Fentanyl Buccal Tablet for the Relief of Episodic Breathlessness in Cancer Patients

NCT04635852 | Completed Phase 2 DMC

• 3 other identifiers: Uni-Koeln-14122011-005797-32DRKS00004353
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 3

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.

Conditions

Cancer; Dyspnea, Paroxysmal

Outcome Measures

Primary Outcomes (1)

• Time to onset of meaningful breathlessness relief

  To determine the time to onset of meaningful breathlessness relief of fentanyl buccal tablet (FBT) in comparison to immediate-release morphine (IRM)

  minutes (by stop watch) from drug application of FBT/IRM up to breathlessness relief

Secondary Outcomes (4)

• Breathlessness intensity

  at 0, 3, 5, 10, 15, 20, 30, 45 and 60 minutes after application of FBT/IRM

• Numbers of rescue medication doses

  Numbers of rescue medication doses through study completion, assessed at day 10 (final visit)

• Patient's & investigator's satisfaction

  through study completion, day 10 (e.g. final visit)

• Preferences of study drugs

  through study completion, day 10 (e.g. final visit)

Other Outcomes (12)

• Number of (serious) adverse events (AE/SAE; Safety of FBNT/IRM)

  through study completion, day 10 (e.g. final visit)

• Severity of AE/SAE (Safety of FBNT/IRM)

  through study completion, day 10 (e.g. final visit)

• Oxygen saturation (Safety of FBNT/IRM)

  through study completion, day 10 (e.g. final visit)

Study Arms (2)

Fentanyl

EXPERIMENTAL

Fentanyl buccal tablet Dosage: 100µg - 600 µg Fentanyl (to be determined by titration) Administration: buccal administration (tablet)

Drug: Fentanyl

Immediate release morphine

ACTIVE COMPARATOR

Immediate release morphine, solution Dosage: Start with a minimum of 5mg (to be determined by titration)

Drug: Immediate release morphine

Interventions

Fentanyl DRUG

Also known as: Fentanyl buccal tablet, Fentanyl citrate

Fentanyl

Immediate release morphine DRUG

Also known as: Morphine Solution

Immediate release morphine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically proven cancer of any entity which is non-curable as judged by the referring physician or investigator
• To be an inpatient during the study
• 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
• History of recurrent episodic breathlessness - episodic breathlessness is defined as an increase in breathlessness occurring intermittently in patients with or without underlying continuous breathlessness
• Peak intensity of episodic breathlessness ≥ 3 (NRS, 0-10)
• 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
• Life expectancy of at least one month as judged by the referring physician or investigator

You may not qualify if:

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

Sponsors & Collaborators

• University of Cologne: lead
• Teva Branded Pharmaceutical Products R&D, Inc.: collaborator

Study Sites (3)

University Hospital Göttingen Center of Palliative Medicine

Göttingen, Hesse, 37075, Germany

Location

Study Center Palliative Medicine

Cologne, North Rhine-Westphalia, 50937, Germany

Location

Hospital Essen- Mitte, Departement of Palliative Medicine

Essen, North Rhine-Westphalia, 45136, Germany

Location

MeSH Terms

Conditions

Neoplasms; Dyspnea, Paroxysmal

Interventions

Fentanyl

Condition Hierarchy (Ancestors)

Dyspnea; Respiration Disorders; Respiratory Tract Diseases; Heart Failure; Heart Diseases; Cardiovascular Diseases; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Raymond Voltz, Professor

  Department of Palliative Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: prof

Study Record Dates

• First Submitted: January 10, 2014
• First Posted: November 19, 2020
• Study Start: March 1, 2013
• Primary Completion: November 1, 2014
• Study Completion: December 1, 2014
• Last Updated: November 19, 2020

Record last verified: 2020-11

Locations

DE (3)