Fentanyl Buccal Tablet or Morphine for Exertional Dyspnea in Cancer Patients
- Conditions
- Hematopoietic and Lymphoid Cell NeoplasmMalignant Solid Neoplasm
- Interventions
- Other: Physical Performance TestingOther: Placebo AdministrationOther: Quality-of-Life AssessmentOther: Questionnaire Administration
- Registration Number
- NCT04188418
- Lead Sponsor
- M.D. Anderson Cancer Center
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 150
- 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 60-400 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
- Karnofsky performance status ≥40%
- Age ≥18 yrs
- Able to complete study assessments
- Able to speak English or Spanish
- Reside within 65 miles of participating centers or expected to visit MD Anderson in person at least once a month
- 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 mo prior to enrollment
- Hemodynamic instability requiring hospitalization
- 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
- Using scheduled benzodiazepines at the time of enrollment and cannot stop during the study
- Severe anemia (Hb <7 g/L) if documented in the last month and not corrected prior to study enrollment*
- Bilirubin ≥5x upper limit of normal if documented in the last month and not lowered to <5x normal prior to enrollment*
- Diagnosis of acute pulmonary embolism within past 2 wks
- Diagnosis of pulmonary hypertension
- Diagnosis of malignant pleural effusion with therapeutic thoracentesis expected in the next 2 wks
- Currently pregnant or breastfeeding
- Unwilling to provide informed consent
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group I (shuttle walk test, FBT) Fentanyl Citrate Buccal Tablet 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 I (shuttle walk test, FBT) Questionnaire Administration 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 III (shuttle walk test, placebo) Physical Performance Testing 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. Group III (shuttle walk test, placebo) Quality-of-Life Assessment 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. Group I (shuttle walk test, FBT) Physical Performance Testing 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 (shuttle walk test, morphine) Physical Performance Testing Patients complete shuttle walk test on days 1, 5, 8, 12, 15, and 19. Patients also receive morphine PO daily on days 6-19. Group I (shuttle walk test, FBT) Quality-of-Life Assessment 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 (shuttle walk test, morphine) Quality-of-Life Assessment Patients complete shuttle walk test on days 1, 5, 8, 12, 15, and 19. Patients also receive morphine PO daily on days 6-19. Group II (shuttle walk test, morphine) Questionnaire Administration Patients complete shuttle walk test on days 1, 5, 8, 12, 15, and 19. Patients also receive morphine PO daily on days 6-19. Group III (shuttle walk test, placebo) Placebo Administration 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. Group III (shuttle walk test, placebo) Questionnaire Administration 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. Group II (shuttle walk test, morphine) Morphine Patients complete shuttle walk test on days 1, 5, 8, 12, 15, and 19. Patients also receive morphine PO daily on days 6-19.
- Primary Outcome Measures
Name Time Method Change in modified Borg scale dyspnea intensity before and after the Shuttle Walk Test (SWT) Days 5, 8, 12, 15, and 19 Will first determine whether the three treatment groups are different; if so, will test the three pairwise comparisons with intention-to-treat analyses. Repeated-measures analysis of variance (ANOVA) will be implemented using linear mixed effects models with the difference in intervention period SWT modified Borg scale dyspnea intensity before and after SWT as the response variable and the treatment group and observation period SWT measures as predictor variables.
- Secondary Outcome Measures
Name Time Method SWT distance Days 5, 8, 12, 15, and 19 Will be analyzed using linear mixed effects models similar to the primary analysis.
Quality of life Questionnaires Days 1-19 Will be measured by the EuroQol-5 Dimension-5 Level Questionnaire and analyzed using linear mixed effects models similar to the primary analysis.
Dyspnea severity and functional impairment Day 1, 5, 12, 19 Will be measured using the Patient Reported Outcomes Measurement Information System (PROMIS) dyspnea instruments.
Dyspnea unpleasantness Days 5, 8, 12, 15, and 19 Will be analyzed using linear mixed effects models similar to the primary analysis.
Oxygen cost diagram Days 1-19 Will be analyzed using linear mixed effects models similar to the primary analysis.
Daily dyspnea intensity and unpleasantness Days 1-19 Will be analyzed using linear mixed effects models similar to the primary analysis.
Personalized daily activity Days 1-4, 6-7, 9-11, 13-14, and 16-18 Will be analyzed using linear mixed effects models similar to the primary analysis.
Symptom burden Questionnaires Days 1-19 Will be measured by the Edmonton Symptom Assessment System and analyzed using linear mixed effects models similar to the primary analysis.
Neurocognitive function Up to day 19 Will perform paired t-test or ANOVA if the data are normally distributed and the Wilcoxon rank-sum test or Kruskal-Wallis if the data are non-normal.
Frequency, severity, and interference of adverse effects Up to day 19 Will be measured by the Patient-Reported Outcomes Common Terminology Criteria for Adverse Events (PRO-CTCAE). Will perform paired t-test or ANOVA if the data are normally distributed and the Wilcoxon rank-sum test or Kruskal-Wallis if the data are non-normal.
Total opioid dose Up to day 19 Will perform paired t-test or ANOVA if the data are normally distributed and the Wilcoxon rank-sum test or Kruskal-Wallis if the data are non-normal.
Addictive potential Up to day 19 Will be measured by the Drug Effects Questionnaire. Will perform paired t-test or ANOVA if the data are normally distributed and the Wilcoxon rank-sum test or Kruskal-Wallis if the data are non-normal.
Number of rescue doses per day Up to day 19 Will perform paired t-test or ANOVA if the data are normally distributed and the Wilcoxon rank-sum test or Kruskal-Wallis if the data are non-normal.
Trial Locations
- Locations (1)
M D Anderson Cancer Center
🇺🇸Houston, Texas, United States