pain medication from your existing infusion pump. You will then be asked to rate your current level of pain . You will also be asked if you are having any side effects at 15 minutes and at 30 minutes after the dose has been administered. You will also complete the 4 tests of mental abilities after about 30 minutes.

If after 1-4 hours you have another episode of pain, you will be given a single dose of FSS. You will spray FSS under your tongue and hold it there for about 30-60 seconds before swallowing. You will be asked about your current level of pain at about 15 minutes and 30 minutes after your dose of FSS. You will also complete the 4 tests of mental abilities after about 30 minutes. If you do not feel any pain relief after 30 minutes, you will spray FSS 1 more time under your tongue and you will repeat the pain and mental ability tests.

If you still do not feel any pain relief after about 4 hours from the last dose of FSS, you will spray a double dose of FSS under your tongue up to 2 times and your pain level and mental abilities will be tested at 15 and 30 minutes after each dose.

You may receive FSS up to 4 times total while you are in the hospital.

After your last dose of FSS, you will complete a questionnaire about how your symptoms are after receiving FSS. This should take about 2 minutes to complete.

End of Stage 1:

If FSS was able to help you control your pain, you will stop taking FSS and go back to receiving your regular pain medication for the rest of your hospital stay. When you are discharged from the hospital, you will continue on to Stage 2 of the study (described below) to receive FSS for up to 4 weeks at home. Before you are sent home, you will also be prescribed pain medication to take in addition to the FSS, if needed. Your doctor will explain how to take this medication before you are discharged.

If FSS was not able to help control your pain, your participation in this study will end and you will continue to be treated with standard pain medications.

Stage 2:

If you are taking part in Stage 2, you will use FSS as your first choice of pain medication instead of oral pain medication for pain for up to 4 weeks. At any time that you have a pain episode, you will spray FSS under your tongue.

You will always have the choice of using the pain medication your doctor prescribed to you as a backup every 2 hours as needed for pain. However, it is very important that you do NOT use the oral pain medications at the same time as FSS. If you still have pain after taking FSS, you must wait at least 2 hours before using your pain medications. After 2 more hours if you have another episode of pain, you may use another dose of FSS for pain relief.

Do not take more than 4 doses of FSS each day.

You will be given a patient diary to write down each day your pain level, how many times you used FSS, and any side effects you may have. You will be called at least 2 times each week by a member of the study staff to discuss your diary and to answer any questions you may have. The study staff will also ask you which pain medication you are using besides FSS, how easy you think it is to use FSS, how effective you think FSS is, and how satisfied you are with your current pain medications. Each phone call should last about 10 minutes.

After Day 28, you will complete a questionnaire over the phone about your opinion of this research study. This should take about 5 minutes to complete.

Length of Study:

Your active participation in this study is over after you complete the last questionnaire. You will be taken off study if intolerable side effects occur or if you are unable to follow study directions.

Follow-Up:

About 30 days after your study visit, you will be called by the study staff and asked how you are feeling and about any side effects you may be having. This call should last about 10 minutes.

This is an investigational study. FSS is FDA approved and commercially available for the treatment of pain in cancer patients. It is considered investigational to use the dose of FSS used in this study and to use FSS both in inpatient and outpatient settings.

About 30 participants will be enrolled in this study. All will take part at MD Anderson.

Sublingual Fentanyl for the Management of Breakthrough Pain

A Preliminary Study of Sublingual Fentanyl for the Management of Breakthrough Pain Analgesia in Patients With Advanced Cancer

To determine the effective dose of Fentanyl sublingual spray in the management of breakthrough pain (4 episodes) in hospitalized patients with advanced cancer receiving continuous opioid infusion in which the first starting dose would be proportional to the patients Morphine Equivalent Daily Dose. It will use Alberta Breakthrough Pain assessment tool with 15 questions.

To estimate the differences in the pain response between intravenous opioid breakthrough and fentanyl sublingual spray at effective dose. Pain will be assessed in a 0-10 numeric rating scale that assesses pain intensity now, where 0=no pain at all, and 10=worst possible.

To determine the safety, tolerability, pattern of use and efficacy of Fentanyl sublingual spray in patients with advanced cancer

INSYS Therapeutics Inc

M.D. Anderson Cancer Center

Fentanyl sublingual spray was administered with a starting dose of 100 mcg up to 1600 mcg maximum for each breakthrough pain.

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Married

Separated/Divorced

Marital status

Some high School

Some College

Completed College

Did not answer

Education

Colon

Gastric

Melanoma

Cholangiocarcinoma

Lymphoma

Cancer Type

Suresh K. Reddy, MD/Professor, Palliative Care Med

Data was not collected due to low accrual and early termination.

