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

Study Description

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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?

Condition or disease	Intervention/treatment	Phase
Pain; Cancer of Head and Neck	Drug: fentanyl; Drug: methadone	Phase 4

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 Design

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	134 participants
Allocation:	Randomized
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Treatment of Pain in Head-and-Neck Cancer Patients: is Methadone More Effective Than Fentanyl?
Study Start Date :	May 2011
Actual Primary Completion Date :	July 2015
Actual Study Completion Date :	July 2015

Arms and Interventions

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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 Name: 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 Name: Symoron

Outcome Measures

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :

1. significant pain relief (reduction of Numeric Rating Scale (NRS) of 50%) [ Time Frame: 9 weeks ]

Secondary Outcome Measures :

1. time to achieve significant pain relief [ Time Frame: 9 weeks ]
2. side-effect profile [ Time Frame: 9 weeks ]

Eligibility Criteria

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

Netherlands
University Hospital Maastricht
Maastricht, Netherlands, 6202AZ

Sponsors and Collaborators

Maastricht University Medical Center

Investigators

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

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Maastricht University Medical Center
ClinicalTrials.gov Identifier:	NCT01317589 History of Changes
Other Study ID Numbers:	METC 11-2-007
First Posted:	March 17, 2011
Last Update Posted:	July 16, 2015
Last Verified:	July 2015

Keywords provided by Maastricht University Medical Center:

Pain; Cancer of Head and Neck; methadone; Fentanyl

Additional relevant MeSH terms:

Head and Neck Neoplasms; Headache; Neoplasms by Site; Neoplasms; Pain; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Fentanyl; Methadone; Analgesics, Opioid; Narcotics	Central Nervous System Depressants; Physiological Effects of Drugs; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Adjuvants, Anesthesia; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Antitussive Agents; Respiratory System Agents