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

Pain Clinical Trial

— 310111-4  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01317589
• Other study ID #: METC 11-2-007
• Status: Completed
• Phase: Phase 4
• First received: February 16, 2011
• Last updated: July 15, 2015
• Start date: May 2011
• Est. completion date: July 2015

Study information

• Verified date: July 2015
• Source: Maastricht University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial 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?

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%

Recruitment information / eligibility

• Status: Completed
• Enrollment: 134
• Est. completion date: July 2015
• Est. primary completion date: July 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cancer of Head and Neck
• Head and Neck Neoplasms
• Pain

Intervention

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%
• 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%

Locations

Country	Name	City	State
Netherlands	University Hospital Maastricht	Maastricht

Sponsors (1)

Lead Sponsor	Collaborator
Maastricht University Medical Center

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	significant pain relief (reduction of Numeric Rating Scale (NRS) of 50%)		9 weeks	No
Secondary	time to achieve significant pain relief		9 weeks	No
Secondary	side-effect profile		9 weeks	Yes