Safety and Chemopreventive Efficacy of Fenretinide Mucoadhesive System in Subjects With Premalignant Oral Intraepithelial Neoplasia (OIN) Lesions: In Conjunction With Pharmacokinetic Assessment in Healthy Subjects.
The goal of this clinical trial is to determine the effect of a mucoadhesive system that releases the vitamin A derivative, fenretinide (FMS), on precancerous surface epithelial (lining tissue inside your mouth) changes. Specifically, does application of the FMS induce specific changes: 1) reduction in the clinical size, 2) reduction in the histologic grade of precancerous changes (determined by microscopic examination), 3) reduce the nuclear LOH events (changes in copy number of key genes to prevent oral cancer). The first part of this study entails a single FMS application to persons having their wisdom teeth removed. This study is done to confirm how long the FMS needs to remain in place to release the cancer-preventive agent. Participants will: 1) Have the FMS applied over the impacted wisdom tooth for 15 minutes, 2) FMS is removed, saliva is collected, and blood is drawn from a vein in the arm. 3) Tissue overlying the impacted wisdom tooth is removed and analyzed. The second, multi-FMS application entails patients who have precancerous oral surface epithelial changes. These patients will have: 1) a piece of the precancerous tissue removed (biopsy) and examined under a microscope to ensure the diagnosis. Blood is drawn from a vein in the arm., 2) One week after the biopsy, return to discuss the results. If the changes are precancerous, this person will be given FMS to apply to the site twice a day. 3) Patients return every 7 to 10 days (for a total of six weeks) for an oral exam and clinical pictures, return the FMS, and obtain new FMS for the upcoming week., 4) At week 3 (midway), blood is drawn from a vein in the arm., 5) After the six weeks of treatment, clinical pictures are obtained, blood is drawn from a vein in the arm and all of the remaining treated tissue is completely removed. The patient is securely contacted and results are discussed. 6) Approximately 6 weeks after the final surgery, patients return for a complete oral examination and clinical pictures are obtained.
⁃ Adults, 18 years or older, with microscopically confirmed OIN. Only one clinically measurable OIN lesion (\> 3x3 mm) and capable of full coverage by the FMS with a small zone of extension (2.1 x 2.1 cm smaller FMS, 2.8 x 2.8 larger FMS) will be evaluated in this study. If multiple suspicious lesions are noted, the most clinically advanced lesion will be selected for treatment. The patient will be provided the option to have the other lesions biopsied (self-pay and/or insurance) at another appointment or to schedule with another provider for management.
• No use of tobacco products 6 weeks prior to and during the 6-week study. (confirmed via random cotinine saliva tests for former tobacco users).
• Available for follow-up evaluations (every 7-10 days during trial), amenable to full 6-week study participation, and 6-week post-study recall.
• All men and reproductive aged women of child bearing potential must agree to use contraception during treatment and 1 month after end of treatment. All reproductive aged, heterosexually active women must undergo monthly pregnancy testing.
• Capable of providing informed consent.