Hematopoietic and Lymphoid Cell NeoplasmPhase 3NCT04188418
Fentanyl Buccal Tablet or Morphine for Exertional Dyspnea in Cancer Patients
A Phase 3 study testing Fentanyl Citrate Buccal Tablet, Morphine and Physical Performance Testing in people with Hematopoietic and Lymphoid Cell Neoplasm and Malignant Solid Neoplasm, run by M.D. Anderson Cancer Center at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hematopoietic and Lymphoid Cell Neoplasm, Malignant Solid Neoplasm
- What is being tested?
- Fentanyl Citrate Buccal Tablet, Morphine and Physical Performance Testing
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 150 participants
- Where
- 1 siteUnited States
- Study dates
- 23 Oct 2020to 31 Aug 2027
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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%
Show all 10Show fewer
- 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
Who cannot join
- 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
Show all 15Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the detailed description
PRIMARY OBJECTIVE:
- 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:
- 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.
- Being tested
- Fentanyl Citrate Buccal Tablet, Morphine, Physical Performance Testing, Placebo Administration, Quality-of-Life Assessment
- Medical subject headings
- Hematologic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fentanyl Citrate Buccal TabletDrug
Also called Fentora
Given transmucosally
MorphineDrug
Given PO
Physical Performance TestingOther
Also called Physical Fitness Testing, Physical Function Testing
Complete shuttle walk test
Placebo AdministrationOther
Given PO
Quality-of-Life AssessmentOther
Also called Quality of Life Assessment
Ancillary studies
Questionnaire AdministrationOther
Ancillary studies
| Study group | Role | What they receive |
|---|---|---|
| Group I (shuttle walk test, FBT) | Experimental | Patients complete shuttle walk test on days 1, 5, 8, 12, 15, and 19. Patients also receive FBT sublingually daily on days 6-19. Receives: Drug: Fentanyl Citrate Buccal Tablet; Other: Physical Performance Testing; Other: Quality-of-Life Assessment; Other: Questionnaire Administration |
| Group II (shuttle walk test, morphine) | Experimental | Patients complete shuttle walk test on days 1, 5, 8, 12, 15, and 19. Patients also receive morphine PO daily on days 6-19. Receives: Drug: Morphine; Other: Physical Performance Testing; Other: Quality-of-Life Assessment; Other: Questionnaire Administration |
| Group III (shuttle walk test, placebo) | Active comparator | 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. Receives: Other: Physical Performance Testing; Other: Placebo Administration; Other: Quality-of-Life Assessment; Other: Questionnaire Administration |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Days 5, 8, 12, 15, and 19
Secondary outcomes (13)
SWT distance
Will be analyzed using linear mixed effects models similar to the primary analysis.
Measured: Days 5, 8, 12, 15, and 19
Dyspnea unpleasantness
Will be analyzed using linear mixed effects models similar to the primary analysis.
Measured: 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.
Measured: Days 1-19
Personalized daily activity
Will be analyzed using linear mixed effects models similar to the primary analysis.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Up to day 19
Dyspnea severity and functional impairment
Will be measured using the Patient Reported Outcomes Measurement Information System (PROMIS) dyspnea instruments.
Measured: Day 1, 5, 12, 19
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Dec 2019
- Study start23 Oct 2020
- Primary completion31 Aug 2027 (estimated)
- Study completion31 Aug 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hematopoietic and Lymphoid Cell NeoplasmStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- David Hui, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04188418
- Sponsor's protocol ID
- 2019-0701
- Other IDs
- NCI-2019-07529, 2019-0701, R01CA231471
- Status last verified
- Aug 2026
- First submitted
- 14 Nov 2019
- Last updated
- 11 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Hui D, Pacheco S, Nguyen L, Jennings K, de la Cruz V, Stanton P, Laureano R, Ontai A, Mahler D, Bruera E. Efficacy of fentanyl buccal tablet and morphine for exertional dyspnoea in patients with cancer: a double-blind, placebo-controlled, randomised clinical trial. Thorax. 2026 Mar 13;81(4):344-356. doi: 10.1136/thorax-2025-222970.