Effective Dose of Fentanyl Sublingual Spray (FSS)

Difference Between Intravenous Opioid and Fentanyl Sublingual Spray

Safety, Tolerability, Pattern of Use and Efficacy

Overall Study

Respiratory Tract (Lung and Bronchial) Diseases

Dyspnea

Respiration Disorders

Respiratory Tract Diseases

Signs and Symptoms, Respiratory

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.

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.

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.

Fentanyl Pectin Nasal Spray

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.

Placebo Nasal Spray

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.

Walk Test

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.

David Hui, MD

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.

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.

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

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

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.

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.

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.

Depomed

Each adverse effect was measured using an 11-point numeric rating scale (0=none, 10=worst) before drug administration and immediately after the 2nd 6 minute walk test (approximately 30 minutes later) and immediately again after the 3rd 6 minute walk test (again measured approximately 30 minutes later).

Received Fentanyl Pectin Nasal Spray 20 minutes before 2nd 6 minute walk tests, dose equivalent to 15-25% of total daily opioid dose each time.

Interventional (Fentanyl Pectin Nasal Spray) Second Walk Test

Received similar number of Placebo Spray 20 minutes before 2nd 6 minute walk tests.

Control (Placebo), Second Walk Test

Received Fentanyl Pectin Nasal Spray 20 minutes before 3rd 6 minute walk tests, dose equivalent to 15-25% of total daily opioid dose each time.

Interventional (Fentanyl Pectin Nasal Spray),Third Walk Test

Received similar Placebo Spray 20 minutes before 3rd 6 minute walk tests.

Control (Placebo), Third Walk Test

Received Fentanyl Pectin Nasal Spray 20 minutes before 2nd and 3rd 6 minute walk tests, dose equivalent to 15-25% of total daily opioid dose each time.

Intervention Group (Fentanyl Pectin Nasal Spray)

Received similar number of Placebo Spray 20 minutes before 2nd and 3rd 6 minute walk tests.

Controlled Group (Placebo)

Total

Age, Continuous

High School or less

College

Advanced Degree

GastroIntestinal Cancer

Breast Cancer

Lung Cancer

Genitourinary Cancer

Gynecologic Cancer

Hematologic

Others

Metastatic Stage

Localized/Locally advanced

Cancer Stage

Asthma

COPD

Heart Failure

Comorbidity

Intention to treat analysis participants data

David Hui, MD/ Associate Professor, Palliative Care Medicine

Mean difference between 1st and 2nd walk tests

Mean difference between 1st and 3rd walk tests

Dyspnea Numeric Rating Scale

Dyspnea Borg Scale

Interventional Group (Fentanyl Pectin Nasal Spray)

Control Group (Placebo)

Walk Distance at 6 Minutes

Questionnaires completed at baseline and at end of study visit. Participant performs Shuttle Walk Test before and after receiving low-dose Fentanyl sublingual spray. Four mental ability tests completed after each walk test. Low-dose Fentanyl sprayed into mouth and under tongue one hour after first Shuttle Walk Test.

Questionnaires completed at baseline and at end of study visit. Participant performs Shuttle Walk Test before and after receiving high-dose Fentanyl sublingual spray. Four mental ability tests completed after each walk test. High-dose Fentanyl sprayed into mouth and under tongue one hour after first Shuttle Walk Test.

Low-dose Fentanyl Goup: 15-25% of the morphine equivalent daily dose (MEDD) sprayed into mouth and under tongue one hour after first Shuttle Walk Test.

High-Dose Fentanyl Group: 35-45% of the morphine equivalent daily dose (MEDD) sprayed into mouth and under tongue one hour after first Shuttle Walk Test.

Fentanyl Sublingual Spray

Participants walk back and forth between 2 cones in an indoor hallway for up to 12 minutes. After one hour Fentanyl Spray delivered, then second walk test performed.

Shuttle Walk Test

Questionnaire completed about any breathing problems or other symptoms participant may be having at baseline. End of study questionnaire asks which dose level of study drug participant thinks they received. Participant also completes a questionnaire about how study drug may have helped them and how satisfied they are with the study. It should take about 5 minutes to complete the questionnaire.

After each walk test, participant completes 4 tests of their mental abilities. It should take 15 minutes total to complete these tests.

Thirty days study visit participant called by study staff. This call should last about 10 minutes.

Phone Call

The goal of this clinical research study is to learn if fentanyl can help shortness of breath in cancer patients. Researchers also want to learn if the study drug can help to improve your physical function.

If you agree to take part in this study, the study staff will collect information from your medical record about your age, sex, race, and disease type, as well as how well you are able to perform the normal activities of daily living, any drugs you are taking, and any possible causes of shortness of breath.

Study Groups:

You will be randomly assigned (as in the flip of a coin) to receive either low-dose or high-dose fentanyl spray. This is done because no one knows if one study group is better, the same, or worse than the other group.

