Clinical Evaluation of Bioadhesive Gels for Oral Cancer Chemoprevention

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.

Inclusion Criteria:

1. Ages: 21 to 80

2. Microscopically confirmed premalignant oral epithelial disease

3. No previous history of cancer (with the exception of basal cell carcinoma of the
skin)

4. 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

5. Availability for necessary study follow-up evaluations (every 10 to 14 days during
the trial)

6. Capable of providing informed consent.

Exclusion Criteria:

1. Previous history of cancer (with the exception of basal cell carcinoma of the skin)

2. Current use of tobacco products or refusal to remain tobacco-free for the three month
duration of the study

3. Lack of microscopically confirmed premalignant oral epithelial changes

4. Microscopic diagnosis of oral squamous cell carcinoma

5. Previous history of radiation therapy on same side of the head and neck region

6. History of allergy to any kind of berry

7. Women who are determined to be pregnant or plan to be pregnant during the trial

8. Women who are nursing.