This phase I/Ib trial studies the best application time of fenretinide patches and tests how well they work to prevent oral cancer in patients with precancerous lesions in the lining of the mouth (oral intraepithelial neoplasia [OIN]). Oral cancer, which is a devastating and often deadly disease, arises from precancerous lesions in the lining of the mouth. Fenretinide is a synthetic vitamin A derivative which is being studied in the treatment and prevention of some types of cancer. Fenretinide may cause ceramide (a wax-like substance) to build up in tumor cells and kill them. Fenretinide patches are applied to the OIN lesions so fenretinide can be released directly into the lesion. Fenretinide patches may be a safe and effective way to prevent oral cancer in patients with OIN lesions.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT07149220.
PRIMARY OBJECTIVES:
I. Identify the time needed to deliver target level of fenretinide to surface oral epithelium. (Single dose)
II. Lesional histologic grade. (Multi-dose)
III. Lesional clinical size & appearance. (Multi-dose)
IV. Loss of heterozygosity at putative tumor suppressor gene loci associated with OIN progression to oral cavity squamous cell carcinoma (OSCC): 3p14 (FHIT), 9p21(INK4a/ARF), 9p22 (IFN-α), and 17p13 (p53) (FHIT, p53, p16). (Multi-dose)
SECONDARY OBJECTIVES:
I. Evaluate levels of fenretinide in saliva and sera after single patch application. (Single dose)
II. Patient and clinician assessment of patch use and associated side effects. (Single dose)
III. Tissue metabolic profile (CYP3A4 and UGT1A protein expression) and its relation to efficacy (reduction in lesional histologic grade, loss of heterozygosity [LOH], and clinical size). (Multi-dose)
IV. Relation of tissue fenretinide levels to chemopreventive efficacy. (Multi-dose)
V. Determination of pharmacologic advantage (comparison of target tissue fenretinide levels relative to sera). (Multi-dose)
VI. Patient acceptability as measured by patch adherence to target site, ease of patch removal following application time, and residual after taste (sponsor-developed scale). (Multi-dose)
OUTLINE: Participants are assigned to 1 of 2 phases.
SINGLE DOSE PHASE: Participants undergo placement of fenretinide patch to oral mucosa over 15 or 30 minutes during elective extraction of impacted mandibular third molar. Participants also undergo blood and tissue sample collection on study.
MULTI-DOSE PHASE: Patients apply fenretinide patch to OIN lesion over 15 minutes twice daily (BID) for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection and biopsy on study as well as digital imaging throughout the study.
After completion of study treatment, multi-dose phase patients are followed up at days 50 and 85.
Lead OrganizationOhio State University Comprehensive Cancer Center
Principal InvestigatorSusan Regina Mallery
