| Eligibility |
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.
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