Molecular Characterization Trial

分子表征试验

基本信息

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
项目类别：
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

项目摘要

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.

项目概要分子表征试验导航扩展样本调查以选择治疗方法 (ROBIN-NESTS) 摘要：大约一半的癌症患者在病程中接受放射治疗。在辐射优化中应用新的生物学知识存在机会和迫切需要治疗及其与新兴靶向抗肿瘤药物的组合是 CCF/Emory 的核心。 ROBIN U54 中心是一个分支分子表征试验 (MCT)，专注于纵向收集来自肌层浸润性膀胱癌 (MIBC) 和头颅癌患者的生物样本和多模式数据颈部鳞状细胞癌 (HNSCC) 在放疗之前、期间和之后进行这些分子治疗。特征队列的设计也纳入了免疫调节联合疗法作为护理标准放化疗，旨在通过整合来解决紧迫的转化问题这些试验贯穿罗宾中心的核心和项目，这些都是以免疫放射生物学为中心的。 “小N，高内容”研究队列将使我们能够解决与对联合放射治疗的生物学基础反应正在检验的中心假设是纵向收集临床注释的生物样本和之前接受治疗的患者的多模式数据， MCT 队列的放射治疗期间和之后检查基于放射的免疫疗法和标准护理放化疗将为遗传、免疫学和进化基础提供新的见解询问两种不同癌症的关键问题的能力将放大我们的治疗反应。识别抗辐射性背后的普遍分子机制的能力我们的具体目标是进行样本采集和表征试验。包含 2 个队列：(1) (MCTa)：采用同步 Sacituzumab Govitecan (RAD-SG) 的适应性放射治疗 MIBC 患者的膀胱保留和 (2) IMRT 再照射加同步和放疗的 II 期试验佐剂纳武单抗将从两个平行队列获得相同的样本和数据采集。顺铂加 RT 治疗患者的护理标准（每个中心 n=20）。本 MCT 中的内容研究队列旨在严格剖析功效和作用的常见机制和驱动因素我们将讨论对两种癌症最有希望的基于放射的组合的抵抗力。与免疫调节反应的遗传、免疫学和分子进化基础相关的差距通过无缝整合来自这些临床队列的多模式数据来进行联合治疗 ROBIN 中心的实验室、项目和核心。