Intralesional 5-fluorouracil Injection for the Treatment of Oral Leukoplakia

Study Overview
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Brief Summary
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This is a single center, open-label, interventional pilot study to assess the feasibility, safety, and preliminary efficacy of intralesional 5-FU injections for the treatment of oral leukoplakia (OL).

Detailed Description
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PRIMARY OBJECTIVE: I. Evaluate the feasibility of intralesional 5-fluorouracil (5-FU) injection for the treatment of oral leukoplakia SECONDARY OBJECTIVE: I. Evaluate the safety profile and side effects of the study drug. OUTLINE: Participants diagnosed with OL will receive multiple intralesional injections of 5-FU solution over a maximum period of 6 weeks, followed by a follow-up visit after 3 months.

Official Title
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Intralesional 5-fluorouracil Injection for the Treatment of Oral Leukoplakia: a Pilot Study

Conditions
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Oral Leukoplakia

Intervention / Treatment
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* Drug: 5-fluorouracil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults, 18 years of age or older Any gender, race, or ethnicity Clinical diagnosis of oral leukoplakia and biopsy proven dysplasia (any grade) Oral leukoplakia at least 1 cm in largest diameter Ability to understand and willingness to sign a written informed consent document Willingness to provide blood and tissue from diagnostic biopsies Any smoking history is permitted Exclusion Criteria: Pregnant or lactating women Men and women unwilling to use contraception while on study History of malignancy that required cytotoxic chemotherapy within the previous 3 months Use of 5-FU (systemic or topical) within 3 months prior to study enrollment History of allergic reaction or severe hypersensitivity to 5-FU and/or lidocaine Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data

Ages Eligible for Study
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Minimum Age: 18 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: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 5-fluorouracil<br>Participants will receive up to 3 intralesional 5-fluorouracil injections (0.25 mL of a 50mg/mL solution) once every 2 weeks into an oral leukoplakia lesion. | Drug: 5-fluorouracil<br>* Given intralesionally by injection<br>* Other names: 5FU;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants s who complete 5-FU injections | The number of participants who completed the full course of 3 intralesional injections will be compared to the overall total of participants. If the the mucosa becomes ulcerated or participants are unable/unwilling to continue with therapy, 5FU injections will be stopped. | Up to 6 weeks | 
| Number of participants with treatment-related adverse events | The number of participants with documented treatment-related adverse events classified by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be reported | Up to 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in area of clinically visible oral leukoplakia lesions | The total change in area (measured to nearest millimeter (mm) of clinically visible oral leukoplakia lesion will be defined by the product of the two largest perpendicular measurements. The two largest perpendicular measurements of the treated oral leukoplakia lesion will be measured and multiplied to calculate the lesion area at baseline and again at 3 months. | Up to 3 months | 
| Proportion of participants with a change in histologic grade | A board-certified oral and maxillofacial pathologist will review biopsy specimens obtained from the treated oral leukoplakia before and after treatment with 5FU and determine change in histologic grade from baseline. | Up to 3 months | 
| Change in scores on the oral mucosal diseases quality of life questionnaire (COMD-QLQ) | The oral mucosal diseases quality of life questionnaire (COMD-QLQ) is a validated instrument that will assesses the effect that oral leukoplakia has on participants' daily life activities before and after 5-FU intralesional therapy. The survey consists of 24 questions with five response options per item. The response for each item is coded from 0 to 4 with not at all=0 and extremely=4 (at time of scoring, for 3 questions, the Likert scale is reversed). The summary of the overall score ranges from 0 to 104, with a higher score indicating a poorer patient-assessed quality of life score. | Up to 3 months |