Opioid Therapy vs Multimodal Analgesia in Head and Neck Cancer

Head and Neck Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04221165
• Other study ID #: OPTIMAL HN
• Status: Completed
• Phase: Phase 2
• Start date: August 4, 2020
• Est. completion date: September 15, 2023

Study information

• Verified date: February 2024
• Source: Lawson Health Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: September 15, 2023
• Est. primary completion date: September 15, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Head and Neck Cancer
• Head and Neck Neoplasms
• Mucositis
• Radiation-Induced Mucositis

Intervention

Drug:
• Opioids
Opioids will be prescribed as per institutional standards.
• PAiN - multimodal analgesia
PAiN: Pregabalin, Acetaminophen, Naproxen, pantoprazole magnesium

Locations

Country	Name	City	State
Canada	London Regional Cancer Program of the Lawson Health Research Institute	London	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
Lawson Health Research Institute	Ontario Institute for Cancer Research

Country where clinical trial is conducted

Canada, 

References & Publications (4)

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. — View 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. — View 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. Erratum In: Cancer. 2015 Apr 15;121(8):1339. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Weight Loss	Weight loss from randomization to the end of radiation treatment.	Approximately 2 years and 3 months
Secondary	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
Secondary	Treatment Interruptions	Number of participants with radiation of chemotherapy treatment interruptions.	Approximately 2 years and 6 months
Secondary	Death	Number of participants who die during or within 3 months after completion of radiation treatment.	Approximately 2 years and 6 months