Treatment of Pain in Head-and-Neck Cancer Patients: is Methadone More Effective? (310111-4)

Treatment of Pain in Head-and-Neck Cancer Patients: is Methadone More Effective Than Fentanyl?

Background of the study:

Treatment of Pain in Head-and-Neck Cancer Patients:

is methadone more effective than fentanyl?

Pain is a prevalent symptom in patients with cancer. A neuropathic component is seen in one third of the patients. In patients with head-and-neck cancer neuropathic pain is far more prevalent than in a general cancer population: 46-64%. Treatment of neuropathic pain is complex and available treatment modalities achieve (partial) pain relief in only 40-60% of patients. The N-Methyl-D-Aspartate Receptor (NMDAR) plays a central role in the mediation of neuropathic pain. NMDAR blockers could be a new approach to treat neuropathic pain in patients with cancer.

Methadone is a strong opioid but at the same time significant non-competitive NMDA-receptor antagonist qualities have been described. Many small studies and case-reports describe the successful rotation from different strong opioids to methadone. There are no studies that selected patients with (predominantly) neuropathic pain to be treated with methadone, whereas this group of patients is expected to profit from the NMDAR-antagonist properties of methadone.

Objective of the study:

This randomised controlled trial (RCT) aims to investigate whether addition of a NMDAR-antagonist to a strong opioid (methadone) is superior in the treatment of predominantly neuropathic pain over a strong opioid alone (fentanyl) in terms of pain relief and time to achieve significant pain relief.

Study design:

Open label randomised controlled trial

Study population:

opioid naïve patients with histological proven head-and-neck cancer and (partly) neuropathic pain with a NRS score of ≥ 4, age =/> 18 years

Intervention Treatment with methadone or fentanyl patch

Primary study parameters/outcome of the study:

Is methadone more effective than fentanyl in the treatment of pain in patients with head-and-neck cancer with respect to

1. significant pain relief (reduction of Numeric Rating Scale (NRS) of 50%) and
2. pain interference

Secondary study parameters/outcome of the study:

Is methadone superior to fentanyl in the treatment of pain in patients with head-and-neck cancer with respect to

1. time to achieve significant pain relief
2. side-effect profile?

Study Overview

• Status: Completed
• Conditions: Pain; Cancer of Head and Neck
• Intervention / Treatment: Drug: fentanyl; Drug: methadone

Detailed Description

Study design The duration of the study will be 9 weeks. Patients will visit the outpatient clinic 5 times. Patients of MAASTRO clinic will be seen directly before or after the radiation therapy. No extra visits will be necessary.

T= -1: - informed consent

• sort of pain (DN4)
• randomisation

T = 0 - questionnaire 1: demographic variables, disease specific variables, BPI, side effect questions, HADS, QoL

• explain and provide the pain sheet
• start methadone 2 x 2,5 mg or fentanyl patch 12 μg/uur
• breakthrough medication: 50 µg fentanyl nose spray or fentanyl stick 400 µg till 6x/day

T=1 - questionnaire 2: BPI, side effect questions, global perceived effect

1 week - review pain sheet on pain and total rescue doses

• if necessary increase dose strong opioid with 50%

T=2 - questionnaire 2: BPI, side effect questions, global perceived effect 3 weeks - review pain sheet on pain and total rescue doses

• if necessary increase dose strong opioid with 50%
• if necessary decrease dose strong opioid with 30%

T=3 - questionnaire 2: BPI, side effect questions, global perceived effect 5 weeks - review pain sheet on pain and total rescue doses

• if necessary increase dose strong opioid with 50%
• if necessary decrease dose strong opioid with 30%

T = 4 - questionnaire 3: BPI, side effect questions, global perceived effect, QoL

• if necessary increase dose strong opioid with 50%
• if necessary decrease dose strong opioid with 30%

• Study Type: Interventional
• Enrollment (Actual): 134
• Phase: Phase 4

Contacts and Locations

Study Locations

• Netherlands
  • Maastricht, Netherlands, 6202AZ
    • University Hospital Maastricht

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:

• opioid naive patients with histological proven head-and-neck cancer and (partly) neuropathic pain with a NRS score of =/> 4

Exclusion Criteria:

• age under 18
• not being able to read or fill in the questionnaires
• recent operation (less than 7 days)
• women of childbearing potential not using contraception

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: fentanyl; active pain treatment with fentanyl patch	Drug: fentanyl; T = 0; start methadone 2 x 2,5 mg or fentanyl patch 12 μg/uur; breakthrough medication: 50 µg fentanyl nose spray or fentanyl stick 400 µg till 6x/day T=1 1 week; if necessary increase dose strong opioid with 50% T=2 3 weeks; if necessary increase dose strong opioid with 50%; if necessary decrease dose strong opioid with 30% T=3 5 weeks; if necessary increase dose strong opioid with 50%; if necessary decrease dose strong opioid with 30% T = 4 9 weeks; if necessary increase dose strong opioid with 50%; if necessary decrease dose strong opioid with 30%; Other Names: Durogesic
Experimental: methadone; active pain treatment with methadone	Drug: methadone; T = 0; start methadone 2 x 2,5 mg or fentanyl patch 12 μg/uur; breakthrough medication: 50 µg fentanyl nose spray or fentanyl stick 400 µg till 6x/day T=1 1 week; if necessary increase dose strong opioid with 50% T=2 3 weeks; if necessary increase dose strong opioid with 50%; if necessary decrease dose strong opioid with 30% T=3 5 weeks; if necessary increase dose strong opioid with 50%; if necessary decrease dose strong opioid with 30% T = 4 9 weeks; if necessary increase dose strong opioid with 50%; if necessary decrease dose strong opioid with 30%; Other Names: Symoron

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
significant pain relief (reduction of Numeric Rating Scale (NRS) of 50%)	9 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
time to achieve significant pain relief	9 weeks
side-effect profile	9 weeks

Collaborators and Investigators

• Sponsor: Maastricht University Medical Center
• Investigators: Study Chair: Maarten van Kleef, MD, PhD, Maastricht University Medical Center

Study record dates

Study Major Dates

• Study Start: May 1, 2011
• Primary Completion (Actual): July 1, 2015
• Study Completion (Actual): July 1, 2015

Study Registration Dates

• First Submitted: February 16, 2011
• First Submitted That Met QC Criteria: March 16, 2011
• First Posted (Estimate): March 17, 2011

Study Record Updates

• Last Update Posted (Estimate): July 16, 2015
• Last Update Submitted That Met QC Criteria: July 15, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Keywords: Pain; Fentanyl; methadone; Cancer of Head and Neck
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; 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; Respiratory System Agents; Antitussive Agents; Fentanyl; Methadone
• Other Study ID Numbers: METC 11-2-007