PubMed 41115797
Study at a glance
From the registry record, last updated by the sponsor on 11 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Rapid-Onset Opioids for Exertional Dyspnea in Cancer Patients
- ClinicalTrials.gov ID
- NCT04188418
- Acronym / sponsor ID
- 2019-0701
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 23 Oct 2020 (actual)
- Primary completion
- 31 Aug 2027 (estimated)
- Study completion
- 31 Aug 2027 (estimated)
- First posted
- 5 Dec 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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:
- 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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Group I (shuttle walk test, FBT) | Experimental | Drug: Fentanyl Citrate Buccal Tablet, Other: Physical Performance Testing, Other: Quality-of-Life Assessment, Other: Questionnaire AdministrationPatients 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) | Experimental | Drug: Morphine, Other: Physical Performance Testing, Other: Quality-of-Life Assessment, Other: Questionnaire AdministrationPatients 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) | Active comparator | Other: Physical Performance Testing, Other: Placebo Administration, Other: Quality-of-Life Assessment, Other: Questionnaire AdministrationPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Fentanyl Citrate Buccal TabletAlso: FentoraGiven transmucosally | Drug | Group I (shuttle walk test, FBT) |
| MorphineGiven PO | Drug | Group II (shuttle walk test, morphine) |
| Physical Performance TestingAlso: Physical Fitness Testing, Physical Function TestingComplete shuttle walk test | Other | Group I (shuttle walk test, FBT), Group II (shuttle walk test, morphine), Group III (shuttle walk test, placebo) |
| Placebo AdministrationGiven PO | Other | Group III (shuttle walk test, placebo) |
| Quality-of-Life AssessmentAlso: Quality of Life AssessmentAncillary studies | Other | Group I (shuttle walk test, FBT), Group II (shuttle walk test, morphine), Group III (shuttle walk test, placebo) |
| Questionnaire AdministrationAncillary studies | Other | Group I (shuttle walk test, FBT), Group II (shuttle walk test, morphine), Group III (shuttle walk test, placebo) |
Primary outcome
Change in modified Borg scale dyspnea intensity before and after the Shuttle Walk Test (SWT)
Time frame: 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.
13 secondary outcomes
SWT distance
Time frame: Days 5, 8, 12, 15, and 19
Dyspnea unpleasantness
Time frame: Days 5, 8, 12, 15, and 19
Daily dyspnea intensity and unpleasantness
Time frame: Days 1-19
Personalized daily activity
Time frame: Days 1-4, 6-7, 9-11, 13-14, and 16-18
Oxygen cost diagram
Time frame: Days 1-19
Symptom burden Questionnaires
Time frame: Days 1-19
Quality of life Questionnaires
Time frame: Days 1-19
Neurocognitive function
Time frame: Up to day 19
Addictive potential
Time frame: Up to day 19
Frequency, severity, and interference of adverse effects
Time frame: Up to day 19
Total opioid dose
Time frame: Up to day 19
Number of rescue doses per day
Time frame: Up to day 19
Dyspnea severity and functional impairment
Time frame: Day 1, 5, 12, 19
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Aug 2026.
- Derived from this study: PubMed 41115797Hui D, Pacheco S, Nguyen L, Jennings K, de la Cruz V, Stanton P, Laureano R, Ontai A, Mahler D, Bruera E. Efficacy of fentanyl buccal tablet and morphine for exertional dyspnoea in patients with cancer: a double-blind, placebo-controlled, randomised clinical trial. Thorax. 2026 Mar 13;81(4):344-356. doi: 10.1136/thorax-2025-222970.
- M D Anderson Cancer CenterLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David Hui principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Fentanyl Citrate Buccal Tablet, Morphine and Physical Performance Testing in people with Hematopoietic and Lymphoid Cell Neoplasm and Malignant Solid Neoplasm, run by M.D. Anderson Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 11 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in modified Borg scale dyspnea intensity before and after the Shuttle Walk Test (SWT) (time frame: Days 5, 8, 12, 15, and 19). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04188418, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Aug 2026.