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

Summary

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?

Conditions

• Pain
• Cancer of Head and Neck

Interventions

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%

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%

Sponsors & Collaborators

• Maastricht University Medical Center

  lead OTHER

Principal Investigators

• Maarten van Kleef, MD, PhD · Maastricht University Medical Center

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2011-05-31

Primary Completion

2015-07-31

Completion

2015-07-31

Countries

• Netherlands

Study Locations