Back to resultsFentanyl Buccal Tablet or Morphine for Exertional Dyspnea in Cancer Patients
Primary Purpose
Hematopoietic and Lymphoid Cell Neoplasm, Malignant Solid Neoplasm
Status
Recruiting
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Fentanyl Citrate Buccal Tablet
Morphine
Physical Performance Testing
Placebo Administration
Quality-of-Life Assessment
Questionnaire Administration
Sponsored by
About this trial
This is an interventional treatment trial for Hematopoietic and Lymphoid Cell Neoplasm
Eligibility Criteria
Inclusion Criteria:
- 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 60-370 mg for >= 1 week (wk), with stable (i.e. +/- 30%) regular dose over the last 3 days (d)
- Karnofsky performance status >= 40%
- Age >= 18 years (yrs)
- Able to complete study assessments
- Able to speak English or Spanish
- Reside within 50 miles of participating centers
Exclusion Criteria:
- 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 month prior to enrollment
- Resting heart rate > 120 beats/min at enrollment
- Systolic pressure > 180 mmHg or diastolic pressure > 100 mmHg at enrollment
- 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
- Currently prescribed benzodiazepines
- Severe anemia (Hemoglobin [Hb] < 7 g/L) if documented in the last month and not corrected prior to study enrollment
- Bilirubin >=5 x upper limit of normal if documented in the last month and not lowered to < 5 x normal prior to enrollment
- Diagnosis of acute pulmonary embolism within past 2 weeks
- Diagnosis of pulmonary hypertension
- Diagnosis of malignant pleural effusion with therapeutic thoracentesis expected in the next 2 weeks
- Unwilling to provide informed consent
Sites / Locations
- M D Anderson Cancer CenterRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Active Comparator
Arm Label
Group I (shuttle walk test, FBT)
Group II (shuttle walk test, morphine)
Group III (shuttle walk test, placebo)
Arm Description
Patients complete shuttle walk test on days 1, 5, 8, 12, 15, and 19. Patients also receive FBT sublingually daily on days 6-19.
Patients complete shuttle walk test on days 1, 5, 8, 12, 15, and 19. Patients also receive morphine PO daily on days 6-19.
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
SWT distance
Will be analyzed using linear mixed effects models similar to the primary analysis.
Dyspnea unpleasantness
Will be analyzed using linear mixed effects models similar to the primary analysis.
Daily dyspnea intensity and unpleasantness
Will be analyzed using linear mixed effects models similar to the primary analysis.
Personalized daily activity
Will be analyzed using linear mixed effects models similar to the primary analysis.
Oxygen cost diagram
Will be analyzed using linear mixed effects models similar to the primary analysis.
Symptom burden Questionnaires
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
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
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
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
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
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
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
Will be measured using the Patient Reported Outcomes Measurement Information System (PROMIS) dyspnea instruments.
Full Information
NCT ID
NCT04188418
First Posted
November 14, 2019
Last Updated
June 21, 2023
Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT04188418
Brief Title
Fentanyl Buccal Tablet or Morphine for Exertional Dyspnea in Cancer Patients
Official Title
Efficacy and Safety of Rapid-Onset Opioids for Exertional Dyspnea in Cancer Patients
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 23, 2020 (Actual)
Primary Completion Date
August 31, 2025 (Anticipated)
Study Completion Date
August 31, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)
4. Oversight
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
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hematopoietic and Lymphoid Cell Neoplasm, Malignant Solid Neoplasm
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
150 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Group I (shuttle walk test, FBT)
Arm Type
Experimental
Arm Description
Patients complete shuttle walk test on days 1, 5, 8, 12, 15, and 19. Patients also receive FBT sublingually daily on days 6-19.
Arm Title
Group II (shuttle walk test, morphine)
Arm Type
Experimental
Arm Description
Patients complete shuttle walk test on days 1, 5, 8, 12, 15, and 19. Patients also receive morphine PO daily on days 6-19.
