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

项目摘要/摘要 据估计，全球每年有40万人被诊断出患有这种疾病，其中包括3万美国人。 口腔鳞癌(OSCC)。在新诊断的口腔癌病例中，约80%位于肿瘤内- 淋巴结转移(TNM)I/II期，无区域淋巴转移或远处转移。为了这些 早期口腔癌患者，五年生存率估计为60%。目前，没有 为40%的早期口腔癌患者提供替代疗法，这些患者具有癌症特异性死亡率的高风险。 由于80%的口腔癌患者在确诊时处于早期阶段，因此有机会 哪些准确的预测和后续的适当治疗决策将显著改善5年 这种致命疾病患者的存活率。 为了解决这些关键的差距，我们建议评估5%咪喹莫特乳膏在新佐剂中的疗效。 环境，机会窗研究，在口腔鳞癌的组织学诊断和最初的 肿瘤外科手术。咪喹莫特是FDA批准的TLR(Toll样受体)激动剂。我们之前已经报道过 口腔内局部应用咪喹莫特导致恶性黑色素瘤完全消退 不良事件最少，患者5年无复发生存。咪喹莫特可诱导肿瘤细胞 促进细胞凋亡和坏死，并激活抗肿瘤免疫反应。 在目前的建议中，我们的目标是进行概念验证研究(探索性临床试验)，以评估 新辅助免疫调节剂咪喹莫特局部治疗对缩小初发口腔大小的作用 并评估其在早期口腔癌患者中的安全性和毒性(目标1)。在目标2中，我们将评估 定量多重免疫荧光法研究咪喹莫特的抗肿瘤和免疫调节作用。 这一发现将提供提高早期口腔鳞癌总体存活率的强化治疗方案 病人。

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.