This study will evaluate the safety and effectiveness of an etanercept (Enbrel) mouthwash in treating stomatitis-a condition that often develops in cancer patients receiving certain chemotherapy-and related pain. Stomatitis is an inflammation of the mucous membranes of the mouth and throat causing redness, swelling, and atrophy of tissues that may lead to ulceration, mouth and throat pain, and decreased quality of life. Etanercept is a new drug that has been approved in injection form for treating rheumatoid arthritis and associated pain.

Patients 16 years of age and older who are receiving chemotherapy under a National Cancer Institute protocol may be eligible for this study. The study may be expanded to include patients at the National Naval Medical Center, the Lombardi Cancer Center at Georgetown University Medical Center, and the Johns Hopkins Oncology Center. Normal volunteers will also be enrolled. Volunteers will be screened with a medical history and possibly a physical examination and blood tests.

Normal volunteers will have a port (small, thin plastic tube) placed in an arm vein for drawing blood (thus avoiding the need for multiple needle sticks). They will swish 4 teaspoons of an etanercept solution in their mouths for 30 seconds and then spit it out. Blood samples will be drawn 5 minutes before and 5 minutes after the rinse, and again 1, 2, 3, and 4 hours later. A total of 12 teaspoons of blood will be collected.

Patients will have the following tests and procedures:

- Dental clinic visit before chemotherapy followed by stem cell or bone marrow transplantation. This visit will include:

- Interview regarding current medications and use of alcohol and cigarettes

- Rating of mouth and throat pain

- Photographs of the inside of the mouth

- Examination of the teeth and gums

- Buccal brush biopsy - For this procedure, the inside of the cheek is brushed gently to collect cells, which will be examined for markers of inflammation.

- Etanercept or placebo treatment. Patients will be randomly assigned to swish 4 teaspoons of an etanercept solution or placebo (look-alike solution with no active ingredient) in their mouths for 30 seconds and then spit it out four times a day. They will start using the mouthwash the day before chemotherapy begins and stop when any stomatitis that has developed has healed and there is no oral or throat pain, or, when they are discharged from the hospital-whichever comes first.

- Treatment evaluations. Baseline (7 days before the stem cell or bone marrow transplant), 2 days before the transplant, at days 2, 5, 7, 9, 12, and 14 after the transplant, or at discharge from the hospital-whichever occurs first. Patients will be evaluated with:

- Rating of mouth and throat pain

- Photographs of the inside of the mouth and examination for stomatitis using a small light

- Buccal biopsy

- Blood sample collection, drawn through the central line during a regularly scheduled blood collection

Phase
Phase II

Stomatitis is defined as inflammation of the mucous membranes of the oral cavity and oropharynx characterized by tissue erythema, edema, and atrophy, often progressing to ulceration. Stomatitis is a biologically complex, multifactorial, treatment-related oral condition experienced by many oncology patients, which often leads to a cascade of negative sequelae including oropharyngeal pain, critical treatment alterations or cessation, and decreased quality of life. The optimal treatment strategies for stomatitis have not been established. There is a critical need to examine the pathogenesis of and to evaluate interventions for stomatitis and related acute oropharyngeal pain in the randomized controlled clinical trial setting using valid and reliable stomatitis assessment tools to both advance the science of cancer treatment-related oral toxicities and improve patient care. Therefore, the purpose of this randomized controlled clinical trial is to elucidate the role of inflammation in stomatitis by testing the effects of a novel tumor necrosis factor (TNF) fusion protein etanercept, (Enbrel, Immunex Corporation, Seattle, WA) on the incidence and severity of stomatitis. The actions of this fusion protein, which binds specifically to TNF preventing its interaction with cellular receptors and altering the inflammatory cascade, may provide insight into the role of inflammation in stomatitis. An etanercept effect is defined as a prevention or amelioration of stomatitis and acute oropharyngeal pain and/or changes in levels of tissue mediators. If stomatitis is primarily a consequence of a mucosal inflammatory response, then we hypothesize that this oral condition will be responsive to binding of TNF(alpha). Elaboration of the role of inflammatory cell signalling associated with stomatitis and the effect of TNF(alpha) may elucidate the mechanisms related to the pathogenesis of stomatitis and to other mucosal conditions.

Patients who are scheduled to receive stomatogenic chemotherapy will be invited to participate in this study during a regularly scheduled pre-treatment visit in the National Institute of Dental and Craniofacial Research Dental Clinic. Written informed consent will be obtained from all participants. Patients will be randomized to receive either etanercept mouthwash or placebo, which will both be administered by protocol schedule. Stomatitis and oropharyngeal pain will be measured at baseline and at specified post-chemotherapy time points corresponding with the predicted stomatitis onset, peak, and healing time course. TNF(alpha) levels in buccal mucosa, analyzed by reverse transcriptase polymerase chain reaction techniques, and blood levels of pro-inflammatory cytokines, growth factors, and inflammatory mediators will also be measured at baseline and at specified post-chemotherapy time points corresponding with the predicted stomatitis onset, peak, and healing time course.

Genders Eligible for Study:  Both

Accepts Healthy Volunteers

Criteria

INCLUSION CRITERIA:
a) Male or female oncology patients who are enrolled in the participating NCI stomatogenic chemotherapy protocols, and are willing to participate in this study concurrently.
b) able to understand and sign protocol consent or assent form.
c) age 16 years or older.
EXCLUSION CRITERIA:
a) Pregnant or lactating females;
b) unable to follow oral rinsing directions;
c) intubation;
d) chronic use of medications confounding assessment of the inflammatory response.
e) pre-existing oral infection, which might maximize the possibility of an infection or sepsis contributing to a drug-related adverse event .

Maryland
      (NINR), 9000 Rockville Pike,  Bethesda,  Maryland,  20892,  United States; Recruiting

Study ID Numbers:  020133; 02-NR-0133
Record last reviewed:  February 9, 2004
Last Updated:  February 9, 2004
Record first received:  March 7, 2002
ClinicalTrials.gov Identifier:  NCT00031551
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2004-11-08