Head and Neck Squamous Cell CarcinomaPhase 2NCT04752384
Transdermal Buprenorphine for the Treatment of Radiation-Induced Mucositis Pain in Head and Neck Cancer Patients
A Phase 2 study testing Buprenorphine, Tramadol and Oral Mucositis (OM) Pain App in people with Head and Neck Squamous Cell Carcinoma, run by Medical College of Wisconsin at 1 site in United States.
Trial summary
This is a single-arm prospective clinical trial to determine the safety and feasibility of using transdermal buprenorphine in alleviation of radiation induced mucositis pain in head and neck cancer patients. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Head and Neck Squamous Cell Carcinoma
- What is being tested?
- Buprenorphine, Tramadol and Oral Mucositis (OM) Pain App
- Type of treatment
- Pill or oral medicine, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Jul 2021to 4 Apr 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients aged 18-80 years.
- Histologically confirmed malignancies involving the oral cavity, oropharynx, hypopharynx and larynx (including non-squamous cell histologies, salivary gland carcinomas and unknown primary tumors).
- Undergoing a course of either definitive radiation (dose of at least 50 Gy to the head and neck region) +/-chemotherapy or adjuvant radiation (at least 50 Gy to the head and neck region) +/- chemotherapy (Patients with a history of prior definitive course of radiation will be allowed).
- Eastern Cooperative Oncology Group (ECOG) Performance status ≤ 2
- Concurrent enrollment on interventional trial is allowed.
- English speaking and literate
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- Patients will be allowed to take radiotherapy mix, viscous lidocaine or magic mouthwash like agents that do not contain opioids. Tylenol allowed for fever and mild pain before starting drug regimen.
- Adequate organ function: Minor dose adjustments for tramadol is required in severe liver and renal impairment so we would only include patients with adequate organ function outlined in below. No dose adjustment for renal or hepatic impairment is required for TD buprenorphine. Some other parameters like hemoglobin, platelets and white blood count (WBC) are required for administration of standard of care chemotherapy like cisplatin along with radiation in treatment of head and neck squamous cell carcinoma (HNSCC). They are not required for administration of buprenorphine or tramadol.
- total bilirubin < 2 mg/dL
- aspartate aminotransferase (AST) / alanine aminotransferase (ALT) < 5 times institutional upper limit
- creatinine clearance > 30 mL/min/1.73 m2 for patients with creatinine levels above institutional normal"
- Pregnancy: It is known that standard of care treatments of HNSCC radiation therapy and chemotherapy have detrimental effects on human pregnancy or development of the embryo or fetus. Therefore, female patients participating in this study should avoid becoming pregnant, and male patients should avoid impregnating a female partner. Non-sterilized female patients of reproductive age and male patients should use effective methods of contraception through defined periods during and after study treatment as specified below.
- Female patients must meet one of the following:
- Postmenopausal for at least one year before the screening visit, or
- Surgically sterile, or
- If they are of childbearing potential, agree to practice two effective methods of contraception from the time of signing of the informed consent form through three months after the last dose of study drug, AND
- Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, or
- Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, post ovulation methods] and withdrawal are not acceptable contraception methods.)
- Male patients, even if surgically sterilized (i.e., status post vasectomy), must agree to one of the following:
- Practice effective barrier contraception during the entire study treatment period and through 90 days after the last study drug dose, OR
- Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, OR
- Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, post ovulation methods] and withdrawal are not acceptable methods of contraception.)
- Ability to understand a written informed consent document, and the willingness to sign it.
- Possession of a smart phone (android or apple-based platforms) and ability to operate a smart phone application. Patients who do not have smart phones will be provide wireless devices that have OM pain app installed on them.
Who cannot join
- Physical exam demonstrating preexisting mucositis.
- Preexisting oral infection or ongoing toxicity from prior radiotherapy.
- History of substance abuse, positive urine drug screen in last six months.
- Patients with multiple distant metastasis (subjects with resectable oligometastasis will be allowed)
- Current or recent use (within four weeks of screening) of mixed opioid agonists/antagonists or other opioid antagonists. Methadone use within four weeks of screening.
- History of prolonged QTc>greater than 450 milliseconds in males and greater than 470 milliseconds in females.
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- Patients on systemic therapy (chemotherapy or immunotherapy) for another cancer subtype.
- Patients receiving induction chemotherapy prior to or after radiation/chemoradiation like patients with nasopharyngeal carcinoma
- Patients with history of abdominal surgery within 60 days of registration, acute gastrointestinal conditions like colitis and appendicitis within four weeks of screening.
- Patients with conditions that may compromise blood-brain barrier permeability. The blood-brain barrier may become leaky in select neurological diseases, such as amyotrophic lateral sclerosis, epilepsy, brain trauma and edema
- Patients with a history of myocardial infarction ≤ 6 months prior to registration.
- Patients with h/o significant respiratory depression; acute or severe bronchial asthma; known or suspected gastrointestinal obstruction, including paralytic ileus.
- History of serious or severe hypersensitivity reaction to buprenorphine or tramadol or any of its excipients.
- Patients on anti-depressant and anti-psychotic therapy
- Pregnant and lactating women are excluded from this study because chemotherapy and radiation given for treatment of HNSCC has a potential for teratogenic or abortifacient effects. Additionally, Buprenorphine is classified as category C for use during pregnancy, which means that the risk of adverse effects on the fetus cannot be ruled out. Buprenorphine does cross the placenta, and the use of opioids during pregnancy may result in neonatal withdrawals soon after birth. Symptoms of this may include irritability, apnea, increased tone, tremor, convulsions, or respiratory depression in the neonate. The onset of withdrawal in a neonate whose mother has taken buprenorphine during the pregnancy could be anywhere from the first day of life to the eighth day of life.
- Patients with history of seizure disorder as oral tramadol may reduce seizure threshold.
Trial locations and contacts
1 site in 1 country.
United States1 site
Froedtert & the Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
About this study
Official title: Transdermal Buprenorphine for the Treatment of Radiation-Induced Mucositis Pain in Head and Neck Cancer Patients: A Pilot Study
This is a single-arm prospective clinical trial to determine the safety and feasibility of using transdermal buprenorphine in alleviation of radiation induced mucositis pain in head and neck cancer patients.
Read the detailed description
Hypothesis: Long-acting transdermal buprenorphine (FDA-approved dose from 5 mcg to 20 mcg /week) in conjunction with oral tramadol (50mg-400mg) as needed for breakthrough pain would lead to significant reduction in mucositis-related pain in locally advanced head and neck cancer patients being treated with radiation therapy by the end of treatment and follow up period of 12 weeks.
This is a single-arm, interventional, supportive care clinical trial for head and neck cancer patients evaluating role of transdermal (TD) buprenorphine and tramadol combination in alleviating radiation-induced mucositis pain. This will generate preliminary data to test the feasibility and efficacy of study drug regimen. The study will also test the clinical usefulness of the smart phone pain app in recording and reporting radiation induced mucositis pain.
- Conditions
- Head and Neck Squamous Cell Carcinoma
- Being tested
- Buprenorphine, Tramadol, Oral Mucositis (OM) Pain App
- Keywords
- Mucositis, Radiation, Chemoradiation, visual analog scale, Buprenorphine, Tramadol, Brief Pain Inventory, Oral Mucositis Pain App
- Medical subject headings
- Squamous Cell Carcinoma of Head and Neck, Mucositis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BuprenorphineDrug
Also called Belbuca, Probuphine, Buprenex
Transdermal buprenorphine will be started at 5 mcg/hr once a week. Depending on the Visual Analog Scale (VAS) score, it may be increased up to 20 mcg/hr once a week.
TramadolDrug
Also called Ultram, Ryzolt, ConZip
Oral tramadol will be started at 50 mg/day. Depending on the Visual Analog Scale (VAS) score, it may be increased up to 400 mg/day.
Oral Mucositis (OM) Pain AppDevice
Also called OM Pain App
Each study participant will be issued an Android smartphone, or he or she may use his/her own compatible device (whether or not it has an active data service) to which the OM Pain App will be downloaded and installed. Subjects will receive a preprogrammed alarm four times a day from their smartphones prompting them to directly enter OM pain levels on the device. Patients may submit as many pain entries as they wish beyond the four minimum levels.
