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

Study Overview
=================
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 significant pain relief (reduction of Numeric Rating Scale (NRS) of 50%) and 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 time to achieve significant pain relief 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%

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

Conditions
-----------------
Pain, Cancer of Head and Neck

Intervention / Treatment
-----------------
* Drug: fentanyl
* Drug: methadone


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: fentanyl<br>active pain treatment with fentanyl patch | Drug: fentanyl<br>* 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%<br>* Other names: Durogesic;|
| Experimental: methadone<br>active pain treatment with methadone | Drug: methadone<br>* 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%<br>* Other names: Symoron;|

What is the study measuring?
-----------------
Primary Outcome Measures

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

Secondary Outcome Measures

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

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Pain, Cancer of Head and Neck, methadone, Fentanyl