Advanced Cancers
Conditions
Keywords
Advanced Cancers, Cancer with evidence of active disease, Exercise induced breakthrough dyspnea, Shortness of breath, Fentanyl Buccal Tablets, FBT, Placebo, Walk tests, Questionnaires, Surveys
Brief summary
The goal of this clinical research study is to learn if fentanyl can change perception of shortness of breath in cancer patients. Researchers also want to learn if the study drug can help to improve your physical function. In this study, fentanyl will be compared to a placebo. Fentanyl is commonly used for treatment of cancer pain. 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
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 either receive fentanyl or placebo. You will have an equal chance of being assigned to either group. Neither you nor the study staff will know if you are receiving the study drug or the placebo. However, if needed for your safety, the study staff will be able to find out what you are receiving. Study Visit: During your study visit, the study staff will collect information from your medical record about your age, sex, race, disease type, how well you are able to perform the normal activities of daily living, any drugs you are taking, and possible causes of shortness of breath. You will complete 2 questionnaires. One (1) of them will have questions about any breathing symptoms you may be having, and the other asks about any other symptoms you may be having. It should take about 10 minutes to complete these questionnaires. The study staff will then record your vital signs (heart rate, breathing rate, and the level of air breathed out using a measuring device that will be clipped onto your finger). You will also be asked how hard it is to catch your breath and to rate your level of tiredness. You will then walk back and forth in an indoor corridor for up to 6 minutes. This is called a walk test. You may slow down, stop, and rest at any time you need to. After that, you will sit down and rest for up to 1 hour. During this time, the study drug/placebo will be prepared and you may be asked several times how hard it is to catch your breath. You will then be given a study drug/placebo tablet to put it in between your upper gum and cheek. You will then wait for another 30 minutes, be asked about any side effects you may be having, and repeat the walking 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. During each walk test, you will be asked 6 times how hard it is to catch your breath. How often you stopped and for how long will be recorded. 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 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 fill out 1 questionnaire that asks if you think the study drug/placebo is helping you, how satisfied you are with the study, and which treatment you think you received. It should take about 5 minutes to complete the questionnaire. 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: Thirty (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. Fentanyl is FDA approved and commercially available for the treatment of pain. Its use to control shortness of breath is investigational. Up to 20 participants will be enrolled in this study. All will take part at MD Anderson.
Interventions
Fentanyl buccal tablet given to put in between upper gum and cheek one hour after a six minute walk test.
OTHERPlacebo Buccal Tablet
Placebo buccal tablet given to put in between upper gum and cheek one hour after a six minute walk test.
BEHAVIORALQuestionnaires
Completion of two questionnaires at beginning of study visit. It should take about 10 minutes to complete. At the end of study visit, completion of last questionnaire. It should take about 5 minutes to complete the questionnaire.
Sponsors
Teva Pharmaceuticals USA
M.D. Anderson Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Diagnosis of cancer with evidence of active disease 2. Breakthrough dyspnea, defined in this study as dyspnea on exertion with an average intensity level \>/=3/10 on the numeric rating scale 3. Outpatient at MD Anderson Cancer Center seen by the Supportive Care Service, Thoracic Medical Oncology or Cardiopulmonary Center 4. Ambulatory and able to walk with or without walking aid 5. On strong opioids with morphine equivalent daily dose of 60-130 mg for at least one week, with stable (i.e. +/- 30%) regular dose over the last 24 hours 6. Karnofsky performance status \>/=50% 7. Age 18 or older 8. Able to complete study assessments 9. Must speak and understand English.
Exclusion criteria
1. Dyspnea at rest \>/=7/10 at the time of enrollment 2. Supplemental oxygen requirement \>6 L per minute 3. Delirium (i.e. Memorial delirium rating scale \>13) 4. History of unstable angina or myocardial infarction 1 month prior to study enrollment 5. Resting heart rate \>120 at the time of study enrollment 6. Systolic pressure \>180 mmHg or diastolic pressure \>100 mmHg at the time of study enrollment 7. History of active opioid abuse within the past 12 months 8. History of allergy to fentanyl 9. Severe anemia (Hb \<7g/L) if documented in the last month and not corrected prior to study enrollment\* 10. Bilirubin \>5X Upper limit of normal if documented in the last month and not lowered to \<5x normal prior to study enrollment\* 11. Diagnosis of acute pulmonary embolism within past 2 weeks 12. Diagnosis of pulmonary hypertension 13. Unwilling to provide informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dyspnea Numeric Rating Scale | Baseline to 30 minutes | 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 between the baseline and second 6 minute walk test. 6 minute walk tests were carried out following guidelines from the American Thoracic Society. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Dyspnea Borg Scale | Baseline to 30 minutes | Assessed dyspnea using the 0-10 modified Dyspnea Borg Scale at baseline walk test and after second 6 minute walk test. The Borg scale ranges from 0 (no shortness of breath) to 10 (worst possible shortness of breath). Measured the mean difference between the baseline walk test and second 6 minute walk test. |
| Walk Distance at 6 Minutes | Baseline to 30 minutes | Measured the mean difference between the baseline walk test and second 6 minute walk test. |
Countries
United States
Participant flow
Recruitment details
Adult participants (age\>18) with an active diagnosis of cancer were recruited between May 2014 to May 2016 from the Supportive Care Center outpatient clinic of MD Anderson Cancer Center who met the inclusion and exclusion criteria.
