Clinical Evaluation of Bioadhesive Gels for Oral Cancer Chemoprevention

Study Overview
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Brief Summary
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This is a multicenter placebo-controlled clinical trial to assess the effects of a topically applied gel on precancerous oral epithelial lesions. A total of 41 participants will be enrolled in this trial, and 22 of them will be enrolled at Ohio State. [The remaining 19 participants will be enrolled at the University of North Carolina (9 participants) and the University of Louisville (8 participants)]. At all three institutions, half of the participants will randomly be assigned to the 10% FBR gel (0.5 gm four times daily for 3 months), while half will enter the placebo control arm. All trial participants will have a pretreatment (including lesional and perilesional tissue) biopsy taken before and an excisional biopsy after 3 months of treatment. As pretreatment indices are compared to post treatment effects on each patient, patients serve as their own internal control. Pretreatment lesional biopsies are obtained to establish a pretreatment diagnosis and provide a pretreatment baseline for the experimental parameters.

Detailed Description
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Forty one (41) patients with microscopically confirmed premalignant oral epithelial disease (epithelial dysplasia) will be enrolled in this trial at three clinical centers, i.e. the Ohio State University, University of North Carolina at Chapel Hill and University of Louisville. At all three institutions, half of the participants will randomly be assigned to the 10% FBR gel (0.5 gm four times daily for 3 months), while half will enter the placebo control arm. In accordance with the established standard of care, all participants need to have biopsies taken of their suspicious oral lesions to establish the diagnosis (non research). Trial participants will have three total biopsies. Pretreatment biopsies will entail: 1) perilesional tissue and single saliva sample for FBR metabolic profiling studies (tissue and saliva will be obtained 15 minutes after a single 0.5 gm application of 10% FBR gel for metabolic profiling. Gel application and nonlesional biopsy will be obtained before incisional biopsy of lesional tissue), and 2) a hemisection of lesional tissue to establish a diagnosis and provide a pretreatment baseline for the experimental parameters. While the pretreatment biopsy includes removal of both perilesional and lesional tissue, there will only be one surgical wound as the perilesional tissue is contiguous with the lesional tissue. A final excisional biopsy of the treatment site including any remaining residual lesional tissue (excision of oral dysplastic lesions is consistent with current standards of care) will be obtained after 3 months of treatment. The experimental design permits each patient to serve as their own internal control. Briefly, these following parameters will be monitored in all participants (comparisons made relative to patient-matched pretreatment to posttreatment biopsies): 1) light microscopic diagnoses, 2) clinical appearances and lesional sizes, 3) microarray gene expression analyses, 4) microvascular densities of superficial connective tissues, 5) LOH indices at loci associated with tumor suppressor genes, 6) intraepithelial levels of COX-2 and iNOS protein (image analysis quantified immunohistochemistry), 7) comparison of FBR metabolic profiles relative to extent of chemopreventive efficacy noted.

Official Title
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Clinical Evaluation of Bioadhesive Gels for Oral Cancer Chemoprevention

Conditions
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Squamous Cell Carcinoma of Mouth, Intraepithelial Neoplasia

Intervention / Treatment
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* Drug: 10% FBR containing bioadhesive gel
* Drug: placebo gel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ages: 21 to 80 Microscopically confirmed premalignant oral epithelial disease No previous history of cancer (with the exception of basal cell carcinoma of the skin) Tobacco free for at least six weeks prior to entrance in the trial and remain tobacco-free for the three month duration of the study Availability for necessary study follow-up evaluations (every 10 to 14 days during the trial) Capable of providing informed consent. Exclusion Criteria: Previous history of cancer (with the exception of basal cell carcinoma of the skin) Current use of tobacco products or refusal to remain tobacco-free for the three month duration of the study Lack of microscopically confirmed premalignant oral epithelial changes Microscopic diagnosis of oral squamous cell carcinoma Previous history of radiation therapy on same side of the head and neck region History of allergy to any kind of berry Women who are determined to be pregnant or plan to be pregnant during the trial Women who are nursing.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 10% FBR containing bioadhesive gel<br>Drug consisting of 10% FBR containing bioadhesive gel. Participants instructed to apply 0.5 gm of 10% FBR containing bioadhesive gel four times a day to lesional site | Drug: 10% FBR containing bioadhesive gel<br>* 0.5 gm applied 4 times daily to the oral premalignant lesion site for a duration of 3 months<br>* Other names: BRB gel;|
| Placebo Comparator: Placebo Gel<br>Color/consistency matched placebo (no black raspberry) gel | Drug: placebo gel<br>* 0.5 gm applied 4 times daily to the oral premalignant lesion site for a duration of 3 months<br>* Other names: BRB devoid placebo gel;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Light Microscopic Histologically Scored Diagnoses Pretreatment to Post Treatment | A hemisection of lesional tissue will be conducted before the 3 month treatment to establish a diagnosis and provide a pretreatment baseline for the experimental parameters. Anl excisional biopsy of the treatment site including any remaining residual lesional tissue (excision of oral dysplastic lesions is consistent with current standards of care) will be obtained after 3 months of treatment to provide a posttreatment diagnosis. The 0 to 8 histologic scale was:0=normal with or without hyperkeratosis BEST OUTCOME, 1=atypia, 2=mild dysplasia, 3=mild-moderate dysplasia, 4=moderate dysplasia,5=moderate-severe dysplasia,6=severe dysplasia, 7=carcinoma in situ, 8=invasive oral squamous cell carcinoma (WORST OUTCOME). | Before and after the 3 month treatment. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Lesional Sizes | The remaining oral dysplasia lesion will be inspected at each follow up appointment (every 10-14 days). Biopsies will be immediately conducted on patients with any indication of malignant transformation including indurated, rolled borders, nonhealing ulcers, etc. Accordingly, these patients will withdraw from the trial. Participants will also be monitored for any changes consistent with contact mucositis e.g. soreness and erythema at application site. Clinical photographs were taken for the patients records. Pre treatment and post treatment photographs, with a ruler in place, were used for accurate pre and post treatment size measurement. NOTE: if treatment is beneficial, lesional size will decrease which will be reflected as a negative number. | pretreatment and posttreatment (3 months treatment duration) | 
| Treatment Changes in Loss of Heterozygosity Events | Laboratory experiments will be conducted to assess the effects of gel treatment on pre and post loss of heterozygosity (LOH) events at loci associated with tumor suppressor genes. | Before and after the 3 month treatment duration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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FBR, OSCC, chemoprevention