Opioid Therapy vs Multimodal Analgesia in Head and Neck Cancer

Opioid Therapy vs Multimodal Analgesia in Head and Neck Cancer: A Randomized Clinical Trial

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.

Study Overview

• Status: Completed
• Conditions: Head and Neck Cancer; Radiation-Induced Mucositis
• Intervention / Treatment: Drug: Opioids; Drug: PAiN - multimodal analgesia

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.

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • London, Ontario, Canada, N6A 4L6
      • London Regional Cancer Program of the Lawson Health Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Opioid Analgesia; Opioids will be prescribed as per institutional standards. Examples of opioids are morphine and hydromorphone.	Drug: Opioids; Opioids will be prescribed as per institutional standards.
Experimental: Multimodal Analgesia; Pregabalin (50 mg to 300 mg, oral, twice daily), acetaminophen (1000 mg, oral, 3 times per day), naproxen 250 mg to 500 mg, oral, twice daily), and pantoprazole magnesium (40 mg, oral, daily)	Drug: PAiN - multimodal analgesia; PAiN: Pregabalin, Acetaminophen, Naproxen, pantoprazole magnesium

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average Pain Rating measured on the 11 Numeric Rating Scale	Average pain rating during the last 7 days of radiation therapy, as reported by the patient on the 11-Numeric Rating Scale (11-NRS). On the 11-NRS, zero (0) is no pain, and ten (10) is the worst possible pain.	Approximately 2 years and 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average Weekly Opioid Use	The average weekly total opioid dose in oral morphine equivalent dosing from randomization to 6 weeks after completion of radiation treatment.	Approximately 2 years and 4 months
Duration of Opioid Requirement	The time from the start of opioid treatment after randomization to the time of stopping opioid analgesia, in days.	Approximately 2 years and 6 months
Average Daily 11-Numeric Rating Scale for Pain	Average pain rating from the time of randomization until 6 weeks after completion of radiation treatment, as reported by the patient on the 11-Numeric Rating Scale (11-NRS). On the 11-NRS, zero (0) is no pain, and ten (10) is the worst possible pain.	Approximately 2 years and 4 months
Quality of Life as measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30)	Quality of life, as reported by the patient, will be assessed using the EORTC QLQ-C30 validated questionnaire. Responses regarding function and symptoms are on a scale of 1 (not at all) to 4 (very much). Also included are questions about overall health and quality of life. Responses are on a scale of 1 (very poor) to 7 (excellent).	Approximately 24 months, 27 months, and 30 months
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)	Quality of life, as reported by the patient, will be assessed using the EORTC QLQ-HN 43 validated questionnaire. Responses regarding symptoms or problems are on a scale of 1 (not at all) to 4 (very much). This questionnaire is specifically for patients with head and neck cancer.	Approximately 24 months, 27 months, and 30 months
Average Weekly Opioids Dispensed	The average weekly total opioid dose dispensed by the pharmacy in oral morphine equivalent dosing from randomization to 6 weeks after completion of radiation treatment.	Approximately 2 years and 4 months
Hospital Admissions	Hospital admissions for febrile neutropenia, serious infection requiring intravenous antibiotics, gastrointestinal bleeding, myocardial infarction, stroke, and acute kidney injury.	Approximately 27 months and 30 months
Time to Feeding Tube Insertion	The time to feeding tube insertion (e.g. gastrostomy-tube or nasogastric-tube) after randomization, in days.	Approximately 2 years and 3 months
Weight Loss	Weight loss from randomization to the end of radiation treatment.	Approximately 2 years and 3 months
Rates of Common Terminology Criteria for Adverse Events Toxicities	Rates of pre-specified Common Terminology Criteria for Adverse Events (CTCAE) toxicities.	Approximately 2 years and 6 months
Treatment Interruptions	Number of participants with radiation of chemotherapy treatment interruptions.	Approximately 2 years and 6 months
Death	Number of participants who die during or within 3 months after completion of radiation treatment.	Approximately 2 years and 6 months

Collaborators and Investigators

• Sponsor: Lawson Health Research Institute
• Collaborators: Ontario Institute for Cancer Research
• Investigators: Principal Investigator: David Palma, MD, Lawson Health Research Institute

Publications and helpful links

General Publications

• 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. Erratum In: Cancer. 2015 Apr 15;121(8):1339.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): August 4, 2020
• Primary Completion (Actual): September 15, 2023
• Study Completion (Actual): September 15, 2023

Study Registration Dates

• First Submitted: January 6, 2020
• First Submitted That Met QC Criteria: January 6, 2020
• First Posted (Actual): January 9, 2020

Study Record Updates

• Last Update Posted (Actual): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 26, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Pain; Analgesia
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Diseases; Gastroenteritis; Stomatognathic Diseases; Mouth Diseases; Head and Neck Neoplasms; Mucositis; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Narcotics; Analgesics, Opioid
• Other Study ID Numbers: OPTIMAL HN

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No