Pre-assignment details
A total of 36 participants enrolled. 22 patients were randomized, 14 patients dropped out before randomization, 3 participants died, 4 had declining Karnofsky Performance Score/hospice, 2 participant's Morphine equivalent daily dose was no longer in range, 1 participant declined and 4 participants were no longer interested in the study.
Participants by arm
| Arm | Count |
|---|---|
| Intervention Group (Fentanyl Buccal Tablet) Received Fentanyl Buccal Tablet 30 minutes before 2nd 6 minute walk test, dose equivalent to 20-50% of their total opioid dose over the past 24 hours. | 9 |
| Controlled Group (Placebo) Received Placebo tablet 30 minutes before 2nd 6 minute walk test. | 11 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Total | Controlled Group (Placebo) | Intervention Group (Fentanyl Buccal Tablet) |
|---|---|---|---|
| Age, Continuous | 55 years | 57 years | 52 years |
| Cancer Stage Locally Advanced | 1 Participants | 1 Participants | 0 Participants |
| Cancer Stage Metastatic Stage | 19 Participants | 10 Participants | 9 Participants |
| Cancer Type Breast Cancer | 3 Participants | 2 Participants | 1 Participants |
| Cancer Type Gastrointestinal Cancer | 3 Participants | 1 Participants | 2 Participants |
| Cancer Type Genitourinary Cancer | 3 Participants | 1 Participants | 2 Participants |
| Cancer Type Gynecologic Cancer | 1 Participants | 1 Participants | 0 Participants |
| Cancer Type Lung Cancer | 8 Participants | 5 Participants | 3 Participants |
| Cancer Type Other | 2 Participants | 1 Participants | 1 Participants |
| Education College and above | 4 Participants | 2 Participants | 2 Participants |
| Education High School or less | 16 Participants | 9 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 2 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 18 Participants | 9 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 15 Participants | 8 Participants | 7 Participants |
| Region of Enrollment United States | 20 participants | 11 participants | 9 participants |
| Sex: Female, Male Female | 12 Participants | 6 Participants | 6 Participants |
| Sex: Female, Male Male | 8 Participants | 5 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 11 |
| other Total, other adverse events | 0 / 9 | 2 / 11 |
| serious Total, serious adverse events | 0 / 9 | 0 / 11 |
Outcome results
Primary
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 between the baseline and second 6 minute walk test. 6 minute walk tests were carried out following guidelines from the American Thoracic Society.
Time frame: Baseline to 30 minutes
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Intervention Group (Fentanyl Buccal Tablet) | Dyspnea Numeric Rating Scale | -2.4 score on a scale |
| Controlled Group (Placebo) | Dyspnea Numeric Rating Scale | -1.1 score on a scale |
Secondary
Dyspnea Borg Scale
Assessed dyspnea using the 0-10 modified Dyspnea Borg Scale at baseline walk test and after second 6 minute walk test. The Borg scale ranges from 0 (no shortness of breath) to 10 (worst possible shortness of breath). Measured the mean difference between the baseline walk test and second 6 minute walk test.
Time frame: Baseline to 30 minutes
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Intervention Group (Fentanyl Buccal Tablet) | Dyspnea Borg Scale | -1.6 score on a scale |
| Controlled Group (Placebo) | Dyspnea Borg Scale | -0.5 score on a scale |
Secondary
Walk Distance at 6 Minutes
Measured the mean difference between the baseline walk test and second 6 minute walk test.
Time frame: Baseline to 30 minutes
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Intervention Group (Fentanyl Buccal Tablet) | Walk Distance at 6 Minutes | -1 meters |
| Controlled Group (Placebo) | Walk Distance at 6 Minutes | 6.7 meters |