Fentanyl Buccal Tablets for Exercise Induced Breakthrough Dyspnea

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.

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