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Opioid Therapy vs Multimodal Analgesia in Head and Neck Cancer

Phase 2
Completed
Conditions
Head and Neck Cancer
Radiation-Induced Mucositis
Interventions
Drug: Opioids
Drug: PAiN - multimodal analgesia
Registration Number
NCT04221165
Lead Sponsor
Lawson Health Research Institute
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
49
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Opioid AnalgesiaOpioidsOpioids will be prescribed as per institutional standards. Examples of opioids are morphine and hydromorphone.
Multimodal AnalgesiaPAiN - multimodal analgesiaPregabalin (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)
Primary Outcome Measures
NameTimeMethod
Average Pain Rating measured on the 11 Numeric Rating ScaleApproximately 2 years and 3 months

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.

Secondary Outcome Measures
NameTimeMethod
DeathApproximately 2 years and 6 months

Number of participants who die during or within 3 months after completion of radiation treatment.

Average Weekly Opioid UseApproximately 2 years and 4 months

The average weekly total opioid dose in oral morphine equivalent dosing from randomization to 6 weeks after completion of radiation treatment.

Duration of Opioid RequirementApproximately 2 years and 6 months

The time from the start of opioid treatment after randomization to the time of stopping opioid analgesia, in days.

Average Daily 11-Numeric Rating Scale for PainApproximately 2 years and 4 months

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.

Quality of Life as measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30)Approximately 24 months, 27 months, and 30 months

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).

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)Approximately 24 months, 27 months, and 30 months

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.

Average Weekly Opioids DispensedApproximately 2 years and 4 months

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.

Time to Feeding Tube InsertionApproximately 2 years and 3 months

The time to feeding tube insertion (e.g. gastrostomy-tube or nasogastric-tube) after randomization, in days.

Weight LossApproximately 2 years and 3 months

Weight loss from randomization to the end of radiation treatment.

Rates of Common Terminology Criteria for Adverse Events ToxicitiesApproximately 2 years and 6 months

Rates of pre-specified Common Terminology Criteria for Adverse Events (CTCAE) toxicities.

Treatment InterruptionsApproximately 2 years and 6 months

Number of participants with radiation of chemotherapy treatment interruptions.

Hospital AdmissionsApproximately 27 months and 30 months

Hospital admissions for febrile neutropenia, serious infection requiring intravenous antibiotics, gastrointestinal bleeding, myocardial infarction, stroke, and acute kidney injury.

Trial Locations

Locations (1)

London Regional Cancer Program of the Lawson Health Research Institute

🇨🇦

London, Ontario, Canada

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