Molecular Characterization Trial

分子表征试验

• 批准号: 10526302
• 负责人: OMAR MIAN
• 金额: $ 24.48万
• 依托单位: CLEVELAND CLINIC LERNER COM-CWRU
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-14 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10526302
• 关键词: Address; Adjuvant; Antibody-drug conjugates; Antineoplastic Agents; Biological; Bladder; Blood; Cancer Patient; Cisplatin; Clinical; Clinical Data; Cohort Studies; Collection; Combined Modality Therapy; Cytotoxic agent; Data; Disease; Foundations; Genetic; Genomics; Goals; Head and Neck Squamous Cell Carcinoma; Hybrids; Image; Immune; Immunologics; Immunotherapy; Intensity-Modulated Radiotherapy; Knowledge; Laboratories; Malignant Neoplasms; Malignant neoplasm of urinary bladder; Modality; Molecular; Nivolumab; Pathogenesis; Patients; Radiation; Radiation Oncology; Radiation therapy; Radiobiology; Recurrence; Research; Research Personnel; Resistance; Sampling; Site; Specimen; Statistical Methods; Surveys; Testing; Therapeutic; Time; Tissues; Treatment Efficacy; anti-PD-1; antitumor effect; base; cancer type; chemoradiation; cohort; data acquisition; design; immune checkpoint blockade; immunomodulatory therapies; immunoregulation; improved outcome; insight; irradiation; multimodal data; muscle invasive bladder cancer; next generation; phase II trial; precision medicine; preservation; radiation effect; radiation resistance; response; sample collection; standard of care; targeted agent; treatment response; trial design; tumor

PROJECT SUMMARY Molecular Characterization Trial Navigating Extended Specimen Surveys for Therapeutic Selection (ROBIN-NESSTS) Summary: Approximately half of all cancer patients are treated with radiation in the course of their disease. There exists an opportunity and urgent need to apply new biological knowledge in the optimization of radiation treatment and its combination with emerging targeted anti-neoplastic agents. At the core of the CCF/Emory ROBIN U54 Center is a branched Molecular Characterization Trial (MCT) focused on longitudinal collection of biospecimens and multimodal data from patients with muscle invasive bladder cancer (MIBC) and head and neck squamous cell carcinoma (HNSCC) prior to-, during, and after radiotherapy. These molecular characterization cohorts have been designed to incorporate immunomodulatory combination therapies as well as standard-of-care chemoradiotherapy, aiming to address pressing translational questions by integrating these trials throughout the ROBIN Center’s cores and projects. These are immune radiobiology-centered “small N, high-content” study cohorts that will allow us to address critical knowledge gaps related to the biological basis responses to combined modality radiotherapy. The central hypothesis being tested is that the longitudinal collection of clinically annotated biospecimens and multimodal data from patients treated prior to, during, and after radiotherapy from MCT cohorts examining radiation-based immunotherapies and standard of care chemoradiation will provide new insights into the genetic, immunologic, and evolutionary basis of therapeutic response. The ability to interrogate key questions across two distinct cancers will amplify our capacity to identify generalizable molecular mechanisms underlying radiation resistance and immunomodulatory activity. Our Specific Aims are to conduct a specimen collection and characterization trial with 2 cohorts: (1) (MCTa): Adaptive RADiation therapy with concurrent Sacituzumab Govitecan (RAD-SG) for bladder preservation in patients with MIBC and (2) a Phase II trial of IMRT re-irradiation plus concurrent and adjuvant nivolumab. The same sample and data acquisition will be obtained from two parallel cohorts of standard of care cisplatin plus RT treated patients (n=20 for each site). The overarching objective of the high- content study cohorts in this MCT is to rigorously dissect common mechanisms and drivers of efficacy and resistance to the most promising radiation-based combinations in two cancers. We will address knowledge gaps related to the genetic, immunologic, and molecular evolutionary basis of response to immunomodulatory combination therapies by seamlessly integrating multi-modal data from these clinical cohorts across the ROBIN Center’s laboratories, projects, and cores.

项目摘要 分子表征试验 导航用于治疗选择的扩展标本调查（ROBIN-NESSTS） 摘要：大约一半的癌症患者在疾病过程中接受放射治疗。 在辐射优化中应用新的生物学知识存在着机遇和迫切的需求 治疗及其与新兴的靶向抗肿瘤剂的组合。CCF/Emory的核心 ROBIN U54中心是一个分支的分子表征试验（MCT），专注于纵向收集 来自肌层浸润性膀胱癌（MIBC）和头部的患者的生物标本和多模式数据， 颈部鳞状细胞癌（HNSCC）放疗前、放疗中和放疗后。这些分子 特征化队列也被设计为结合免疫调节联合治疗 作为标准化放疗，旨在通过整合 这些试验贯穿罗宾中心的核心和项目。这些是以免疫放射生物学为中心的 “小N，高内容”的研究队列，这将使我们能够解决关键的知识差距， 生物学基础对联合放疗的反应。正在测试的中心假设是， 纵向收集临床注释的生物样本和来自之前治疗的患者的多模态数据， 在MCT队列的放疗期间和放疗后，检查基于放射的免疫疗法和 治疗放化疗将提供新的见解，遗传，免疫学和进化的基础， 治疗反应。在两种不同的癌症中询问关键问题的能力将放大我们的 确定辐射抗性的普遍分子机制的能力， 免疫调节活性。我们的具体目标是进行标本采集和表征试验 2个队列：（1）（MCTa）：适应性放射治疗与Sacituzumab Govitecan（RAD-SG）同时治疗 MIBC患者的膀胱保存和（2）IMRT再照射加同时和 佐剂纳武单抗。将从两个平行队列中获得相同的样本和数据采集。 标准护理顺铂加RT治疗的患者（每个部位n = 20）。高级别会议的总体目标是： 本MCT中的内容研究队列旨在严格剖析疗效的常见机制和驱动因素， 对两种癌症中最有希望的基于辐射的组合的抗性。我们将讨论知识 与免疫调节反应的遗传、免疫学和分子进化基础相关的缺口 通过无缝整合来自这些临床队列的多模式数据， 罗宾中心的实验室、项目和核心。