Fentanyl Buccal Tablet or Morphine for Exertional Dyspnea in Cancer Patients

This phase II trial studies fentanyl buccal 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.

Inclusion Criteria: 1. Diagnosis of cancer with evidence of active disease 2. Dyspnea on exertion with an average intensity level ≥4/10 on a modified Borg scale 3. Outpatient at participating centers 4. Ambulatory and able to walk, with or without walking aid 5. On strong opioids with morphine equivalent daily dose (MEDD) of 60-400 mg for ≥1 wk (i.e. at least 4 out of 7 days), with stable (i.e. ±30%) regular dose over the last 3 d 6. Karnofsky performance status ≥40% 7. Age ≥18 yrs 8. Able to complete study assessments 9. Able to speak English or Spanish 10. Reside within 65 miles of participating centers or expected to visit MD Anderson in person at least once a month Exclusion Criteria: 1. Dyspnea at rest ≥7/10 on modified Borg scale at enrollment 2. Supplemental oxygen requirement \>6 L/min 3. Delirium (i.e. Memorial Delirium Assessment Scale ≥13) 4. History of unstable angina or myocardial infarction 1 mo prior to enrollment 5. Hemodynamic instability requiring hospitalization 6. 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 7. History of or known allergy to fentanyl or morphine sulfate 8. Using scheduled benzodiazepines at the time of enrollment and cannot stop during the study 9. Severe anemia (Hb \