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Head and Neck CancerPhase 2NCT04221165

Opioid Therapy vs Multimodal Analgesia in Head and Neck Cancer

A Phase 2 study testing Opioids and PAiN - multimodal analgesia in people with Head and Neck Cancer and Radiation-Induced Mucositis, run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's at 1 site in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Opioids and PAiN - multimodal analgesia
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
49 participants
Where
1 siteCanada
Study dates
4 Aug 2020to 15 Sep 2023
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 10Show fewer
  • 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

Who cannot join

  • 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
Show all 13Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

Canada1 site
  • London Regional Cancer Program of the Lawson Health Research Institute

    London, Ontario, N6A 4L6

Other trials in Canada

About this study

Official title: 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.

Read the 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.

Being tested
Opioids, PAiN - multimodal analgesia
Keywords
Pain, Analgesia
Medical subject headings
Head and Neck Neoplasms, Pain, Agnosia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • OpioidsDrug

    Opioids will be prescribed as per institutional standards.

  • PAiN - multimodal analgesiaDrug

    PAiN: Pregabalin, Acetaminophen, Naproxen, pantoprazole magnesium

Study groups in NCT04221165
Study groupRoleWhat they receive
Opioid AnalgesiaActive comparatorOpioids will be prescribed as per institutional standards. Examples of opioids are morphine and hydromorphone.
Receives: Drug: Opioids
Multimodal AnalgesiaExperimentalPregabalin (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)
Receives: Drug: PAiN - multimodal analgesia

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Approximately 2 years and 3 months

Secondary outcomes (12)
  1. 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.

    Measured: Approximately 2 years and 4 months

  2. Duration of Opioid Requirement

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

    Measured: Approximately 2 years and 6 months

  3. 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.

    Measured: Approximately 2 years and 4 months

  4. 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).

    Measured: Approximately 24 months, 27 months, and 30 months

  5. 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.

    Measured: Approximately 24 months, 27 months, and 30 months

  6. 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.

    Measured: Approximately 2 years and 4 months

  7. Hospital Admissions

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

    Measured: Approximately 27 months and 30 months

  8. Time to Feeding Tube Insertion

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

    Measured: Approximately 2 years and 3 months

  9. Weight Loss

    Weight loss from randomization to the end of radiation treatment.

    Measured: Approximately 2 years and 3 months

  10. Rates of Common Terminology Criteria for Adverse Events Toxicities

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

    Measured: Approximately 2 years and 6 months

  11. Treatment Interruptions

    Number of participants with radiation of chemotherapy treatment interruptions.

    Measured: Approximately 2 years and 6 months

  12. Death

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

    Measured: Approximately 2 years and 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Jan 2020
  2. Study start4 Aug 2020
  3. Primary completion15 Sep 2023
  4. Study completion15 Sep 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Supportive care
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
49 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04221165
Sponsor's protocol ID
OPTIMAL HN
Status last verified
Feb 2024
First submitted
6 Jan 2020
Last updated
28 Feb 2024
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 30990535
  • 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.

    PubMed 24615748
  • 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.

    PubMed 26712589
  • 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.

    PubMed 26849016
  • Zayed S, Lang P, Read N, Correa RJM, Mutsaers A, Goodman CD, D'Angelo K, Kieraszewicz K, Vanwynsberghe D, Kingsbury-Paul A, Crewdson K, Neeb J, Carreau C, Winquist E, Kuruvilla S, Stewart P, Moulin DE, Warner A, Palma DA. Opioid therapy vs. Multimodal analgesia in head and neck cancer (OPTIMAL-HN): Results of a randomized clinical trial. Radiother Oncol. 2025 May;206:110831. doi: 10.1016/j.radonc.2025.110831. Epub 2025 Mar 5.

    PubMed 40054624
  • 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.

    PubMed 33740977

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Opioids and PAiN - multimodal analgesia in people with Head and Neck Cancer and Radiation-Induced Mucositis, run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's at 1 site in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Average Pain Rating measured on the 11 Numeric Rating Scale (time frame: Approximately 2 years and 3 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04221165, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Feb 2024.

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