DDTBMQ000011: Advance tumor volume change as measured by CT as a pharmacodynamic biomarker for new oncologic drug clinical trial therapy of solid tumors to Stage 2 of FDA biomarker qualification

DDTBMQ000011：将 CT 测量的肿瘤体积变化作为实体瘤新肿瘤药物临床试验治疗的药效生物标志物，推进至 FDA 生物标志物资格第 2 阶段

• 批准号: 10410101
• 负责人: Ying Tang
• 金额: $ 24.86万
• 依托单位: CCS ASSOCIATES, INC.
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10410101
• 关键词: DDTBMQ000011; Advance; tumor; volume; change

Project Summary/Abstract The overall objective of this project is to advance the biomarker qualification application DDTBMQ000011 from the current Stage 1 to Stage 2 of the FDA biomarker qualification process. The scope of this project is based on recommendations from the FDA BQP review team that were communicated in the Determination Letter for accepting the legacy biomarker qualification proposal into the 507 Process, on additional advice received from the subsequent debriefing meeting, and on FDA guidance documents. A FDA BQP-suggested study will be conducted to assess agreement between the QIBA Profile’s CT volumetry biomarker definition of change (CTvol) and the RECIST system using the categories of responsive, stable, or progressive disease. Disagreements between the two approaches will be further broken down as: (i) substantive disagreement, where the disagreement between RECIST and CT volumetry cannot be attributable to improved sensitivity with CT volumetry and (ii) disagreement potentially due to improved sensitivity with CT volumetry. Factors predictive of disagreement will be identified. The null hypothesis is that the proportion of lesions with substantive disagreement is >15%; the alternative hypothesis is that the proportion of lesions with substantive disagreement is <15%. Images will be retrospectively collected from prior studies of subjects undergoing serial CT imaging in Phase 3 drug trials. Three readers will be recruited with very different levels of experience to participate in a prospective reader study of 234 cases. Study readers will measure each target lesion on the baseline and follow-up scans using two image analysis software tools. Both unidimensional and volume measurements of each target lesion at each timepoint will be taken and recorded for each case. From these data, measurements of change will be constructed when the same reader makes the measurements at each time point, as well as when different readers make the measurement at baseline and follow-up. The estimates of change will then be classified into three categories (partial or complete response, stable, or progression) using the two approaches (RECIST and QIBA Profile claim). The disagreement in classification between the two approaches will be reported. Multiple-variable logistic regression models will be fit to assess contribution of lesion characteristics (size, shape, location), magnitude of change as measured by CTvol, scanner model, image analysis software, whether imaging was QIBA-Profile-conformant or not, and reader protocol (same or different reader at two time points). The proposed work has great potential to validate the reproducibility of an emerging quantitative imaging biomarker (i.e., CT volumetry) to more precisely determine tumor response or progression in therapy trials.

项目总结/摘要 本项目的总体目标是推进生物标志物资格申请 DDTBMQ 000011从FDA生物标志物鉴定过程的当前阶段1至阶段2。 本项目的范围基于FDA BQP审查小组的建议， 在接受遗留生物标志物资格申请的决定函中传达 根据后续汇报会议收到的其他建议， FDA指导文件。将进行FDA BQP建议的研究，以评估 QIBA Profile的CT容积测定生物标志物变化定义（CTvol）与 RECIST系统使用缓解、稳定或进展性疾病的类别。 这两种办法之间的分歧将进一步细分为：㈠实质性分歧 不一致，其中RECIST和CT容量测定之间的不一致无法归因 与CT容量测定的灵敏度提高和（ii）可能由于改进的 灵敏度与CT容积法。将确定预测不一致的因素。零 假设实质性不一致的病变比例>15%;备选方案 假设实质性不一致的病变比例<15%。图像将 从III期接受系列CT成像的受试者的既往研究中回顾性收集 药物试验将招募三位经验水平非常不同的读者参加一个 234例前瞻性阅片者研究。研究读片员将测量 使用两种图像分析软件工具进行基线和随访扫描。一维和 将在每个时间点测量每个靶病变的体积，并记录每个 案子从这些数据中，当同一个读者进行 每个时间点的测量值，以及不同读数员在 基线和随访。然后将变化估计数分为三类 （部分或完全缓解、稳定或进展），使用两种方法（RECIST和QIBA Profile claim）。将报告两种方法之间的分类差异。 将拟合多变量逻辑回归模型，以评估病变特征的贡献 (size、形状、位置）、CTvol测量的变化幅度、扫描仪型号、图像 分析软件，无论成像是否符合QIBA配置文件，以及读取器协议（相同 或在两个时间点的不同读取器）。拟议的工作具有很大的潜力，以验证 新兴的定量成像生物标志物的再现性（即，CT容积测定法）更精确地 在治疗试验中确定肿瘤反应或进展。