Neoplasms

All Conditions

Mouth and Tooth Diseases

Rare Diseases

Carcinoma

Carcinoma, Squamous Cell

Mouth Neoplasms

Head and Neck Neoplasms

Mouth Diseases

Stomatognathic Diseases

Oral Squamous Cell Carcinoma

Oral Cancer

Lip and Oral Cavity Cancer

Herbal and Botanical

All Drugs and Chemicals

Raspberry

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

Color/consistency matched placebo (no black raspberry) gel

0.5 gm applied 4 times daily to the oral premalignant lesion site for a duration of 3 months

10% FBR containing bioadhesive gel

placebo gel

Susan R Mallery, DDS, PhD

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.

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.

Clinical Evaluation of Bioadhesive Gels for Oral Cancer Chemoprevention

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).

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.

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.

University of Louisville

University of North Carolina, Chapel Hill

National Cancer Institute (NCI)

Ohio State University

Professor

Active 10% FBR containing bioadhesive gel

Bioadhesive 10% freeze-dried black raspberry gel: 0.5 gm applied 4 times daily to the oral premalignant lesion site for a duration of 3 months

No adverse events

10% FBR Gel

Color/consistency matched placebo (no black raspberry) gel

Color/consistency matched placebo gel: 0.5 gm applied 4 times daily to the oral premalignant lesion site for a duration of 3 months

No adverse events

Placebo Gel

Active 10% FBR containing bioadhesive gel

Bioadhesive 10% freeze-dried black raspberry gel: 0.5 gm applied 4 times daily to the oral premalignant lesion site for a duration of 3 months

Color/consistency matched placebo (no black raspberry) gel

Color/consistency matched placebo gel: 0.5 gm applied 4 times daily to the oral premalignant lesion site for a duration of 3 months

Total

The patients were randomly assigned by computer generated numbers to either the BRB or the placebo gel groups.

Age, Categorical

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

While we initially planned to include microvascular densities and COX-2 analyses, there were insufficient tissue samples to collect these data. Therefore as we do not have these data we can not report them.

Susan R, Mallery DDS, PhD

Wilcoxon matched-pairs signed rank test (intrapatient pre versus post treatment scores)

Wilcoxon matched-pairs signed rank test (pre versus post treatment scores)

Pretreatment

Posttreatment

The population evaluated were as previously described i.e. 22 participants in the BRB gel cohort and 18 participants in the placebo gel cohort.

Light Microscopic Histologically Scored Diagnoses Pretreatment to Post Treatment

Active 10% FBR containing bioadhesive gel

Bioadhesive 10% freeze-dried black raspberry gel: 0.5 gm applied 4 times daily to the oral premalignant lesion site for a duration of 3 months.

Changes in Lesional Sizes

Treatment Changes in Loss of Heterozygosity Events

Overall Study

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

laboratory biomarker analysis

lyophilized black raspberries(LBR) administration: 3 LBR troche lozenges (dissolved in mouth), 4 times/day beginning at minimum of 24 hrs following biopsy until night before surgery

preventative dietary intervention

Amit Agrawal

This pilot phase I trial studies freeze-dried black raspberries in treating patients with oral squamous cell cancer undergoing surgery. Chemoprevention is the use of certain drugs to keep cancer from forming. Eating freeze-dried black raspberries may help prevent or treat oral cancer

PRIMARY OBJECTIVES:

I. To determine the relationship between the length of short-term lyophilized black raspberries (LBR) administration to human oral cancer patients and the modulation, in oral cavity tissues, of a subset of specific genes previously identified by us to be "LBR-responsive" and associated with LBR's chemopreventive activity.

SECONDARY OBJECTIVES:

I. To evaluate the effects of LBR administration in humans on cell proliferation, apoptosis, and angiogenesis in oral cavity tissues using various established biomarkers including Ki-67 or proliferating cell nuclear antigen (PCNA), caspase-3, vascular endothelial growth factor (VEGF) or basic fibroblast growth factor (bFGF).

II. To assess the feasibility of administering lyophilized freeze-dried black raspberries in oral troche form to pre-surgical patients diagnosed with squamous cell carcinoma of the oral cavity (compliance, tolerance, adverse events).

Freeze-Dried Black Raspberries in Treating Patients With Oral Squamous Cell Cancer Undergoing Surgery

A Phase 1b Pilot Study Evaluating Oral Administration of Freeze-Dried Black Raspberries in Pre-Surgical Patients With Oral Squamous Cell Carcinoma

Statistical summaries of biopsy to surgery changes in quantitative real-time RT-PCR data made on the log scale (geometric mean of percent changes +/- s.e. expressed as a percentage).Confidence intervals produced and significance of the correlation between real-time RT-PCR values and period of treatment (i.e. time from biopsy to surgery) using Fisher's transformation of Spearman's rank correlation tested. Semi-quantitative IHC analyzed using an ordinal logistic model to determine significance of associations between period of treatment and change in staining from biopsy to surgery.

Biomarkers include Ki-67, PCNA, caspase-3, VEGF, or bFGF

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Clinical Evaluation of Bioadhesive Gels for Oral Cancer Chemoprevention	NCT01192204	Squamous Cell C... Intraepithelial...	10% FBR contain... placebo gel	21 Years - 80 Years	Ohio State University
Clinical Evaluation of Bioadhesive Gels for Oral Cancer Chemoprevention	NCT01192204	Squamous Cell C... Intraepithelial...	10% FBR contain... placebo gel	21 Years - 80 Years	Ohio State University
Clinical Evaluation of Bioadhesive Gels for Oral Cancer Chemoprevention	NCT01192204	Squamous Cell C... Intraepithelial...	10% FBR contain... placebo gel	21 Years - 80 Years	Ohio State University
Freeze-Dried Black Raspberries in Treating Patients With Oral Squamous Cell Cancer Undergoing Surgery	NCT01465776	Squamous Cell C...	laboratory biom... preventative di...	18 Years -	Ohio State University Comprehensive Cancer Center
Clinical Evaluation of Bioadhesive Gels for Oral Cancer Chemoprevention	NCT01192204	Squamous Cell C... Intraepithelial...	10% FBR contain... placebo gel	21 Years - 80 Years	Ohio State University

Spots Global Cancer Trial Database for squamous cell carcinoma of mouth