Non-Invasive Imaging of Oral Cavity Cancer

口腔癌的无创成像

• 批准号: 10472033
• 负责人: Christian Brand
• 金额: $ 74.88万
• 依托单位: SUMMIT BIOMEDICAL IMAGING, LLC
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10472033
• 关键词: Address; Animals; Appointment; Area; Benign; Biological Markers; Biopsy; Blinded; Carcinoma in Situ; Chemistry; Clinical; Clinical Data; DNA Repair Enzymes; Data; Detection; Diagnosis; Diagnostic Imaging; Disease; Distant Metastasis; Drops; Drug Formulations; Dysplasia; Early Diagnosis; Economics; Epithelial; Erythroplasia; Feasibility Studies; Fluorescence; Formulation; Foundations; Friction; Goals; Gold; Heterogeneity; High grade dysplasia; Histologic; Histopathology; Human; Human Resources; Image; Image Analysis; Incidence; Infrastructure; Intuition; Keratosis; Lesion; Leukoplakia; Localized Disease; Location; Malignant - descriptor; Malignant Neoplasms; Medical Imaging; Memorial Sloan-Kettering Cancer Center; Methods; Monitor; Mucous Membrane; Mus; Netherlands; Normal tissue morphology; Oral Pathology; Oral cavity; Organic solvent product; Outcome; Participant; Pathology; Patients; Performance; Pharmaceutical Preparations; Pharmacists; Phase; Phase I Clinical Trials; Phase II Clinical Trials; Phase III Clinical Trials; Population; Predictive Value; Preparation; Production; Public Health; Reader; Reporting; Residual Tumors; Sensitivity and Specificity; Solid; Specificity; Squamous cell carcinoma; Surgical margins; Surveys; Survival Rate; Taste Perception; Technology; Temperature; Testing; Time; Tobacco use; Topical agent; Topical application; Training; Tumor Tissue; Tumor stage; Update; Visit; Visual; Water; base; clinical practice; data registry; efficacy validation; first-in-human; fluorescence imaging; follow-up; human data; imaging agent; imaging platform; improved; in vivo imaging; interest; intravenous injection; lymph nodes; malignant mouth neoplasm; malignant oropharynx neoplasm; negative affect; neoplasm registry; non-invasive imaging; oral lesion; overexpression; phase 1 study; phase I trial; phase II trial; process optimization; recruit; safety study; small molecule; spectrograph; standard of care; surgery outcome; targeted agent; time interval; trend; tumor; uptake

Project Summary/Abstract Counterintuitively, the incidence and societal impact of oral and oropharyngeal cancer are increasing in the US despite the markedly decreased use of tobacco products. This trend is exacerbated by the fact that almost two- thirds of patients have lymph node or distant metastases at the time of diagnosis, dramatically reducing 5-year survival rates. Oral cavity cancers are overwhelmingly diagnosed late despite their superficial location, often because they remain asymptotic – and early lesions are erroneously considered benign. The current standard of care for detecting oral cancer is still visual examination in combination with biopsy-based histopathology, which is not only labor-intensive but also requires highly trained personnel and a sophisticated infrastructure – impenetrable economic barriers for most of the world’s population, and precisely the unmet clinical need we have chosen to address. We recently reported very encouraging first-in-human Phase I clinical trial data with PARPi-FL, a small molecule with high specificity for PARP1. PARP1 is a quantitative and highly overexpressed biomarker for in vivo imaging of oral cancer, and we showed that PARPi-FL identifies tumors with sensitivities and specificities >95%. Taking our drug to the next level and validating its clinical value in a Phase II trial, we have partnered with Memorial Sloan Kettering Cancer Center (MSK) and assembled three Specific Aims (SAs). In SA1, we will redesign the formulation and manufacturing of PARPi-FL, making it easier to formulate for the clinicians as well as improving the taste of the gargling solution for the patient. In SA2, we will optimize workflows, thresholding and image analysis, based on and informed by our Phase I clinical data. In SA3, we will test intraoperative PARPi-FL imaging of the oral cavity to determine sensitivity and specificity in discriminating benign and malignant lesions. If successfully, this project will provide a solid foundation for a multicenter Phase III clinical trial and ultimately raise the clinical standard of care for oral cavity cancer.

项目概要/摘要 与直觉相反的是，美国口腔癌和口咽癌的发病率和社会影响正在增加 尽管烟草制品的使用明显减少，但这一趋势因几乎两成的事实而加剧。 三分之一的患者在诊断时已有淋巴结或远处转移，从而大大缩短了 5 年生存期 尽管口腔癌位于浅表，但绝大多数的存活率都已被诊断为晚期。 因为它们仍然是渐近的——并且早期病变被错误地认为是良性的。 检测口腔癌的护理方法仍然是目视检查与基于活检的组织病理学相结合， 这不仅是劳动密集型的，而且需要训练有素的人员和先进的基础设施—— 对世界上大多数人来说难以逾越的经济障碍，以及我们未得到满足的临床需求 选择解决。 我们最近报告了非常令人鼓舞的小分子 PARPi-FL 的首次人体 I 期临床试验数据 PARP1 具有高特异性，是一种用于体内成像的定量且高度过表达的生物标志物。 口腔癌，我们表明 PARPi-FL 肿瘤的敏感性和特异性 >95%。 我们与以下公司合作，将我们的药物提升到一个新的水平并在 II 期试验中验证其临床价值 纪念斯隆凯特琳癌症中心 (MSK) 并在 SA1 中制定了三个具体目标 (SA)。 重新设计 PARPi-FL 的配方和制造，使冠军配方也更容易 为了改善患者漱口液的味道，在 SA2 中，我们将优化工作流程、阈值。 和图像分析，基于我们的 I 期临床数据并提供信息。在 SA3 中，我们将进行术中测试。 口腔 PARPi-FL 成像以确定区分良恶性的敏感性和特异性 病变。 如果成功，该项目将为多中心III期临床试验并最终提供坚实的基础 提高口腔癌的临床护理水平。