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

 1. Patients aged 18-80 years.

 2. Histologically confirmed malignancies involving the oral cavity, oropharynx,
 hypopharynx and larynx (including non-squamous cell histologies, salivary gland
 carcinomas and unknown primary tumors).

 3. 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).

 4. Eastern Cooperative Oncology Group (ECOG) Performance status ≤ 2

 5. Concurrent enrollment on interventional trial is allowed.

 6. English speaking and literate

 7. 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.

 8. 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.

 1. total bilirubin < 2 mg/dL

 2. aspartate aminotransferase (AST) / alanine aminotransferase (ALT) < 5 times
 institutional upper limit

 3. creatinine clearance > 30 mL/min/1.73 m2 for patients with creatinine levels
 above institutional normal"

 9. 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.)

 10. Ability to understand a written informed consent document, and the willingness to sign
 it.

 11. 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.

 Exclusion Criteria:

 1. Physical exam demonstrating preexisting mucositis.

 2. Preexisting oral infection or ongoing toxicity from prior radiotherapy.

 3. History of substance abuse, positive urine drug screen in last six months.

 4. Patients with multiple distant metastasis (subjects with resectable oligometastasis
 will be allowed)

 5. 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.

 6. History of prolonged QTc>greater than 450 milliseconds in males and greater than 470
 milliseconds in females.

 7. Patients on systemic therapy (chemotherapy or immunotherapy) for another cancer
 subtype.

 8. Patients receiving induction chemotherapy prior to or after radiation/chemoradiation
 like patients with nasopharyngeal carcinoma

 9. Patients with history of abdominal surgery within 60 days of registration, acute
 gastrointestinal conditions like colitis and appendicitis within four weeks of
 screening.

 10. 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

 11. Patients with a history of myocardial infarction ≤ 6 months prior to registration.

 12. Patients with h/o significant respiratory depression; acute or severe bronchial
 asthma; known or suspected gastrointestinal obstruction, including paralytic ileus.

 13. History of serious or severe hypersensitivity reaction to buprenorphine or tramadol or
 any of its excipients.

 14. Patients on anti-depressant and anti-psychotic therapy

 15. 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.

 16. Patients with history of seizure disorder as oral tramadol may reduce seizure
 threshold.