Clinical trial NCT04221165: Opioid Therapy vs Multimodal Analgesia in Head and Neck Cancer
Official title: Opioid Therapy vs Multimodal Analgesia in Head and Neck Cancer: A Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Head and Neck Cancer
Radiation-Induced Mucositis
Keywords: Pain
Analgesia
Lead sponsor: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
Sponsor class: OTHER
Collaborators: name: Ontario Institute for Cancer Research
First posted: 2020-01-09
Enrollment: 49
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: The purpose of this study is to compare the daily pain level scores for patients taking opioids alone for pain relief, compared with those treated by multimodal analgesia with three medications: pregabalin, naproxen, and acetaminophen, with the ability to switch over to opioid medications if needed. In addition to pain level scores, this study will compare opioid use (length of time and doses taken), quality of life, admissions to hospital, feeding tube requirements, weight loss, and treatment interruptions between these two analgesic regimens.

Detailed description: A significant proportion of patients undergoing radiotherapy alone or chemotherapy and radiotherapy together for their head and neck cancer experience mucositis, which is severe pain in the mouth and throat caused by radiation treatment. Patients often enter a cycle of pain, difficulty swallowing, malnourishment, and reduced quality of life. This may translate into decreased oral intake requiring a feeding tube, and radiation or chemotherapy treatment breaks, which reduce the chance of tumour control and cure.

Currently, opioid therapy is the cornerstone of head and neck cancer pain management. Although effective for pain relief, opioids can have side effects.

As an alternative to opioid treatments, "multimodal analgesia" is a treatment using medications from different classes with different mechanisms of action. Examples of analgesic medications used for multimodal analgesia include medications similar to acetaminophen or ibuprofen, and others.

The primary purpose of this study is to compare pain level scores of patients taking opioids versus patients taking multimodal analgesia.

Eligibility criteria: Inclusion Criteria:

* Age 18 or older
* Willing to provide consent
* Histologically confirmed mucosal head and neck malignancy
* Undergoing chemoradiotherapy or radiotherapy alone with a planned total radiation dose of 50 Gray (Gy) or greater
* Eastern Co-operative Oncology Group (ECOG) performance status 0-2
* Life expectancy \> 6 months
* Onset of 4/10 pain on the 11-Numeric Rating Scale that is localized to the mucosa of the mouth or throat, before or during radiation treatment, that is not caused by a current oral candidiasis infection.
* Ability to take pills, either by mouth or crushed via NasoGastric (NG) tube or Gastrostomy tube (G-tube)
* Ability to complete the study questionnaires and pain diary
* Ability to sign consent without requirement for a substitute decision maker

Exclusion Criteria:

* Skin and salivary gland malignancies
* High daily opioid use at time of enrollment (defined as 30 mg oral morphine equivalent dose or higher)
* Concurrent second active malignancy
* Pregnant or lactating women
* Psychological disorder requiring pharmacologic treatment
* Regular systemic steroid use
* Regular anticonvulsant or antidepressant use
* Renal Impairment (defined as creatinine clearance \< 60 mL/min)
* Liver Dysfunction (defined as total bilirubin \> 34.2 µmol/L)
* Documented true allergy to acetaminophen, NSAIDs, pregabalin or opioids
* History of upper gastrointestinal bleed
* Known bleeding disorder
* History of or current substance use disorder

Primary outcomes:
measure: Average Pain Rating measured on the 11 Numeric Rating Scale
timeFrame: Approximately 2 years and 3 months
Secondary outcomes:
measure: Average Weekly Opioid Use
timeFrame: Approximately 2 years and 4 months
measure: Duration of Opioid Requirement
timeFrame: Approximately 2 years and 6 months
measure: Average Daily 11-Numeric Rating Scale for Pain
timeFrame: Approximately 2 years and 4 months
measure: Quality of Life as measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30)
timeFrame: Approximately 24 months, 27 months, and 30 months
measure: Quality of Life as measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Head & Neck 43 (EORTC QLQ-HN 43)
timeFrame: Approximately 24 months, 27 months, and 30 months
measure: Average Weekly Opioids Dispensed
timeFrame: Approximately 2 years and 4 months
measure: Hospital Admissions
timeFrame: Approximately 27 months and 30 months
measure: Time to Feeding Tube Insertion
timeFrame: Approximately 2 years and 3 months
measure: Weight Loss
timeFrame: Approximately 2 years and 3 months
measure: Rates of Common Terminology Criteria for Adverse Events Toxicities
timeFrame: Approximately 2 years and 6 months
measure: Treatment Interruptions
timeFrame: Approximately 2 years and 6 months
measure: Death
timeFrame: Approximately 2 years and 6 months
Other outcomes:
Locations:
city: London
country: Canada
facility: London Regional Cancer Program of the Lawson Health Research Institute
state: Ontario
Study officials:
affiliation: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
name: David Palma, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Elad S, Yarom N. The Search for an Effective Therapy and Pain Relief for Oral Mucositis. JAMA. 2019 Apr 16;321(15):1459-1461. doi: 10.1001/jama.2019.3269. No abstract available.
citation: Lalla RV, Bowen J, Barasch A, Elting L, Epstein J, Keefe DM, McGuire DB, Migliorati C, Nicolatou-Galitis O, Peterson DE, Raber-Durlacher JE, Sonis ST, Elad S; Mucositis Guidelines Leadership Group of the Multinational Association of Supportive Care in Cancer and International Society of Oral Oncology (MASCC/ISOO). MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy. Cancer. 2014 May 15;120(10):1453-61. doi: 10.1002/cncr.28592. Epub 2014 Feb 25.
citation: Mirabile A, Airoldi M, Ripamonti C, Bolner A, Murphy B, Russi E, Numico G, Licitra L, Bossi P. Pain management in head and neck cancer patients undergoing chemo-radiotherapy: Clinical practical recommendations. Crit Rev Oncol Hematol. 2016 Mar;99:100-6. doi: 10.1016/j.critrevonc.2015.11.010. Epub 2015 Dec 3.
citation: Alfieri S, Ripamonti CI, Marceglia S, Orlandi E, Iacovelli NA, Granata R, Cavallo A, Pozzi P, Boffi R, Bergamini C, Imbimbo M, Pala L, Resteghini C, Mirabile A, Locati LD, Licitra L, Bossi P. Temporal course and predictive factors of analgesic opioid requirement for chemoradiation-induced oral mucositis in oropharyngeal cancer. Head Neck. 2016 Apr;38 Suppl 1:E1521-7. doi: 10.1002/hed.24272. Epub 2016 Feb 5.
citation: Zayed S, Lang P, Mendez LC, Read N, Sathya J, Venkatesan V, Moulin DE, Warner A, Palma DA. Opioid therapy vs. multimodal analgesia in head and neck Cancer (OPTIMAL-HN): study protocol for a randomized clinical trial. BMC Palliat Care. 2021 Mar 19;20(1):45. doi: 10.1186/s12904-021-00735-0.