Arm Title
Group III (shuttle walk test, placebo)
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Fentanyl Citrate Buccal Tablet
Other Intervention Name(s)
Fentora
Intervention Description
Given transmucosally
Intervention Type
Drug
Intervention Name(s)
Morphine
Intervention Description
Given PO
Intervention Type
Other
Intervention Name(s)
Physical Performance Testing
Other Intervention Name(s)
Physical Fitness Testing, Physical Function Testing
Intervention Description
Complete shuttle walk test
Intervention Type
Other
Intervention Name(s)
Placebo Administration
Intervention Description
Given PO
Intervention Type
Other
Intervention Name(s)
Quality-of-Life Assessment
Other Intervention Name(s)
Quality of Life Assessment
Intervention Description
Ancillary studies
Intervention Type
Other
Intervention Name(s)
Questionnaire Administration
Intervention Description
Ancillary studies
Primary Outcome Measure Information:
Title
Change in modified Borg scale dyspnea intensity before and after the Shuttle Walk Test (SWT)
Description
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.
Time Frame
Days 5, 8, 12, 15, and 19
Secondary Outcome Measure Information:
Title
SWT distance
Description
Will be analyzed using linear mixed effects models similar to the primary analysis.
Time Frame
Days 5, 8, 12, 15, and 19
Title
Dyspnea unpleasantness
Description
Will be analyzed using linear mixed effects models similar to the primary analysis.
Time Frame
Days 5, 8, 12, 15, and 19
Title
Daily dyspnea intensity and unpleasantness
Description
Will be analyzed using linear mixed effects models similar to the primary analysis.
Time Frame
Days 1-19
Title
Personalized daily activity
Description
Will be analyzed using linear mixed effects models similar to the primary analysis.
Time Frame
Days 1-4, 6-7, 9-11, 13-14, and 16-18
Title
Oxygen cost diagram
Description
Will be analyzed using linear mixed effects models similar to the primary analysis.
Time Frame
Days 1-19
Title
Symptom burden Questionnaires
Description
Will be measured by the Edmonton Symptom Assessment System and analyzed using linear mixed effects models similar to the primary analysis.
Time Frame
Days 1-19
Title
Quality of life Questionnaires
Description
Will be measured by the EuroQol-5 Dimension-5 Level Questionnaire and analyzed using linear mixed effects models similar to the primary analysis.
Time Frame
Days 1-19
Title
Neurocognitive function
Description
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.
Time Frame
Up to day 19
Title
Addictive potential
Description
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.
Time Frame
Up to day 19
Title
Frequency, severity, and interference of adverse effects
Description
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.
Time Frame
Up to day 19
Title
Total opioid dose
Description
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.
Time Frame
Up to day 19
Title
Number of rescue doses per day
Description
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.
Time Frame
Up to day 19
Title
Dyspnea severity and functional impairment
Description
Will be measured using the Patient Reported Outcomes Measurement Information System (PROMIS) dyspnea instruments.
Time Frame
Day 1, 5, 12, 19
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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 60-370 mg for >= 1 week (wk), with stable (i.e. +/- 30%) regular dose over the last 3 days (d)
Karnofsky performance status >= 40%
Age >= 18 years (yrs)
Able to complete study assessments
Able to speak English or Spanish
Reside within 50 miles of participating centers
Exclusion Criteria:
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 month prior to enrollment
Resting heart rate > 120 beats/min at enrollment
Systolic pressure > 180 mmHg or diastolic pressure > 100 mmHg at enrollment
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
Currently prescribed benzodiazepines
Severe anemia (Hemoglobin [Hb] < 7 g/L) if documented in the last month and not corrected prior to study enrollment
Bilirubin >=5 x upper limit of normal if documented in the last month and not lowered to < 5 x normal prior to enrollment
Diagnosis of acute pulmonary embolism within past 2 weeks
Diagnosis of pulmonary hypertension
Diagnosis of malignant pleural effusion with therapeutic thoracentesis expected in the next 2 weeks
Unwilling to provide informed consent
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
David Hui
Phone
713-792-6085
Email
dhui@mdanderson.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David Hui
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
David Hui
Phone
713-792-6085
Email
dhui@mdanderson.org
First Name & Middle Initial & Last Name & Degree
David Hui
12. IPD Sharing Statement
Links:
URL
http://www.mdanderson.org
Description
M D Anderson Cancer Center
Learn more about this trial
Fentanyl Buccal Tablet or Morphine for Exertional Dyspnea in Cancer Patients
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