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| ID | Type | Description | Link |
|---|---|---|---|
| 02-NR-0133 | Other Identifier | NIH CC |
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It was not feasible to recruit required sample size from two clinical sites.
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| Pilot Study | No Intervention | Participants were enrolled in the pilot study to collect descriptive data about pain perception and laboratory techniques. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Etanercept | Drug |
|
| |
| Placebo |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
INCLUSION CRITERIA:
EXCLUSION CRITERIA:
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| Name | Affiliation | Role |
|---|---|---|
| Jane M Fall-Dickson, PhD | National Institute of Nursing Research, National Institutes of Health | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| National Institutes of Health Clinical Center, 9000 Rockville Pike | Bethesda | Maryland | 20892 | United States | ||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 3903598 | Background | 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. | |
| 8348492 | 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. |
| Label | URL |
|---|---|
| NIH Clinical Center Detailed Web Page | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | Main Study Participants | Participants were randomized to one of the following two interventions but the study was not unblinded.
|
| FG001 | Pilot Study | Participants were enrolled in the pilot study to collect descriptive data about pain perception and laboratory techniques. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Main Study Participants | Participants were randomized to one of the following two interventions but the study was not unblinded.
|
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Participants withdrew and analyses were terminated before any data collected. | Posted | 2 years |
|
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Adverse events were not assessed for the pilot study.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Main Study Participants | Participants were randomized to one of the following two interventions but the study was not unblinded.
|
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Suzanne Wingate | NINR/NIH | 301-827-0982 | suzanne.wingate@nih.gov |
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| ID | Term |
|---|---|
| D013280 | Stomatitis |
| D009369 | Neoplasms |
| D007249 | Inflammation |
| ID | Term |
|---|---|
| D009059 | Mouth Diseases |
| D009057 | Stomatognathic Diseases |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D000068800 | Etanercept |
| ID | Term |
|---|---|
| D007141 | Immunoglobulin Fc Fragments |
| D007128 | Immunoglobulin Fragments |
| D010446 | Peptide Fragments |
| D010455 | Peptides |
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| Drug |
|
| 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 | 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 |
| Greenville Cancer Centers of the Carolinas |
| Greenville |
| South Carolina |
| 29615 |
| United States |
| 8578032 | 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. |
| 18164921 | Result | 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. |
| BG001 | Pilot Study | Participants were enrolled in the pilot study to collect descriptive data about pain perception and laboratory techniques. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Number | participants |
|
| Region of Enrollment | Number | participants |
|
| Education | Number | participants |
|
| Cancer Diagnosis | Number | participants |
|
| Cancer stage | Number | participants |
|
| OG001 |
| 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 |
|
| 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. | Posted | Number | event | 2 years |
|
|
|
| Other Pre-specified | 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. | One subject was in critical condition at day 9 after CT, preventing data collection at this time | Posted | Mean | Standard Deviation | units on a scale | Day 9 (+/- 24 hours) after conditioning chemotherapy |
|
|
|
| Other Pre-specified | 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. | One subject was in critical condition at day 9 after CT, preventing data collection at this time | Posted | Number | percentage of participants | day 9 (+/- 24 hours) after conditioning chemotherapy |
|
|
|
| 0 |
| 2 |
| 2 |
| 2 |
| EG001 | Pilot Study | Participants were enrolled in the pilot study to collect descriptive data about pain perception and laboratory techniques. | 0 | 0 | 0 | 0 |
| Fatigue | General disorders | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
|
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| D000602 |
| Amino Acids, Peptides, and Proteins |
| D007127 | Immunoglobulin Constant Regions |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D018124 | Receptors, Tumor Necrosis Factor |
| D018121 | Receptors, Cytokine |
| D011971 | Receptors, Immunologic |
| D011956 | Receptors, Cell Surface |
| D008565 | Membrane Proteins |
| Oral Pain: Pain, affective Dimension |
|
| Oral Pain: Pain, Sensory and affective Dimensions |
|
| Pain with Swallowing: Overall pain intensity |
|
| Pain with Swallowing: Pain, Sensory Dimension |
|
| Pain with Swallowing: Pain, Affective Dimension |
|
| Pain with Swallowing:Sensory & Affective Dimension |
|
| Title | Measurements |
|---|---|
|
| Sensory words: Aching |
|
| Sensory words: Hurting |
|
| Sensory words: Sore |
|
| Sensory words: torturing, splitting, crushing |
|
| S:Cramping, shooting, radiating, stabbing, tearing |
|
| Sensory words: Dull, aching, pressing |
|
| Sensory words: Hurting Group 2 |
|
| Sensory words: Burning, sharp |
|
| Sensory words: Sore Group 2 |
|
| Affective words: Terrifying, torturing |
|
| Affective: Killing, tiring, unbearable, sickening |
|
| A: Nagging, agonizing, troublesome, miserable |
|
| Affective words: Annoying |
|
| Affective words: Torturing |
|
| Affective words: Killing, unbearable, terrifying |
|
| A: Agonizing, troublesome, tiring, sickening |
|
| Affective words: Miserable, nagging |
|
| Affective words: Annoying Group 2 |
|