Fentanyl + Morphine for Shortness of Breath in Cancer

Overseen By David Hui

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: M.D. Anderson Cancer Center

Must be taking: Strong opioids

Must not be taking: Benzodiazepines

Disqualifiers: Substance use disorder, Delirium, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 6

Duration: 19 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether fentanyl (specifically, Fentanyl Citrate Buccal Tablet) or morphine can control shortness of breath in cancer patients during or after physical activity. Both drugs manage pain and might also alleviate cancer-related breathing issues. Participants will receive either fentanyl, morphine, or a placebo to compare effectiveness. The trial seeks cancer patients who experience difficulty breathing during physical tasks and are already on strong pain medication. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop all current medications, but you must not be using scheduled benzodiazepines unless you can stop during the study. You also need to be on a stable dose of strong opioids like morphine.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that both fentanyl buccal tablets and morphine have been safely used in cancer patients. Fentanyl helps alleviate shortness of breath related to physical activity in these patients. However, it can cause serious breathing problems, especially when starting or changing doses.

Morphine also effectively eases shortness of breath in cancer patients. Studies have confirmed its safety, but like fentanyl, it can lead to breathing issues, particularly at the beginning of treatment.

Both medications are opioids, commonly used to manage pain in cancer patients, and their safety is well-documented. Patients considering these treatments should discuss potential risks, especially related to breathing, with their healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they explore new ways to manage shortness of breath in cancer patients by using Fentanyl Citrate Buccal Tablet (FBT) and morphine, each with unique features. Unlike the standard oral or intravenous forms, FBT is administered sublingually, which could offer faster relief by being absorbed directly into the bloodstream through the mouth. Morphine, a long-standing option, is being tested here to see how it compares in efficiency and effectiveness with FBT. These trials could reveal quicker and potentially more effective methods for easing breathlessness, a common and distressing symptom in cancer patients.

What evidence suggests that this trial's treatments could be effective for shortness of breath in cancer patients?

Studies have shown that both fentanyl buccal tablets and morphine can help manage shortness of breath in cancer patients. In this trial, some participants will receive fentanyl buccal tablets. Research indicates that these tablets can reduce difficulty breathing during exercise when taken before physical activity and are generally well-tolerated. Another group will receive oral morphine, which has effectively relieved cancer-related breathing problems, especially for those with lung issues. Opioids like morphine have been shown to be safe and helpful for easing breathing difficulties in patients with lung cancer. Overall, evidence suggests these treatments can effectively manage shortness of breath in this group. ^{1 3 4 6 7}

Who Is on the Research Team?

David Hui

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with active cancer, able to walk and complete assessments. They must live near the centers, speak English or Spanish, be on strong opioids with a stable dose, and experience significant shortness of breath during exertion but not at rest. Exclusions include severe heart issues, high oxygen needs, substance abuse history, certain allergies or conditions.

Inclusion Criteria

My cancer is currently active.

I can complete all required study check-ups and tests.

I have been on strong painkillers at a stable dose for the last week.

Exclusion Criteria

I need more than 6 liters of oxygen per minute.

You have a history of drug abuse or have shown signs of potential opioid misuse.

I have been diagnosed with high blood pressure in the lungs.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either fentanyl buccal tablet, morphine, or placebo and complete shuttle walk tests on specified days

19 days

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Fentanyl Citrate Buccal Tablet
• Morphine

Trial Overview The study compares fentanyl buccal tablets and morphine against a placebo in controlling exertional dyspnea (shortness of breath) in cancer patients. It's a phase II trial that includes quality-of-life assessments to determine how these treatments affect physical activity-related breathing difficulties.

How Is the Trial Designed?

Group I: Group II (shuttle walk test, morphine) Experimental Treatment 4 Interventions

Patients complete shuttle walk test on days 1, 5, 8, 12, 15, and 19. Patients also receive morphine PO daily on days 6-19.

Group II: Group I (shuttle walk test, FBT) Experimental Treatment 4 Interventions

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 III: Group III (shuttle walk test, placebo) Active Control 4 Interventions

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.

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study of 504 advanced cancer patients, those using transdermal fentanyl reported higher overall satisfaction with their pain management compared to those using sustained-release oral morphine.

Patients on transdermal fentanyl experienced significantly fewer and less impactful side effects from their pain medication, which may contribute to their greater satisfaction, despite being older and having lower functioning and well-being scores.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality of life and cancer pain: satisfaction and side effects with transdermal fentanyl versus oral morphine. Payne, R., Mathias, SD., Pasta, DJ., et al.[2022]

In a study involving 66 patients, adherence to established guidelines for titrating MS Contin (controlled-release morphine) resulted in effective pain management, with about 75% of patients reporting no or slight pain by the end of the study.

Only 5% of patients discontinued due to drug-related side effects, indicating that MS Contin is generally well-tolerated; however, there is a need for better management of side effects and consideration of patient-controlled titration to optimize pain relief.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of dosing guidelines for the use of oral controlled-release morphine (MS Contin tablets). Warfield, CA.[2019]

A patient with severe neuralgia experienced respiratory depression after taking a single 20 mg dose of controlled release morphine sulfate (MS Contin), highlighting a potential safety concern with this medication.

The immediate reversal of respiratory depression was achieved with nalorphine chloride, demonstrating the effectiveness of this intervention in managing opioid-related side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Respiratory depression following controlled-release morphine sulfate tablets]. Hoogslag, PA., van Dijk, B., Vinks, AA.[2013]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S0885392420306321

Efficacy and Safety of Opioids in Treating Cancer-Related ... In contrast, another RCT conducted by Hui et al22 in 2017 demonstrated oral fentanyl buccal tablets lessened dyspnea versus placebo in this population. Newer ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5705410/

Effect of Prophylactic Fentanyl Buccal Tablet on Episodic ... This study supports that prophylactic FBT was associated with a reduction of exertional dyspnea and was well-tolerated.

3. sciencedirect.com sciencedirect.com/science/article/pii/S088539241300239X

Fentanyl for the Relief of Refractory Breathlessness All studies reported successful relief of breathlessness after fentanyl application, but the only (pilot-) RCT failed to demonstrate a statistically significant ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04188418

Fentanyl Buccal Tablet or Morphine for Exertional Dyspnea ... 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 ...

5. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2776899

Pharmacologic Interventions for Breathlessness in Patients ... This systematic review assesses the benefits and harms of pharmacologic interventions for breathlessness in adults with advanced cancer.

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2007/021947s002lbl.pdf

FENTORATM (fentanyl buccal tablet) Each ... Each tablet contains fentanyl citrate equivalent to fentanyl ... The safety of FENTORA has been evaluated in 304 opioid tolerant cancer patients with breakthrough.

7. medlineplus.gov medlineplus.gov/druginfo/meds/a605043.html

Fentanyl: MedlinePlus Drug Information Fentanyl may cause serious or life-threatening breathing problems, especially during the first 24 to 72 hours of your treatment and any time your dose is ...