Fenretinide Mucoadhesive Patch: Evaluation of Oral Cancer Prevention Efficacy in Adults With Premalignant Oral Lesions.

NCT07149220 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: SMFMS-001.2025R01CA227273
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Oral Leukoplakia; Oral Dysplasia

Keywords

oral cancer prevention

Outcome Measures

Primary Outcomes (3)

• Histopathologic grade (assessed using light microscopy)

  Complementary outcome measures of the Multi-dose Chemoprevention Evaluation in Subjects with OIN described separately. To evaluate both intra-participant (pretreatment and post treatment parameters) and collective assessments (all pretreatment findings relative to all post treatment findings) of the following chemoprevention indicators: Pretreatment and posttreatment lesional histologic grade, which will be determined by a ABOMP certified pathologist using light microscopy.

  The time frame is 12 months for participant recruitment and completion of the six week clinical trial.

• Clinical size (determined by measurement with a flexible ruler)

  Clinical images including internal measurement device (flexible ruler) to be taken prior to biopsy, and weekly at every monitoring visit.

  The time frame is 12 months for participant recruitment and completion of the six week clinical trial.

• Loss of heterozygosity (measured by genomic analyses

  Loss of heterozygosity indices at tumor suppressor gene loci associated with progression of OIN lesions to OSCC \[3p14 (FHIT), 9p21 (INK4a/ARF), 9p22 (IFN-α), and 17p13 (p53)\] (FHIT, p53, p16)\] will be evaluated in DNA isolated from lesional epithelium.

  The time frame is 12 months for participant recruitment and completion of the six week clinical trial.

Secondary Outcomes (2)

• CYP4A4 and UGT1A1 enzyme levels (measured by image analysis quantified immunohistochemistry)

  The time frame is 12 months for participant recruitment and completion of the six week clinical trial.

• fenretinide patch acceptance (measured by validated assessment tool completed by patients)

  The time frame is 12 months for participant recruitment and completion of the six week clinical trial.

Study Arms (1)

FMS impact on premalignant oral epithelial lesions

EXPERIMENTAL

Evaluation of the impact of the fenretinide-releasing system on premalignant oral epithelial lesions

Drug: Mucoadhesive fenretinide-releasing system (FMS)

Interventions

Mucoadhesive fenretinide-releasing system (FMS) DRUG

All persons with premalignant oral epithelial lesions will receive active intervention. The intervention consists of b.i.d. application of the FMS to the premalignant lesion for a total of six weeks. Please note that the intervention title Drug and intervention titled Other are the same entity.

FMS impact on premalignant oral epithelial lesions

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Previous history of OSCC.
• Microscopic diagnosis of OSCC or carcinoma in situ at the pretreatment biopsy.
• Undergoing cancer treatments except for basal cell carcinoma of the skin.
• Inability to stop tobacco product use.
• Incapable of providing informed consent.
• Pregnancy or unwilling to comply with birth control and monthly pregnancy testing criteria.

Sponsors & Collaborators

• Ohio State University: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Ohio State University College of Dentistry

Columbus, Ohio, 43210, United States

RECRUITING

Related Publications (4)

• Desai KG, Mallery SR, Holpuch AS, Schwendeman SP. Development and in vitro-in vivo evaluation of fenretinide-loaded oral mucoadhesive patches for site-specific chemoprevention of oral cancer. Pharm Res. 2011 Oct;28(10):2599-609. doi: 10.1007/s11095-011-0489-3. Epub 2011 Jun 15.

  PMID: 21674264 BACKGROUND

• Wu X, Desai KG, Mallery SR, Holpuch AS, Phelps MP, Schwendeman SP. Mucoadhesive fenretinide patches for site-specific chemoprevention of oral cancer: enhancement of oral mucosal permeation of fenretinide by coincorporation of propylene glycol and menthol. Mol Pharm. 2012 Apr 2;9(4):937-45. doi: 10.1021/mp200655k. Epub 2012 Mar 6.

  PMID: 22280430 BACKGROUND

• Holpuch AS, Phelps MP, Desai KG, Chen W, Koutras GM, Han BB, Warner BM, Pei P, Seghi GA, Tong M, Border MB, Fields HW, Stoner GD, Larsen PE, Liu Z, Schwendeman SP, Mallery SR. Evaluation of a mucoadhesive fenretinide patch for local intraoral delivery: a strategy to reintroduce fenretinide for oral cancer chemoprevention. Carcinogenesis. 2012 May;33(5):1098-105. doi: 10.1093/carcin/bgs122. Epub 2012 Mar 15.

  PMID: 22427354 BACKGROUND

• Wang D, Pei P, Shea F, Spinney R, Chang A, Lahann J, Mallery SR. Growth modulatory effects of fenretinide encompass keratinocyte terminal differentiation: a favorable outcome for oral squamous cell carcinoma chemoprevention. Carcinogenesis. 2024 Jun 10;45(6):436-449. doi: 10.1093/carcin/bgae022.

  PMID: 38470060 BACKGROUND

Related Links

• URL for Desai et al. publication
• URL for the Holpuch et al. publication
• URL for the Wu et al. publication

MeSH Terms

Conditions

Leukoplakia, Oral

Condition Hierarchy (Ancestors)

Mouth Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Neoplasms; Leukoplakia; Precancerous Conditions; Mouth Diseases; Stomatognathic Diseases; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Study Officials

• Susan R. Mallery, DDS, PhD

  Ohio State University College of Dentistry

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Susan R. Mallery, DDS, PhD

CONTACT

614-292-6577; mallery.1@osu.edu

Daren Wang, DDS, PhD

CONTACT

614-292-6577; Wang.7277@osu.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: The research scientist who will be conducting the LOH analyses will be blinded as to whether the sample is pre or post treatment.
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Chair

Model Details: All participants with premalignant oral epithelial lesions will receive the active, fenretinide-releasing mucoadhesive system. There is no placebo control for this early Phase Ib study.

Study Record Dates

• First Submitted: August 18, 2025
• First Posted: August 29, 2025
• Study Start: September 1, 2025
• Primary Completion (Estimated): June 2, 2026
• Study Completion (Estimated): August 30, 2026
• Last Updated: August 29, 2025

Record last verified: 2025-08

Locations

US (1)