Role of ctDNA change as a response measure in the EA1183 patient population and how ctDNA changes correlate with metabolic response by serial FDG PET/CT

ctDNA 变化作为 EA1183 患者群体反应指标的作用以及 ctDNA 变化如何与连续 FDG PET/CT 的代谢反应相关

• 批准号: 10209080
• 负责人: Jennifer Marie Specht
• 金额: $ 42.22万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-15 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10209080
• 关键词: American College of Radiology Imaging Network; Biological Assay; Biological Markers; Blood; Categories; Clinic; Clinical; Clinical Trials; Collection; Data Set; Disease; Disease Progression; Eastern Cooperative Oncology Group; Enrollment; Future; Generations; Genomics; Goals; Guidelines; Image; Lesion; Liquid substance; Malignant Bone Neoplasm; Measurable Disease; Measurement; Measures; Metabolic; Metastatic Neoplasm to the Bone; Metastatic breast cancer; Methods; Modality; Monitor; Multi-Institutional Clinical Trial; Outcome; Outcome Study; PET/CT scan; Patients; Progression-Free Survivals; Residual Tumors; Resistance; Role; Scanning; Site; Systemic Therapy; Testing; Time; Tracer; Tumor Biology; Tumor Markers; X-Ray Computed Tomography; base; blood-based biomarker; bone; burden of illness; cancer therapy; circulating biomarkers; clinical practice; clinical predictors; design; experience; fluorodeoxyglucose positron emission tomography; genome sequencing; glucose metabolism; imaging approach; imaging biomarker; improved; liquid biopsy; malignant breast neoplasm; patient population; patient response; predicting response; prospective; response; skeletal-related events; tool; treatment response; tumor; tumor DNA; tumor metabolism; uptake; whole genome

Project Summary: Patients with bone dominant (BD) and bone only (BO) metastatic breast cancer (MBC) represent a large patient population1,2 who are often excluded from clinical trials using RECIST 1.1 as the primary response assessment because bone lesions are classified as non-measurable, non-target lesions3. Current blood-based biomarkers such as tumor markers (CA15.3, CA27.29 and CEA) have similarly shown limited utility in assessing response to therapy in patients with MBC. There is therefore an important need for better measures of therapeutic response for patients with BD MBC. EA1183 FEATURE is a prospective, multicenter clinical trial approved by the NCI and sponsored by ECOG-ACRIN designed to evaluate the value of serial FDG-PET/CT to assess response in BD MBC. The trial will test the ability of tumor metabolic changes to predict the clinically meaningful outcomes of progression free survival (PFS) and time to skeletal-related event (tSRE). Measurement and characterization of ctDNA provides an option of non-invasively evaluating both disease burden and emergence of genomic changes in tumor biology. We propose to integrate fluid-based tumor monitoring (by serial collection of circulating tumor DNA, ctDNA) and FDG-PET/CT imaging to determine if these biomarkers, separately or combined, can predict a response to therapy for in patients with BO or BD MBC participating in the EA1183 FEATURE trial. We will also assess the extent to which FDG-PET/CT, ctDNA, or both can predict PFS as early as 4 weeks into therapy. We hypothesize that integration of imaging (FDG-PET/CT) and fluid-based, liquid biopsy (ctDNA) assays may permit characterization of therapy response for patients with BO and BD MBC in advance of currently used methods, possibly as early as 4 weeks. This R01 proposal will provide support for additional objectives in EA1183, which are the aims of our proposal: 1.) to assess ability of qualitative and quantitative changes in serial ctDNA measures to predict PFS and time to SRE in patients with BO or BD MBC beginning new systemic therapy in EA1183; 2) to determine if early metabolic changes in bone metastases assessed by FDG-PET/CT at 4 weeks after start of systemic therapy predict PFS and tSRE in patients with BO or BD MBC; 3) to evaluate the relationship between changes in ctDNA and metabolic response as assessed by FDG-PET/CT and to test the combined ability of FDG-PET/CT and ctDNA at 4 and 12 weeks after the start of new systemic therapy to predict PFS and SRE. The outcome of this study will be the generation of robust response endpoints for BD MBC to provide access to clinical trials and guide clinic al practice for the large group of patients with this type of MBC.

项目概要： 骨显性 (BD) 和仅骨 (BO) 转移性乳腺癌 (MBC) 患者占很大比例 经常被排除在使用 RECIST 1.1 作为主要反应的临床试验之外的患者群体1,2 评估，因为骨病变被归类为不可测量的非目标病变3。目前以血液为基础 肿瘤标志物（CA15.3、CA27.29 和 CEA）等生物标志物在治疗中同样显示出有限的效用。 评估 MBC 患者对治疗的反应。因此，迫切需要采取更好的措施 BD MBC 患者的治疗反应。 EA1183 FEATURE 是一项前瞻性、多中心临床试验 经 NCI 批准并由 ECOG-ACRIN 赞助，旨在评估系列 FDG-PET/CT 的价值 评估 BD MBC 中的反应。该试验将测试肿瘤代谢变化预测临床疗效的能力 无进展生存期 (PFS) 和骨骼相关事件时间 (tSRE) 的有意义的结果。 ctDNA 的测量和表征提供了一种非侵入性评估这两种疾病的选择 肿瘤生物学中基因组变化的负担和出现。我们建议整合基于液体的肿瘤 监测（通过连续收集循环肿瘤 DNA、ctDNA）和 FDG-PET/CT 成像以确定是否 这些生物标志物，单独或组合，可以预测 BO 或 BD 患者对治疗的反应 MBC 参与 EA1183 FEATURE 试验。我们还将评估 FDG-PET/CT、 ctDNA 或两者均可在治疗后 4 周预测 PFS。我们假设成像的整合 (FDG-PET/CT) 和基于液体的液体活检 (ctDNA) 分析可用于表征治疗反应 对于 BO 和 BD MBC 患者，提前目前使用的方法，可能最早 4 周。这 R01 提案将为 EA1183 中的其他目标提供支持，这些目标是我们提案的目标：1.) 评估系列 ctDNA 测量的定性和定量变化的能力，以预测 PFS 和 SRE 时间 在 EA1183 中开始新的全身治疗的 BO 或 BD MBC 患者； 2）确定是否早期代谢 全身治疗开始后 4 周时通过 FDG-PET/CT 评估的骨转移变化可预测 PFS BO 或 BD MBC 患者的 tSRE； 3）评估ctDNA变化与 通过 FDG-PET/CT 评估代谢反应并测试 FDG-PET/CT 和 ctDNA 的综合能力 在新的全身治疗开始后 4 周和 12 周进行预测，以预测 PFS 和 SRE。这项研究的结果 将为 BD MBC 生成稳健的反应终点，以提供临床试验和指南 针对大量此类 MBC 患者的临床实践。