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

NCT ID: NCT01317589

Last Updated: 2015-07-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 134 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-05-31
• Study Completion Date: 2015-07-31

Brief 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?

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%

Conditions

Pain; Cancer of Head and Neck

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

fentanyl

active pain treatment with fentanyl patch

Group Type: ACTIVE_COMPARATOR

fentanyl

Intervention Type: DRUG

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%

methadone

active pain treatment with methadone

Group Type: EXPERIMENTAL

methadone

Intervention Type: DRUG

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%

Interventions

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%

Intervention Type: 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%

Intervention Type: DRUG

Other Intervention Names

Durogesic; Symoron

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Maastricht University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Maarten van Kleef, MD, PhD

Role: STUDY_CHAIR

Maastricht University Medical Center

Locations

University Hospital Maastricht

Maastricht, , Netherlands

Countries

Netherlands

Other Identifiers

METC 11-2-007

Identifier Type: -

Identifier Source: org_study_id