Study Visit:

During your study visit, you will complete 2 questionnaires about any breathing problems or other symptoms you may be having. It should take about 10 minutes total to complete these questionnaires.

You will blow into a device called a spirometer a few times to measure your lung function. You will also be asked to inhale into another device called a negative inspiratory force meter (NIF). This device measures the volume of air that can be inhaled after normal breathing.

The study staff will then record your vital signs (heart rate, breathing rate, blood pressure, and your blood-oxygen level). Your blood-oxygen level will be measured with a device that will be clipped gently onto your fingertip). You will then be asked how hard it is to catch your breath and to rate your level of tiredness.

When instructed, you will walk back and forth between 2 cones in an indoor hallway for up to 12 minutes. This is called the Shuttle Walk Test. The purpose of this timed test is to see how far and fast you can walk without stopping for a rest. You will be asked to pivot briskly around the cones and continue back the other way. You may stop this test at any time if you feel you cannot continue.

After that, you will sit down and rest for up to 1 hour. During this time, the study drug will be prepared, and you may be asked at different times how hard it is to catch your breath.

After the rest period, you will be given the fentanyl to spray into your mouth and under your tongue. About 10 minutes later, you will be asked about any side effects you may be having.

At that point, you will perform a second Shuttle Walk Test. Then the study staff will ask you again about any side effects you may be having, your level of tiredness, and how hard it is to catch your breath. Your vital signs will also be measured. The total distance you walked will also be recorded.

After each walk test, you will also be asked to complete 4 tests of your mental abilities, including finger tapping, simple math questions (addition, subtraction, multiplication, division), recall of numbers, and recall of objects. It should take 15 minutes total to complete these tests.

At the end of the study visit, you will be asked which dose level of the study drug you think you received (high-dose or low-dose). You will also complete a questionnaire about how the study drug may have helped you and how satisfied you are with the study. It should take about 5 minutes to complete the questionnaire.

At the end of the study, if you think that taking fentanyl helped to improve your breathing, your doctor will be told, so that you and your doctor may discuss if fentanyl would be helpful to you in the future.

Length of Study:

Your active participation in this study is over after you complete the last questionnaire. You will be taken off study if intolerable side effects occur or if you are unable to follow study directions.

Follow-Up:

Fourteen (14) days after your study visit you will be called by the study staff and asked how you are feeling and about any side effects you may be having. This call should last about 10 minutes.

This is an investigational study. Fentanyl is FDA approved and commercially available for the treatment of pain. Its use to control shortness of breath is investigational.

Up to 30 participants will be enrolled in this study. All will take part at MD Anderson.

Fentanyl Sublingual Spray for Exercise-Induced Breakthrough Dyspnea

A Preliminary Study of Prophylactic Fentanyl Sublingual Spray for Exercise-Induced Breakthrough Dyspnea

The primary outcome was dyspnea intensity "now" using the modified Borg scale, which ranges from 0 ("no shortness of breath") to 10 ("worst possible shortness of breath"). We measured the change in modified dyspnea Borg scale (0-10) between the first and second shuttle walk tests. This scale has been validated in multiple studies, with a minimal clinically significant difference of 1 point.

The modified Borg scale (dyspnea unpleasantness), which ranges from 0 ("no shortness of breath") to 10 ("worst possible shortness of breath"). We measured the change in modified dyspnea Borg scale (0-10) between the first and second shuttle walk tests.

We measured the difference in walk distance (in meters) between the first and second shuttle walk tests.

We measured the difference in walk time (in minutes) between the first and second shuttle walk tests.

The fatigue modified Borg scale, which ranges from 0 ("none") to 10 ("worst"). We measured the change in modified fatigue Borg scale (0-10) between the first and second shuttle walk tests.

Received Fentanyl sublingual spray 10 minutes before performing second shuttle walk test, dose was 35-45% of morphine equivalent daily dose.

Intervention Group (High Dose Fentanyl Sublingual Spray)

Received Fentanyl sublingual spray 10 minutes before performing second shuttle walk test, dose was 15-20% of morphine equivalent daily dose.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Sublingual Fentanyl for the Management of Breakthrough Pain	NCT02514252	Advanced Cancer...	Fentanyl Sublin... Questionnaires Mental Ability ... Study Diary	18 Years -	M.D. Anderson Cancer Center
Fentanyl Pectin Nasal Spray (FNPS) for Exercise-Induced Breakthrough Dyspnea	NCT01832402	Advanced Cancer...	Fentanyl Pectin... Placebo Nasal S... Walk Test Questionnaires Mental Ability ...	18 Years -	M.D. Anderson Cancer Center
Fentanyl Sublingual Spray for Exercise-Induced Breakthrough Dyspnea	NCT02597478	Advanced Cancer...	Fentanyl Sublin... Shuttle Walk Te... Questionnaires Mental Ability ... Phone Call	18 Years -	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for mental ability tests