Fentanyl Sublingual Tablet or Morphine for the Control of Shortness of Breath During or After Physical Activity in Cancer Patients
Fentanyl Sublingual Tablet or Morphine for the Control of Shortness of Breath During or After Physical Activity in Cancer Patients
This phase III trial studies fentanyl sublingual (under the tongue) tablet or morphine to see
 how well it works compared to a placebo in controlling shortness of breath during or after
 physical activity in cancer patients. Fentanyl sublingual tablet and morphine are opioids
 normally used to control pain that may also help to prevent or control shortness of breath
 during or after physical activity in cancer patients.
PRIMARY OBJECTIVE:

 I. To compare the effect of prophylactic fentanyl buccal tablet (FBT), morphine sulfate, and
 placebo on the increase in the intensity of exertional dyspnea (0-10 point modified Borg
 scale) measured before versus at the end of a shuttle walk test (SWT).

 SECONDARY OBJECTIVES:

 I. To compare the effects of prophylactic FBT, morphine sulfate, and placebo on SWT distance
 and dyspnea unpleasantness, average daily dyspnea (intensity and unpleasantness, oxygen cost
 diagram), personalized daily activity (ability to complete activity), personalized dyspnea
 response, symptom burden (Edmonton Symptom Assessment System [ESAS]), quality of life
 (EuroQol-5 Dimension-5 Level [EQ-5D-5L]), and dyspnea severity and functional impairment
 based on the Patient Reported Outcomes Measurement Information System (PROMIS) dyspnea
 instruments.

 II. To explore the effects of prophylactic FBT, morphine sulfate, and placebo on
 neurocognitive function, addictive potential (Drug Effects Questionnaire), adverse effects
 (Common Terminology Criteria for Adverse Events [CTCAE], Patient-Reported Outcomes version of
 CTCAE [PRO-CTCAE]), and pattern of opioid use.

 OUTLINE: Patients are randomized to 1 of 3 groups.

 GROUP I: Patients complete shuttle walk test on days 1, 5, 8, 12, 15, and 19. Patients also
 receive FBT sublingually daily on days 6-19.

 GROUP II: Patients complete shuttle walk test on days 1, 5, 8, 12, 15, and 19. Patients also
 receive morphine orally (PO) daily on days 6-19.

 GROUP III: Patients complete shuttle walk test on days 1, 5, 8, 12, 15, and 19. Patients also
 receive placebo (sublingually or PO) daily on days 6-19.
Inclusion Criteria:

 -  Diagnosis of cancer with evidence of active disease

 -  Dyspnea on exertion with an average intensity level >= 4/10 on a modified Borg scale

 -  Outpatient at participating centers

 -  Ambulatory and able to walk, with or without walking aid

 -  On strong opioids with morphine equivalent daily dose (MEDD) of 60-370 mg for >= 1
 week (wk), with stable (i.e. +/- 30%) regular dose over the last 3 days (d)

 -  Karnofsky performance status >= 40%

 -  Able to complete study assessments

 -  Able to speak English or Spanish

 -  Reside within 50 miles of participating centers

 Exclusion Criteria:

 -  Dyspnea at rest >= 7/10 on modified Borg scale at enrollment

 -  Supplemental oxygen requirement > 6 L/min

 -  Delirium (i.e. Memorial Delirium Assessment Scale >= 13)

 -  History of unstable angina or myocardial infarction 1 month prior to enrollment

 -  Resting heart rate > 120 beats/min at enrollment

 -  Systolic pressure > 180 mmHg or diastolic pressure > 100 mmHg at enrollment

 -  History of substance use disorder or abnormal urinary drug screen within the past
 year, or at risk of opioid abuse as determined by Screener and Opioid Assessment for
 Patients with Pain (SOAPP14) >= 7

 -  History of or known allergy to fentanyl or morphine sulfate

 -  Currently prescribed benzodiazepines

 -  Severe anemia (Hemoglobin [Hb] < 7 g/L) if documented in the last month and not
 corrected prior to study enrollment

 -  Bilirubin >=5 x upper limit of normal if documented in the last month and not lowered
 to < 5 x normal prior to enrollment

 -  Diagnosis of acute pulmonary embolism within past 2 weeks

 -  Diagnosis of pulmonary hypertension

 -  Diagnosis of malignant pleural effusion with therapeutic thoracentesis expected in the
 next 2 weeks

 -  Unwilling to provide informed consent