Molecular Characterization Trial

分子表征试验

• 批准号: 10704709
• 负责人: OMAR MIAN
• 金额: $ 19.07万
• 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/10704709
• 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; Robin bird; Sampling; Site; Specimen; Squamous cell carcinoma; Statistical Methods; Surveys; Testing; Therapeutic; Time; Tissues; Treatment Efficacy; anti-PD-1; antitumor effect; 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了辐射治疗。 存在机会，迫切需要将新的生物学知识应用于辐射的优化 治疗及其与新兴的靶向抗塑性剂的结合。 CCF/Emory的核心 Robin U54中心是一项分支分子表征试验（MCT），以纵向收集 来自肌肉浸润性膀胱癌（MIBC）和头部患者的生物测量和多模式数据 放射疗法之前，期间和之后，颈部鳞状细胞癌（HNSCC）。这些分子 表征同类也旨在合并免疫调节组合疗法 作为护理标准的化学放映疗法，旨在通过整合来解决紧迫的翻译问题 这些试验在罗宾中心的核心和项目中进行。这些以免疫放射生物学为中心 “小N，高质体”研究队列，这将使我们能够解决与 生物学基础对组合式放射疗法的反应。检验的中心假设是 纵向收集临床注释的生物测量和来自接受治疗的患者的多模式数据 在MCT队列的放疗期间和之后，检查了基于辐射的免疫疗法和标准 护理化疗将为遗传，免疫和进化基础提供新的见解 治疗反应。在两个不同的癌症中审问关键问题的能力将放大我们的 识别抗辐射抗性的基于概括的分子机制的能力和 免疫调节活性。我们的具体目的是进行标本收集和表征试验 与2个队列：（1）（MCTA）：与同时sacituzumab govitecan（rad-sg）的自适应放射疗法（rad-sg） MIBC患者的膀胱保存和（2）IMRT重新辐照的II期试验以及并发和 辅助Nivolumab。相同的样本和数据采集将从两个平行的队列中获得 护理标准顺铂加RT治疗的患者（每个部位n = 20）。高级的总体目标 该MCT中的内容研究队列是严格剖析效率的共同机制和驱动因素 两种癌症中最有希望的基于辐射的组合的抗性。我们将解决知识 与免疫调节反应的遗传，免疫学和分子进化基础有关的缺口 通过无缝整合来自这些临床队列的多模式数据的组合疗法 罗宾中心的实验室，项目和核心。