Hematopoietic and Lymphoid Cell Neoplasm, Malignant Solid Neoplasm
Conditions
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.
Interventions
DRUGFentanyl Citrate Buccal Tablet
Given transmucosally
DRUGMorphine
Given PO
OTHERPhysical Performance Testing
Complete shuttle walk test
OTHERPlacebo Administration
Given PO
OTHERQuality-of-Life Assessment
Ancillary studies
OTHERQuestionnaire Administration
Ancillary studies
Sponsors
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, 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. 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 \<7 g/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 enrollment\* 11. Diagnosis of acute pulmonary embolism within past 2 wks 12. Diagnosis of pulmonary hypertension 13. Diagnosis of malignant pleural effusion with therapeutic thoracentesis expected in the next 2 wks 14. Currently pregnant or breastfeeding 15. Unwilling to provide informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| SWT distance | Days 5, 8, 12, 15, and 19 | Will be analyzed using linear mixed effects models similar to the primary analysis. |
| Dyspnea unpleasantness | Days 5, 8, 12, 15, and 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. |
| Oxygen cost diagram | Days 1-19 | 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| Dyspnea severity and functional impairment | Day 1, 5, 12, 19 | Will be measured using the Patient Reported Outcomes Measurement Information System (PROMIS) dyspnea instruments. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORDavid Hui
M.D. Anderson Cancer Center
Outcome results
None listed