Clinical trial NCT04635852: Fentanyl Buccal Tablet for the Relief of Episodic Breathlessness in Cancer Patients
Official title: Effentora® for Dyspnoea - Fentanyl Buccal Tablet for the Relief of Episodic Breathlessness in Cancer Patients: A Multicenter, Open Label, Randomized, Morphine-controlled, Crossover, Phase II-TRIAL
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cancer
Dyspnea, Paroxysmal
Lead sponsor: University of Cologne
Sponsor class: OTHER
Collaborators: name: Teva Branded Pharmaceutical Products R&D, Inc.
First posted: 2020-11-19
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: "Episodic breathlessness (or dyspnea) is one form of chronic refractory breathlessness characterized by a severe worsening of breathlessness intensity or unpleasantness beyond usual fluctuations in the patient's perception. Episodes are time-limited (seconds to hours) and occur intermittently, with or without underlying continuous breathlessness. Episodes may be predictable or unpredictable, depending on whether any trigger(s) can be identified. There is a range of known triggers which can interact (e.g. exertion, emotions, comorbidities or external environment). One episode can be caused by one or more triggers." ( definition by an international expert consensus \[Simon et al. 2013\]). Approximately half of patients with cancer complain about breathlessness with the highest prevalence in pulmonary malignancies. Episodic breathlessness is reported by 81% of breathless cancer patients with significant impairment on quality of life and limitations on activity. Although episodic breathlessness show some similar characteristics like episodes of pain (breakthrough cancer pain, BTCP; median duration 30minutes), they are often shorter: 91% last less than 20minutes (min). Other evidence supports these findings with duration between 2-15minutes which is a real challenge for the treatment of episodic breathlessness. In the majority of cases, episodic breathlessness occur 1-4 times per day and peak intensity is rated moderate or severe.

There is evidence for the effectiveness of opioids for the relief of chronic refractory breathlessness. There is no evaluated and proven standard treatment for the relief of episodic breathlessness at the moment but immediate-release morphine (IRM) as solution or tablet is most frequently used in clinical practice to treat episodic breathlessness. Time to onset of action of IRM is about 20-30min for pain. Fentanyl is a potent opioid and shows good evidence for the treatment of BTCP through its quick onset of action (5-15min) and short duration of action (50-60min). Because of its pharmacodynamic properties fentanyl might be appropriate and effective for the relief of episodic breathlessness. However, the efficacy of fentanyl for the relief of breathlessness and time to onset is unknown.

This pilot study aims to evaluate relative efficacy, feasibility and time to onset of two different opioids (fentanyl and morphine) in order to improve the management of episodic breathlessness.


Eligibility criteria: Inclusion criteria:

1. Histologically or cytologically proven cancer of any entity which is non-curable as judged by the referring physician or investigator
2. To be an inpatient during the study
3. Refractory breathlessness - this study applies only to 'refractory breathlessness ' and is defined: a patient is still breathless although the underlying disease (e.g. lung cancer) or cause of breathlessness (e.g. pleural effusion) is treated optimal as judged by the referring physician or investigator
4. History of recurrent episodic breathlessness - episodic breathlessness is defined as an increase in breathlessness occurring intermittently in patients with or without underlying continuous breathlessness
5. Peak intensity of episodic breathlessness ≥ 3 (NRS, 0-10)
6. Opioid tolerance for at least one day - opioid tolerance is defined: patient who receive per day at least 30mg oral morphine, 15mg oral oxycodone, 4mg oral hydromorphone, 12µg/h transdermal fentanyl or an analgetic equivalent of a different opioid or a different routes of application
7. Life expectancy of at least one month as judged by the referring physician or investigator

Exclusion criteria:

1. Uncontrolled breathlessness (i.e. rapidly worsening breathlessness requiring urgent medical or technical intervention)
2. Uncontrolled performance status (i.e. rapid deterioration of performance status)
3. Consideration of any reason by the referring therapeutic team that the patient is not an appropriate participant of a clinical trial
4. Respiratory depression or preconditions with risk of respiratory depression
5. Acute abdomen or ileus or any situation that drug resorption is not possible
6. Renal dysfunction with creatinine clearance (eGFR) calculated as less than 25 ml/minute
7. Medical history of severe hepatic impairment
8. The use of fentanyl transmucosal products for breakthrough cancer pain (BTCP) during the trial
9. The use of a monoamine oxidase inhibitors within the previous 14 days
10. Treatment with any other investigational drugs within the previous 10 days

Primary outcomes:
measure: Time to onset of meaningful breathlessness relief
timeFrame: minutes (by stop watch) from drug application of FBT/IRM up to breathlessness relief
Secondary outcomes:
measure: Breathlessness intensity
timeFrame: at 0, 3, 5, 10, 15, 20, 30, 45 and 60 minutes after application of FBT/IRM
measure: Numbers of rescue medication doses
timeFrame: Numbers of rescue medication doses through study completion, assessed at day 10 (final visit)
measure: Patient's & investigator's satisfaction
timeFrame: through study completion, day 10 (e.g. final visit)
measure: Preferences of study drugs
timeFrame: through study completion, day 10 (e.g. final visit)
Other outcomes:
measure: Number of (serious) adverse events (AE/SAE; Safety of FBNT/IRM)
timeFrame: through study completion, day 10 (e.g. final visit)
measure: Severity of AE/SAE (Safety of FBNT/IRM)
timeFrame: through study completion, day 10 (e.g. final visit)
measure: Oxygen saturation (Safety of FBNT/IRM)
timeFrame: through study completion, day 10 (e.g. final visit)
measure: Patient's vigilance (Safety of FBNT/IRM)
timeFrame: through study completion, day 10 (e.g. final visit)
measure: Respiratory rate (Safety of FBNT/IRM)
timeFrame: through study completion, day 10 (e.g. final visit)
measure: Enrollment rate (Feasibility of study procedures)
timeFrame: day 10 (e.g. final visit)
measure: Completion rate (Feasibility of study procedure)
timeFrame: day 10 (e.g. final visit)
measure: Drop outs (Feasibility of study procedures)
timeFrame: day 10 (e.g. final visit)
measure: Reasons for rejection of study participation of screened patient (Feasibility of study procedures)
timeFrame: day 10 (e.g. final visit)
measure: Acceptability of study procedures
timeFrame: day 10 (e.g. final visit)
measure: Acceptability of measurement tools
timeFrame: day 10 (e.g. final visit)
measure: Acceptability of rescue procedures
timeFrame: day 10 (e.g. final visit)
Locations:
city: Göttingen
country: Germany
facility: University Hospital Göttingen Center of Palliative Medicine
state: Hessen
city: Cologne
country: Germany
facility: Study Center Palliative Medicine
state: NRW
city: Essen
country: Germany
facility: Hospital Essen- Mitte, Departement of Palliative Medicine
state: NRW
Study officials:
affiliation: Department of Palliative Medicine
name: Raymond Voltz, Professor
role: PRINCIPAL_INVESTIGATOR
References: