Transdermal Buprenorphine for the Treatment of Radiation-Induced Mucositis Pain in Head and Neck Cancer Patients

NCT04752384 | Completed Phase 2 Results DMC FDA Drug FDA Device

• 1 other identifier: PRO00040100
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Head and Neck Squamous Cell Carcinoma

Keywords

Mucositis; Radiation; Chemoradiation; visual analog scale; Buprenorphine; Tramadol; Brief Pain Inventory; Oral Mucositis Pain App

Outcome Measures

Primary Outcomes (1)

• 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).

  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.

  Baseline up to Week 9

Study Arms (1)

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.

Drug: Buprenorphine; Drug: Tramadol; Device: Oral Mucositis (OM) Pain App

Interventions

Buprenorphine DRUG

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.

Also known as: Belbuca, Probuphine, Buprenex

Drug Treatment

Tramadol DRUG

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.

Also known as: Ultram, Ryzolt, ConZip

Drug Treatment

Oral Mucositis (OM) Pain App DEVICE

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.

Also known as: OM Pain App

Drug Treatment

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Medical College of Wisconsin: lead

Study Sites (1)

Froedtert & the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Mucositis

Interventions

Buprenorphine; Tramadol

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Mouth Diseases; Stomatognathic Diseases

Intervention Hierarchy (Ancestors)

Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Cyclohexanols; Hexanols; Fatty Alcohols; Alcohols; Organic Chemicals; Dimethylamines; Methylamines; Amines; Lipids

Results Point of Contact

• Title: Stuart J. Wong, MD
• Organization: Medical College of Wisconsin

swong@mcw.edu

414-805-4600

Study Officials

• Stuart J. Wong, MD

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: February 10, 2021
• First Posted: February 12, 2021
• Study Start: July 8, 2021
• Primary Completion: April 4, 2024
• Study Completion: April 4, 2024
• Last Updated: April 20, 2025
• Results First Posted: April 20, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)