Fentanyl Buccal Tablet or Morphine for Exertional Dyspnea in Cancer Patients

Malignant Solid Neoplasm Clinical Trial

Official title:

Efficacy and Safety of Rapid-Onset Opioids for Exertional Dyspnea in Cancer Patients

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04188418
• Other study ID #: 2019-0701
• Secondary ID: NCI-2019-0752920
• Status: Recruiting
• Phase: Phase 3
• Start date: October 23, 2020
• Est. completion date: August 31, 2025

Study information

• Verified date: December 2023
• Source: M.D. Anderson Cancer Center
• Contact: David Hui
• Phone: 713-792-6085
• Email: dhui[@]mdanderson.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: August 31, 2025
• Est. primary completion date: August 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Dyspnea
• Hematopoietic and Lymphoid Cell Neoplasm
• Malignant Solid Neoplasm
• Neoplasms

Intervention

Drug:
• Fentanyl Citrate Buccal Tablet
Given transmucosally
• Morphine
Given PO

Other:
• Physical Performance Testing
Complete shuttle walk test
• Placebo Administration
Given PO
• Quality-of-Life Assessment
Ancillary studies
• Questionnaire Administration
Ancillary studies

Locations

Country	Name	City	State
United States	M D Anderson Cancer Center	Houston	Texas

Sponsors (2)

Lead Sponsor	Collaborator
M.D. Anderson Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	SWT distance	Will be analyzed using linear mixed effects models similar to the primary analysis.	Days 5, 8, 12, 15, and 19
Secondary	Dyspnea unpleasantness	Will be analyzed using linear mixed effects models similar to the primary analysis.	Days 5, 8, 12, 15, and 19
Secondary	Daily dyspnea intensity and unpleasantness	Will be analyzed using linear mixed effects models similar to the primary analysis.	Days 1-19
Secondary	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
Secondary	Oxygen cost diagram	Will be analyzed using linear mixed effects models similar to the primary analysis.	Days 1-19
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Dyspnea severity and functional impairment	Will be measured using the Patient Reported Outcomes Measurement Information System (PROMIS) dyspnea instruments.	Day 1, 5, 12, 19

External Links

•   M D Anderson Cancer Center