Evaluation of Efficacy and Mechanisms of an Antiinflammatory Intervention for Chemotherapy Related Mucosal Injury
NCT ID: NCT00031551
Last Updated: 2017-12-06
Study Results
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View full resultsBasic Information
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TERMINATED
PHASE2
27 participants
INTERVENTIONAL
2002-03-31
2010-08-31
Brief Summary
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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.
Detailed Description
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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) (Registered Trademark), 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 TNFa. Elaboration of the role of inflammatory cell signaling associated with stomatitis and the effect of TNFa may elucidate the mechanisms related to the pathogenesis of stomatitis and to other mucosal conditions.
Patients who are scheduled to receive autologous or allogeneic 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 2.5mg in 20cc mouthwash or placebo 20cc mouthwash, 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. TNFa levels in buccal mucosa, analyzed by real time 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.
Conditions
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Keywords
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
TRIPLE
Study Groups
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Main Study: Etanercept Mouthwash
Etanercept 2.5 mg in 20cc mouthwash is swished and spit by the participant every 6 hours. The experimental mouthwash starts one day before conditioning chemotherapy is administered to the participant and continues until oral pain intensity and stomatitis severity scores are both 0, or by bone marrow transplant (BMT) Day +14, whichever occurs first.
Etanercept
Main Study: Placebo Mouthwash
Placebo 20cc mouthwash is swished and spit by the participant every 6 hours. The placebo mouthwash starts one day before conditioning chemotherapy is administered to the participant and continues until oral pain intensity and stomatitis severity scores are both 0, or by bone marrow transplant day (BMT) Day +14, whichever occurs first.
Placebo
Pilot Study
Participants were enrolled in the pilot study to collect descriptive data about pain perception and laboratory techniques.
No interventions assigned to this group
Interventions
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Etanercept
Placebo
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
2. Able to understand and sign protocol consent or assent
3. Age 16 years or older
Exclusion Criteria
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
16 Years
ALL
No
Sponsors
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National Institute of Nursing Research (NINR)
NIH
Responsible Party
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Principal Investigators
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Jane M Fall-Dickson, PhD
Role: PRINCIPAL_INVESTIGATOR
National Institute of Nursing Research, National Institutes of Health
Locations
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National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States
Greenville Cancer Centers of the Carolinas
Greenville, South Carolina, United States
Countries
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References
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Seto BG, Kim M, Wolinsky L, Mito RS, Champlin R. Oral mucositis in patients undergoing bone marrow transplantation. Oral Surg Oral Med Oral Pathol. 1985 Nov;60(5):493-7. doi: 10.1016/0030-4220(85)90237-3.
Woo SB, Sonis ST, Monopoli MM, Sonis AL. A longitudinal study of oral ulcerative mucositis in bone marrow transplant recipients. Cancer. 1993 Sep 1;72(5):1612-7. doi: 10.1002/1097-0142(19930901)72:53.0.co;2-q.
Dose AM. The symptom experience of mucositis, stomatitis, and xerostomia. Semin Oncol Nurs. 1995 Nov;11(4):248-55. doi: 10.1016/s0749-2081(05)80005-1.
Fall-Dickson JM, Ramsay ES, Castro K, Woltz P, Sportes C. Oral mucositis-related oropharyngeal pain and correlative tumor necrosis factor-alpha expression in adult oncology patients undergoing hematopoietic stem cell transplantation. Clin Ther. 2007;29 Suppl:2547-61. doi: 10.1016/j.clinthera.2007.12.004.
Related Links
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NIH Clinical Center Detailed Web Page
Other Identifiers
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02-NR-0133
Identifier Type: OTHER
Identifier Source: secondary_id
020133
Identifier Type: -
Identifier Source: org_study_id