Evaluation of Efficacy and Mechanisms of an Antiinflammatory Intervention for Chemotherapy Related Mucosal Injury
Status:
Terminated
Trial end date:
2010-08-01
Target enrollment:
Participant gender:
Summary
This study consisted of two parts: the pilot study and the main study. The purpose of the
pilot study is to demonstrate the effectiveness of planned laboratory techniques to assess
for TNF-alpha gene expression from unstimulated saliva, plasma, and mucosal epithelial cells
in patients who have chemotherapy-related stomatitis.
Main Study Description: 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, cancer
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 signaling 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 autologous or allogenic peripheral blood stem cell or
bone marrow transplant will be invited to participate in this study during a regularly
scheduled pre-treatment visit. 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.