Subjects will receive a preprogrammed alarm four times a day from their smartphones prompting them to directly enter OM pain levels on the device. Patients may submit as many pain entries as they wish beyond the four minimum levels.
| Study group | Role | What they receive |
|---|---|---|
| Drug Treatment | Experimental | The main objective of this study is to provide preliminary evidence that FDA approved dose of transdermal buprenorphine in conjunction with oral tramadol can provide adequate analgesia of radiation-induced mucositis pain during treatment and follow up period in head and neck cancer patients. Receives: Drug: Buprenorphine; Drug: Tramadol; Device: Oral Mucositis (OM) Pain App |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Number of Subjects Who Achieve at Least a 30 Percent Decrease in Pain From Baseline in VAS Pain Score Calculated From BPI Questionnaire.
The Brief Pain Inventory - Short Form (BPI-sf) is a nine-item self-administered questionnaire used to evaluate the severity of a patient's pain and the impact of this pain on the patient's daily functioning. The patient is asked to rate their worst, least, average, and current pain intensity -- 0 being no pain and 10 being the pain as bad as you can imagine (within the previous 24 hours).
Measured: Baseline up to Week 9
Secondary outcomes (1)
The Number of Subjects Who Achieve at Least a 30 Percent Decrease in Pain From Baseline in Average Daily Pain Score Calculated by OM Pain App.
The Oral Mucositis (OM) Pain App is a smartphone application that was designed to permit subjects to key in pain severity using a visual analog 0-10 scale. The amount of pain that a subject feels ranges across a continuum from none (0) to an extreme amount of pain (10). The App is programed with an alarm to prompt the patient to record pain severity at prescribed intervals daily and through spontaneous patient input. Compliance is measured by subjects entering in a value four times a day into the OM Pain App.
Measured: Baseline up to Week 9
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Feb 2021
- Study start8 Jul 2021
- Primary completion4 Apr 2024
- Study completion4 Apr 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Head and Neck Squamous Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by Medical College of WisconsinThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical College of Wisconsin
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Stuart Wong, Medical College of Wisconsin
- Investigators
- Stuart J. Wong, MD, Principal investigator, Medical College of Wisconsin
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04752384
- Sponsor's protocol ID
- PRO00040100
- Status last verified
- Apr 2025
- First submitted
- 10 Feb 2021
- Last updated
- 20 Apr 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Transdermal Buprenorphine for the Treatment of Radiation-Induced Mucositis Pain in Head and Neck Cancer Patients: A Pilot Study
- ClinicalTrials.gov ID
- NCT04752384
- Acronym / sponsor ID
- PRO00040100
- Conditions
- Head and Neck Squamous Cell Carcinoma
- Keywords
- Mucositis, Radiation, Chemoradiation, visual analog scale, Buprenorphine, Tramadol, Brief Pain Inventory, Oral Mucositis Pain App
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Medical College of WisconsinUniversity, hospital or other
- Study start
- 8 Jul 2021 (actual)
- Primary completion
- 4 Apr 2024 (actual)
- Study completion
- 4 Apr 2024 (actual)
- First posted
- 12 Feb 2021 (actual)
- Results
- Posted 20 Apr 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a single-arm prospective clinical trial to determine the safety and feasibility of using transdermal buprenorphine in alleviation of radiation induced mucositis pain in head and neck cancer patients.
Detailed description
Hypothesis: Long-acting transdermal buprenorphine (FDA-approved dose from 5 mcg to 20 mcg /week) in conjunction with oral tramadol (50mg-400mg) as needed for breakthrough pain would lead to significant reduction in mucositis-related pain in locally advanced head and neck cancer patients being treated with radiation therapy by the end of treatment and follow up period of 12 weeks.
This is a single-arm, interventional, supportive care clinical trial for head and neck cancer patients evaluating role of transdermal (TD) buprenorphine and tramadol combination in alleviating radiation-induced mucositis pain. This will generate preliminary data to test the feasibility and efficacy of study drug regimen. The study will also test the clinical usefulness of the smart phone pain app in recording and reporting radiation induced mucositis pain.
