Nasal Fentanyl for Chronic Cancer Pain (NFCP-2)

An Open Label, Cross-over, Randomized Controlled Multicenter Phase III Study Comparing Standard Oral SR-morphine by the Clock Medications With Self-controlled Nasal Fentanyl for Chronic Cancer Pain Requiring Opioids

Today, patients with cancer pain in need of opioids for moderate to severe pain get long-acting morphine twice a day and morphine tablets taken on demand in addition. This procedure might be based on the assumption that cancer pain is persistent, although the evidence to support whether this assumption applies to all cancer patients is lacking. Some cancer patients might not need a fixed dose of long-acting morphine.

Because of rapid pain relief, the new fentanyl drugs open for the possibility to take an opioid on demand when pain occurs.

A pilot study where 10 patients with cancer pain were treated with a rapid-acting fentanyl nasal spray taken on demand, showed that this treatment was apparently feasible and safe for these patients.

This approach is studied further in NFCP-II. The participants will be treated with rapid-acting fentanyl nasal spray and long-acting morphine in a crossover study. The primary outcome will be patient satisfaction.

The study will consist of a test dose of nasal fentanyl, a dose-finding phase and a treatment phase with either nasal fentanyl taken on demand or slow-released morphine taken twice a day. After 10 days of treatment there is a crossover and the opposite drug is used for the same participant. Morphine tablets can be taken on demand in all phases of the study.

The participants will meet the investigator at inclusion, at the crossover and at the end of treatment. During the study, a diary is filled in by the participants every morning. Questions about pain and side effects are answered. Satisfaction is measured at the crossover and at end of treatment while preference is measured at the end of treatment.

Study Overview

• Status: Withdrawn
• Conditions: Pain; Cancer
• Intervention / Treatment: Drug: intranasal fentanyl spray; Drug: slow release morphine

• Study Type: Interventional
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Cancer disease
2. Adult (older than 18 years)
3. Cancer-related pain > 4 on an 11 point Numerical Rating Scale (NRS)
4. In the need of opioids (step II or III)
5. Able to use nasal drugs.
6. Life expectancy of > 6 months
7. Karnofsky status > = 60
8. Women of child bearing potential must use adequate contraception
9. Informed consent given according to applicable requirements before any trial-related activities.

Exclusion Criteria:

1. Use of opioids for moderate and severe pain
2. History of substance abuse.*
3. Pathological conditions of the nasal cavity as contraindication to nasal fentanyl
4. Renal- or liver- failure, defined as creatinin > 150 and alanine-amino transferase (ALAT) > x 1.5 reference value
5. Sleep apnoea syndrome, severe chronic obstructive lung disease or illnesses leading to severe respiratory depression.
6. Psychiatric disease
7. Neurological disease giving dizziness or sedation
8. Cognitive impairment which makes the patient unable to complete questionnaires or not able to comply with the study procedures.
9. Previous or ongoing facial radiotherapy
10. Recurrent nose bleeding
11. Known hypersensitivity to the active substances or excipients of the study drugs
12. Pregnant or breastfeeding women
13. Treated with monoamine oxidase (MAO) inhibitor within the last 14 days

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: intranasal fentanyl spray; Fentanyl for nasal administration (NF), is supplied as sprays containing a phosphate buffered solution of fentanyl citrate. NF is available in three strengths: 0.5 mg/ml, 1 mg/ml and 2 mg/ml in multiple-dose sprays. The corresponding doses are 50, 100 and 200 µg/puff. NF is applied as one puff in one nostril. One puff defines and equals one dose. Applying a puff to each nostril the upper dose can be increased to 400 µg. The doses used in this study are 50, 100, 200 ad 400µg. Fentanyl may be administered for up to 6 pain episodes/ 24 hours. For each pain episode, a dose of NF is self-administrated in one nostril. If pain relief is not achieved, another dose of NF could be administered in the opposite nostril after 15 minutes.	Drug: intranasal fentanyl spray; Other Names: Instanyl
Active Comparator: slow release morphine; The active substance is released gradually during its transit through the gastrointestinal tract. Slow release (SR) morphine is available in 5, 10, 30, 60, 100 and 200 mg. SR morphine is administered twice a day, usually every twelfth hour.	Drug: slow release morphine; Other Names: Morphine sulphate pentahydrate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the difference in patient reported satisfaction between the two treatment sessions	measured by the Treatment Satisfaction Questionnaire for Medication (TSQM)	13 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient preference (overall; including pain relief, tolerance to adverse effects and convenience) of treatments after finishing the second part of the clinical study	5 point Likert scale	26 days
Overall rating of average pain control in the two treatment phases	measured by an 11- point numeric rating scale	26 days
Overall rating of average side effects in the two treatment phase	measured by an 11-point numeric rate scales	26 days

Collaborators and Investigators

• Sponsor: Norwegian University of Science and Technology
• Collaborators: Maastricht University Medical Center; Fondazione IRCCS Istituto Nazionale dei Tumori, Milano; St. Olavs Hospital; University Hospital, Bonn; Cantonal Hospital of St. Gallen; Flinders University; L'Hospitalet de Llobregat
• Investigators: Study Director: Stein Kaasa, MD prof, Norwegian University of Science and Technology

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2017
• Primary Completion (Actual): December 1, 2020
• Study Completion (Actual): December 1, 2020

Study Registration Dates

• First Submitted: July 19, 2013
• First Submitted That Met QC Criteria: July 19, 2013
• First Posted (Estimate): July 23, 2013

Study Record Updates

• Last Update Posted (Actual): December 10, 2020
• Last Update Submitted That Met QC Criteria: December 8, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: morphine; fentanyl; patient preference; patient satisfaction; administration, intranasal
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Cancer Pain; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Analgesics, Opioid; Narcotics; Adjuvants, Anesthesia; Fentanyl; Morphine
• Other Study ID Numbers: NFCP-2

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No