Evaluation of Efficacy and Mechanisms of an Antiinflammatory Intervention for Chemotherapy Related Mucosal Injury

Stomatitis Clinical Trial

Official title:

Evaluation of Efficacy and Mechanisms of an Anti-Inflammatory Intervention for Chemotherapy Related Mucosal Injury

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00031551
• Other study ID #: 020133
• Secondary ID: 02-NR-0133
• Status: Terminated
• Phase: Phase 2
• First received: March 7, 2002
• Last updated: November 1, 2017
• Start date: March 2002
• Est. completion date: August 2010

Study information

• Verified date: November 2017
• Source: National Institutes of Health Clinical Center (CC)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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) (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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 27
• Est. completion date: August 2010
• Est. primary completion date: August 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years and older

Eligibility

• 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

Related Conditions & MeSH terms

• Stomatitis

Intervention

Drug:
• Etanercept

• Placebo

Locations

Country	Name	City	State
United States	National Institutes of Health Clinical Center, 9000 Rockville Pike	Bethesda	Maryland
United States	Greenville Cancer Centers of the Carolinas	Greenville	South Carolina

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Nursing Research (NINR)

Country where clinical trial is conducted

United States, 

References & Publications (4)

Dose AM. The symptom experience of mucositis, stomatitis, and xerostomia. Semin Oncol Nurs. 1995 Nov;11(4):248-55. Review. — View Citation

Fall-Dickson JM, Ramsay ES, Castro K, Woltz P, Sportés 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 Su — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Pilot Study: Mean Ratings of Oral Mucositis-related Oropharyngeal Pain Intensity on Day 9 (+/- 24 Hours) After Conditioning Chemotherapy (CT)	Subjects rated pain using the Painometer, a hand-held tool with a visual analogue scale to rate overall pain intensity and a list of 14 sensory and 11 affective pain descriptors ranked by intensity values from 1 - 5. Subjects look at the list of sensory and affective words and select words that describe their pain, including Oral Pain and Oral Pain with Swallowing. . The weighted scores assigned to the words are added to obtain a pain intensity score for the sensory and the affective components. The overall pain intensity is measured on a visual analogue scale which has a range of 1 - 10 with high scores indicating higher pain intensity. The sensory and affective pain scores are otained by adding all of the respective intensity values. The range of possible sensory scores is from 0 - 48 and the range of possible affective scores is from 0 - 37. The sensory and affective scores may be added together to obtain the total pain intensity score, which may range from 0 - 85.	Day 9 (+/- 24 hours) after conditioning chemotherapy
Other	Pilot Study: Percentage of Participants Using Word Descriptors of Sensory and Affective Pain Selected by Subjects on Day 9 (+/- 24 Hours) After Conditioning Chemotherapy	Participants selected from 14 word descriptors of sensory (S) pain and 11 word descriptors of affective (A) pain.	day 9 (+/- 24 hours) after conditioning chemotherapy
Primary	What is the Clinical Efficacy of an Etanercept Mouthwash Used for the Treatment of Autologous or Allogeneic Peripheral Blood Stem Cell Transplant or Bone Marrow Transplant Treatment-related Stomatitis?	Clinical efficacy will be determined by measurement of stomatitis grade and oropharyngeal pain.	2 years
Secondary	What is the Toxicity of an Etanercept Mouthwash Used for the Treatment of Autologous or Allogeneic Peripheral Blood Stem Cell Transplant or Bone Marrow Transplant Treatment -Related Stomatitis?	Toxicity will be measured by the incidence of adverse events.	2 years