Study design
- Primary purpose
- Supportive care
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Drug Treatment | Experimental | Drug: Buprenorphine, Drug: Tramadol, Device: Oral Mucositis (OM) Pain AppThe main objective of this study is to provide preliminary evidence that FDA approved dose of transdermal buprenorphine in conjunction with oral tramadol can provide adequate analgesia of radiation-induced mucositis pain during treatment and follow up period in head and neck cancer patients. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- Patients aged 18-80 years.
- Histologically confirmed malignancies involving the oral cavity, oropharynx, hypopharynx and larynx (including non-squamous cell histologies, salivary gland carcinomas and unknown primary tumors).
- Undergoing a course of either definitive radiation (dose of at least 50 Gy to the head and neck region) +/-chemotherapy or adjuvant radiation (at least 50 Gy to the head and neck region) +/- chemotherapy (Patients with a history of prior definitive course of radiation will be allowed).
- Eastern Cooperative Oncology Group (ECOG) Performance status ≤ 2
- Concurrent enrollment on interventional trial is allowed.
Key exclusion criteria (16 listed)
- Physical exam demonstrating preexisting mucositis.
- Preexisting oral infection or ongoing toxicity from prior radiotherapy.
- History of substance abuse, positive urine drug screen in last six months.
- Patients with multiple distant metastasis (subjects with resectable oligometastasis will be allowed)
- Current or recent use (within four weeks of screening) of mixed opioid agonists/antagonists or other opioid antagonists. Methadone use within four weeks of screening.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BuprenorphineAlso: Belbuca, Probuphine, BuprenexTransdermal buprenorphine will be started at 5 mcg/hr once a week. Depending on the Visual Analog Scale (VAS) score, it may be increased up to 20 mcg/hr once a week. | Drug | Drug Treatment |
| TramadolAlso: Ultram, Ryzolt, ConZipOral tramadol will be started at 50 mg/day. Depending on the Visual Analog Scale (VAS) score, it may be increased up to 400 mg/day. | Drug | Drug Treatment |
| Oral Mucositis (OM) Pain AppAlso: OM Pain AppEach study participant will be issued an Android smartphone, or he or she may use his/her own compatible device (whether or not it has an active data service) to which the OM Pain App will be downloaded and installed. Subjects will receive a preprogrammed alarm four times a day from their smartphones prompting them to directly enter OM pain levels on the device. Patients may submit as many pain entries as they wish beyond the four minimum levels. Subjects will receive a preprogrammed alarm four times a day from their smartphones prompting them to directly enter OM pain levels on the device. Patients may submit as many pain entries as they wish beyond the four minimum levels. | Device | Drug Treatment |
Primary outcome
The Number of Subjects Who Achieve at Least a 30 Percent Decrease in Pain From Baseline in VAS Pain Score Calculated From BPI Questionnaire.
Time frame: Baseline up to Week 9
The Brief Pain Inventory - Short Form (BPI-sf) is a nine-item self-administered questionnaire used to evaluate the severity of a patient's pain and the impact of this pain on the patient's daily functioning. The patient is asked to rate their worst, least, average, and current pain intensity -- 0 being no pain and 10 being the pain as bad as you can imagine (within the previous 24 hours).
1 secondary outcome
The Number of Subjects Who Achieve at Least a 30 Percent Decrease in Pain From Baseline in Average Daily Pain Score Calculated by OM Pain App.
Time frame: Baseline up to Week 9
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Apr 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stuart J. Wong, MD principal investigator
Medical College of Wisconsin
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Buprenorphine, Tramadol and Oral Mucositis (OM) Pain App in people with Head and Neck Squamous Cell Carcinoma, run by Medical College of Wisconsin at 1 site in United States.
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 24 inclusion and 16 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 20 Apr 2025. 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 United States. 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?
Yes. Results are posted in the registry (first posted 20 Apr 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
The Number of Subjects Who Achieve at Least a 30 Percent Decrease in Pain From Baseline in VAS Pain Score Calculated From BPI Questionnaire. (time frame: Baseline up to Week 9). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 20 Apr 2025.