Fentanyl Buccal Tablet or Morphine for Exertional Dyspnea in Cancer Patients

Efficacy and Safety of Rapid-Onset Opioids 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.

Study Overview

• Status: Recruiting
• Conditions: Hematopoietic and Lymphoid Cell Neoplasm; Malignant Solid Neoplasm
• Intervention / Treatment: Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Other: Placebo Administration; Drug: Fentanyl Citrate Buccal Tablet; Other: Physical Performance Testing; Drug: Morphine

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.

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: David Hui; Phone Number: 713-792-6085; Email: DHui@mdanderson.org

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • M D Anderson Cancer Center
      • Contact: David Hui; Phone Number: 713-792-6085; Email: DHui@mdanderson.org
      • Principal Investigator: David Hui

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group I (shuttle walk test, FBT); Patients complete shuttle walk test on days 1, 5, 8, 12, 15, and 19. Patients also receive FBT sublingually daily on days 6-19.	Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Other: Questionnaire Administration; Ancillary studies; Drug: Fentanyl Citrate Buccal Tablet; Given transmucosally; Other Names: Fentora; Other: Physical Performance Testing; Complete shuttle walk test; Other Names: Physical Fitness Testing; Physical Function Testing
Experimental: Group II (shuttle walk test, 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.	Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Other: Questionnaire Administration; Ancillary studies; Other: Physical Performance Testing; Complete shuttle walk test; Other Names: Physical Fitness Testing; Physical Function Testing; Drug: Morphine; Given PO
Active Comparator: Group III (shuttle walk test, placebo); 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.	Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Other: Questionnaire Administration; Ancillary studies; Other: Placebo Administration; Given PO; Other: Physical Performance Testing; Complete shuttle walk test; Other Names: Physical Fitness Testing; Physical Function Testing

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in modified Borg scale dyspnea intensity before and after the Shuttle Walk Test (SWT)	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.	Days 5, 8, 12, 15, and 19

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SWT distance	Will be analyzed using linear mixed effects models similar to the primary analysis.	Days 5, 8, 12, 15, and 19
Dyspnea unpleasantness	Will be analyzed using linear mixed effects models similar to the primary analysis.	Days 5, 8, 12, 15, and 19
Daily dyspnea intensity and unpleasantness	Will be analyzed using linear mixed effects models similar to the primary analysis.	Days 1-19
Personalized daily activity	Will be analyzed using linear mixed effects models similar to the primary analysis.	Days 1-4, 6-7, 9-11, 13-14, and 16-18
Oxygen cost diagram	Will be analyzed using linear mixed effects models similar to the primary analysis.	Days 1-19
Symptom burden Questionnaires	Will be measured by the Edmonton Symptom Assessment System and analyzed using linear mixed effects models similar to the primary analysis.	Days 1-19
Quality of life Questionnaires	Will be measured by the EuroQol-5 Dimension-5 Level Questionnaire and analyzed using linear mixed effects models similar to the primary analysis.	Days 1-19
Neurocognitive function	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.	Up to day 19
Addictive potential	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.	Up to day 19
Frequency, severity, and interference of adverse effects	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.	Up to day 19
Total opioid dose	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.	Up to day 19
Number of rescue doses per day	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.	Up to day 19
Dyspnea severity and functional impairment	Will be measured using the Patient Reported Outcomes Measurement Information System (PROMIS) dyspnea instruments.	Day 1, 5, 12, 19

Collaborators and Investigators

• Sponsor: M.D. Anderson Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: David Hui, M.D. Anderson Cancer Center

Publications and helpful links

Helpful Links

• M D Anderson Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): October 23, 2020
• Primary Completion (Estimated): August 31, 2025
• Study Completion (Estimated): August 31, 2025

Study Registration Dates

• First Submitted: November 14, 2019
• First Submitted That Met QC Criteria: December 3, 2019
• First Posted (Actual): December 5, 2019

Study Record Updates

• Last Update Posted (Actual): December 12, 2023
• Last Update Submitted That Met QC Criteria: December 11, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Neoplasms; Dyspnea; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Analgesics, Opioid; Narcotics; Adjuvants, Anesthesia; Fentanyl; Morphine
• Other Study ID Numbers: 2019-0701 (Other Identifier: M D Anderson Cancer Center); NCI-2019-07529 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); R01CA231471 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No