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

NCT00031551 | Terminated Phase 2 Results DMC

• 2 other identifiers: 02013302-NR-0133
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Stomatitis

Keywords

Stomatitis; Oropharyngeal pain; TNF; Etanercept; Bone marrow transplantation; Chemotherapy; Cancer; Oral cavity; Oral mucous membranes; Randomized controlled clinical trial; Inflammation

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• 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?

  2 years

Other Outcomes (2)

• Pilot Study: Mean Ratings of Oral Mucositis-related Oropharyngeal Pain Intensity on Day 9 (+/- 24 Hours) After Conditioning Chemotherapy (CT)

  Day 9 (+/- 24 hours) after conditioning chemotherapy

• Pilot Study: Percentage of Participants Using Word Descriptors of Sensory and Affective Pain Selected by Subjects on Day 9 (+/- 24 Hours) After Conditioning Chemotherapy

  day 9 (+/- 24 hours) after conditioning chemotherapy

Study Arms (3)

Main Study: Etanercept Mouthwash

EXPERIMENTAL

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.

Drug: Etanercept

Main Study: Placebo Mouthwash

PLACEBO COMPARATOR

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.

Drug: Placebo

Pilot Study

NO INTERVENTION

Participants were enrolled in the pilot study to collect descriptive data about pain perception and laboratory techniques.

Interventions

Etanercept DRUG

Also known as: Enbrel

Main Study: Etanercept Mouthwash

Placebo DRUG

Main Study: Placebo Mouthwash

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Able to understand and sign protocol consent or assent
• Age 16 years or older

You may not qualify if:

• Pregnant or lactating females
• Unable to follow oral rinsing directions
• Intubation
• 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)
• 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
• Known hypersensitivity or allergic reaction to etanercept

Sponsors & Collaborators

• National Institute of Nursing Research (NINR): lead

Study Sites (2)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Greenville Cancer Centers of the Carolinas

Greenville, South Carolina, 29615, United States

Location

Related Publications (4)

• 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.

  PMID: 3903598 BACKGROUND

• 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.

  PMID: 8348492 BACKGROUND

• 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.

  PMID: 8578032 BACKGROUND

• 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.

  PMID: 18164921 RESULT

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Stomatitis; Neoplasms; Inflammation

Interventions

Etanercept

Condition Hierarchy (Ancestors)

Mouth Diseases; Stomatognathic Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Immunoglobulin Fc Fragments; Immunoglobulin Fragments; Peptide Fragments; Peptides; Amino Acids, Peptides, and Proteins; Immunoglobulin Constant Regions; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Receptors, Tumor Necrosis Factor; Receptors, Cytokine; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins

Results Point of Contact

• Title: Suzanne Wingate
• Organization: NINR/NIH

suzanne.wingate@nih.gov

301-827-0982

Study Officials

• Jane M Fall-Dickson, PhD

  National Institute of Nursing Research, National Institutes of Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 7, 2002
• First Posted: March 8, 2002
• Study Start: March 1, 2002
• Primary Completion: August 1, 2010
• Study Completion: August 1, 2010
• Last Updated: December 6, 2017
• Results First Posted: December 30, 2015

Record last verified: 2017-11

Locations

US (2)