Evaluation of Efficacy and Mechanisms of an Antiinflammatory Intervention for Chemotherapy Related Mucosal Injury
Condition: Stomatitis
MeSH terms: Stomatitis
Intervention: Etanercept; Placebo
Intervention MeSH terms: Etanercept
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 27.0
Sex: All
Minimum age: 16 Years
Healthy volunteers: No
Keywords: Stomatitis; Oropharyngeal pain; TNF; Etanercept; Bone marrow transplantation; Chemotherapy; Cancer; Oral cavity; Oral mucous membranes; Randomized controlled clinical trial; Inflammation

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.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

               1. Male or female oncology patients who are enrolled in participating stomatogenic
                  autologous or allogeneic PBSCT/BMT protocols, and are willing to participate in
                  this study concurrently

               2. Able to understand and sign protocol consent or assent

               3. Age 16 years or older

        EXCLUSION CRITERIA:

          1. Pregnant or lactating females

          2. Unable to follow oral rinsing directions

          3. Intubation

          4. Chronic use of medications confounding assessment of the inflammatory response
             (non-steroidal antiinflammatory drugs, antihistamines, and steroids- with the
             exception of decadron that is commonly used as an antiemetic in the PBSCT/BMT setting)

          5. Pre-existing oral infection or upper respiratory infection that might maximize the
             possibility of an infection or sepsis contributing to a drug-related adverse event

          6. Known hypersensitivity or allergic reaction to etanercept