Trial Outcomes & Findings for Clinical Evaluation of Bioadhesive Gels for Oral Cancer Chemoprevention (NCT NCT01192204)

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

41 participants

Primary outcome timeframe

Before and after the 3 month treatment.

Results posted on

2015-08-14

Participant Flow

41 patients were enrolled in this protocol. 1 patient could not keep the appointments and was referred to his private oral surgeon.

Participant milestones

Participant milestones
Measure	10% FBR 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	Placebo 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
Overall Study STARTED	23	18
Overall Study COMPLETED	22	18
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	10% FBR 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	Placebo 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
Overall Study could not keep recall appointments	1	0

Baseline Characteristics

Clinical Evaluation of Bioadhesive Gels for Oral Cancer Chemoprevention

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	10% FBR Gel n=23 Participants 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	Placebo Gel n=18 Participants 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 n=41 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	17 Participants n=5 Participants	5 Participants n=7 Participants	22 Participants n=5 Participants
Age, Categorical >=65 years	6 Participants n=5 Participants	13 Participants n=7 Participants	19 Participants n=5 Participants
Age, Continuous	62.2 years STANDARD_DEVIATION 1.8 • n=5 Participants	57.7 years STANDARD_DEVIATION 2.9 • n=7 Participants	59.9 years STANDARD_DEVIATION 2.4 • n=5 Participants
Sex: Female, Male Female	14 Participants n=5 Participants	9 Participants n=7 Participants	23 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	9 Participants n=7 Participants	18 Participants n=5 Participants
Region of Enrollment United States	23 participants n=5 Participants	18 participants n=7 Participants	41 participants n=5 Participants

PRIMARY outcome

Timeframe: Before and after the 3 month treatment.

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

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).

Outcome measures

Outcome measures
Measure	10% FBR Gel n=22 Participants 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	Placebo Gel n=18 Participants 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
Light Microscopic Histologically Scored Diagnoses Pretreatment to Post Treatment Pretreatment	2.36 unit on histologic grade scale Standard Error 0.35	2.83 unit on histologic grade scale Standard Error 0.34
Light Microscopic Histologically Scored Diagnoses Pretreatment to Post Treatment Posttreatment	1.9 unit on histologic grade scale Standard Error 0.21	2.58 unit on histologic grade scale Standard Error 0.17

SECONDARY outcome

Timeframe: pretreatment and posttreatment (3 months treatment duration)

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.

Outcome measures

Outcome measures
Measure	10% FBR Gel n=22 Participants 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	Placebo Gel n=18 Participants 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
Changes in Lesional Sizes	-26.12 mm^2 Standard Deviation 5.81	18.12 mm^2 Standard Deviation 4.39

SECONDARY outcome

Timeframe: Before and after the 3 month treatment duration

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.

Outcome measures

Outcome measures
Measure	10% FBR Gel n=22 Participants 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	Placebo Gel n=18 Participants 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
Treatment Changes in Loss of Heterozygosity Events	0.9 LOH events Standard Error 0.02	0.4 LOH events Standard Error 0.03

Adverse Events

10% FBR Gel

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo Gel

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Susan R, Mallery DDS, PhD

The Ohio State University

Phone: 614 292-5892

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place