Exploratory clinical trial of topical Imiquimod 5% cream as window-of-opportunity monotherapy for early-stage oral cancer

PROJECT SUMMARY / ABSTRACT Each year an estimated 400,000 people globally, among them 30,000 Americans, are newly diagnosed with oral squamous cell carcinoma (OSCC). Of the newly diagnosed oral cancer cases, ~80% are in the tumor- node-metastasis (TNM) Stage I/II without regional lymph node involvement or distant metastasis. For these early-stage oral cancer patients, the five-year survival rate is estimated to be 60%. Currently, there is no alternative therapy for 40% of early-stage oral cancer patients at high risk for cancer-specific mortality. As 80% of oral cancer patients are in early stage at the time of diagnosis, a window of opportunity exists in which accurate prognostication and subsequent decisions for proper treatment will dramatically improve 5-year survival of patients with this deadly disease. To address these critical gaps, we propose to assess efficacy of topical imiquimod 5% cream in a neoadjuvant setting, a window-of-opportunity study, administered between the histologic diagnosis of OSCC and the initial surgery of tumor. Imiquimod is an FDA-approved TLR (Toll-like receptor) agonist. We have previously reported that intra-oral application of topical imiquimod resulted in complete resolution of malignant melanoma with minimal adverse events and the patient had recurrence-free 5-year survival. Imiquimod can induce tumor cell apoptosis and necrosis, and activate anti-tumoral immune response. In the current proposal, we aim to conduct a proof-of-concept study (exploratory clinical trial) to assess the efficacy of neoadjuvant imiquimod immunomodulatory topical therapy in reducing the size of primary oral cancer and evaluate its safety and toxicity in early-stage oral cancer patients (Aim 1). In Aim 2, we will evaluate the anti-tumoral and immunomodulatory effects of imiquimod using quantitative multiplex immunofluorescence. The findings will provide enhanced treatment regimen that increase overall survival rate of early-stage OSCC patients.