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Opioid Therapy vs Multimodal Analgesia in Head and Neck Cancer

Primary Purpose

Head and Neck Cancer, Radiation-Induced Mucositis

Status
Recruiting
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
Opioids
PAiN - multimodal analgesia
Sponsored by
Lawson Health Research Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Head and Neck Cancer focused on measuring Pain, Analgesia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • London Regional Cancer Program of the Lawson Health Research InstituteRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Opioid Analgesia

Multimodal Analgesia

Arm Description

Opioids will be prescribed as per institutional standards. Examples of opioids are morphine and hydromorphone.

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)

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
Duration of Opioid Requirement
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 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.
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).
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.
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.
Hospital Admissions
Hospital admissions for febrile neutropenia, serious infection requiring intravenous antibiotics, gastrointestinal bleeding, myocardial infarction, stroke, and acute kidney injury.
Time to Feeding Tube Insertion
The time to feeding tube insertion (e.g. gastrostomy-tube or nasogastric-tube) after randomization, in days.
Weight Loss
Weight loss from randomization to the end of radiation treatment.
Rates of Common Terminology Criteria for Adverse Events Toxicities
Rates of pre-specified Common Terminology Criteria for Adverse Events (CTCAE) toxicities.
Treatment Interruptions
Number of participants with radiation of chemotherapy treatment interruptions.
Death
Number of participants who die during or within 3 months after completion of radiation treatment.

Full Information

First Posted
January 6, 2020
Last Updated
March 7, 2023
Sponsor
Lawson Health Research Institute
Collaborators
Ontario Institute for Cancer Research
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1. Study Identification

Unique Protocol Identification Number
NCT04221165
Brief Title
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

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 4, 2020 (Actual)
Primary Completion Date
September 1, 2023 (Anticipated)
Study Completion Date
December 1, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Lawson Health Research Institute
Collaborators
Ontario Institute for Cancer Research

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Head and Neck Cancer, Radiation-Induced Mucositis
Keywords
Pain, Analgesia

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
62 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Opioid Analgesia
Arm Type
Active Comparator
Arm Description
Opioids will be prescribed as per institutional standards. Examples of opioids are morphine and hydromorphone.
Arm Title
Multimodal Analgesia
Arm Type
Experimental
Arm Description
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)
Intervention Type
Drug
Intervention Name(s)
Opioids
Intervention Description
Opioids will be prescribed as per institutional standards.
Intervention Type
Drug
Intervention Name(s)
PAiN - multimodal analgesia
Intervention Description
PAiN: Pregabalin, Acetaminophen, Naproxen, pantoprazole magnesium
Primary Outcome Measure Information:
Title
Average Pain Rating measured on the 11 Numeric Rating Scale
Description
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.
Time Frame
Approximately 2 years and 3 months
Secondary Outcome Measure Information:
Title
Average Weekly Opioid Use
Description
The average weekly total opioid dose in oral morphine equivalent dosing from randomization to 6 weeks after completion of radiation treatment.
Time Frame
Approximately 2 years and 4 months
Title
Duration of Opioid Requirement
Description
The time from the start of opioid treatment after randomization to the time of stopping opioid analgesia, in days.
Time Frame
Approximately 2 years and 6 months
Title
Average Daily 11-Numeric Rating Scale for Pain
Description
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.
Time Frame
Approximately 2 years and 4 months
Title
Quality of Life as measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30)
Description
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).
Time Frame
Approximately 24 months, 27 months, and 30 months
Title
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)
Description
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.
Time Frame
Approximately 24 months, 27 months, and 30 months
Title
Average Weekly Opioids Dispensed
Description
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 Frame
Approximately 2 years and 4 months
Title
Hospital Admissions
Description
Hospital admissions for febrile neutropenia, serious infection requiring intravenous antibiotics, gastrointestinal bleeding, myocardial infarction, stroke, and acute kidney injury.
Time Frame
Approximately 27 months and 30 months
Title
Time to Feeding Tube Insertion
Description
The time to feeding tube insertion (e.g. gastrostomy-tube or nasogastric-tube) after randomization, in days.
Time Frame
Approximately 2 years and 3 months
Title
Weight Loss
Description
Weight loss from randomization to the end of radiation treatment.
Time Frame
Approximately 2 years and 3 months
Title
Rates of Common Terminology Criteria for Adverse Events Toxicities
Description
Rates of pre-specified Common Terminology Criteria for Adverse Events (CTCAE) toxicities.
Time Frame
Approximately 2 years and 6 months
Title
Treatment Interruptions
Description
Number of participants with radiation of chemotherapy treatment interruptions.
Time Frame
Approximately 2 years and 6 months
Title
Death
Description
Number of participants who die during or within 3 months after completion of radiation treatment.
Time Frame
Approximately 2 years and 6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
David Palma, MD
Phone
519-685-8650
Email
David.Palma@lhsc.on.ca
First Name & Middle Initial & Last Name or Official Title & Degree
Sondos Zayed, MD
Phone
519-685-8650
Email
Sondos.Zayed@lhsc.on.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David Palma, MD
Organizational Affiliation
Lawson Health Research Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
London Regional Cancer Program of the Lawson Health Research Institute
City
London
State/Province
Ontario
ZIP/Postal Code
N6A 4L6
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
David Palma, MD
Phone
519-685-8650
Email
David.Palma@lhsc.on.ca
First Name & Middle Initial & Last Name & Degree
David Palma, MD, PhD

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
30990535
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.
Results Reference
background
PubMed Identifier
24615748
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.
Results Reference
background
PubMed Identifier
26712589
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.
Results Reference
background
PubMed Identifier
26849016
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.
Results Reference
background
PubMed Identifier
33740977
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.
Results Reference
derived

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Opioid Therapy vs Multimodal Analgesia in Head and Neck Cancer

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