Prognostic Models of Clinical Outcomes In Men With Castration Resistant Prostate

去势抵抗性前列腺男性临床结果的预后模型

• 批准号: 8188071
• 负责人: SUSAN HALABI
• 金额: $ 21.53万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-06 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8188071
• 关键词: Algorithms; Cancer Patient; Caring; Castration; Chemotherapy-Oncologic Procedure; Clinical; Clinical Treatment; Clinical Trials; Communities; Complex; Data; Data Set; Dependence; Development; Disease; Enrollment; Ensure; FDA approved; Future; Goals; Heterogeneity; Individual; Malignant neoplasm of prostate; Medical; Modeling; Motivation; Outcome; Pathway interactions; Patient Care; Patients; Persons; Pharmaceutical Preparations; Phase; Phase II/III Trial; Phase III Clinical Trials; Predictive Factor; Prednisone; Prognostic Factor; Progression-Free Survivals; Prostate; Prostate-Specific Antigen; Randomized; Reporting; Resistance; Resources; Staging; Subgroup; Surrogate Markers; Testing; Time; Toxic effect; Tumor Burden; catalyst; chemotherapy; clinical practice; clinically relevant; design; docetaxel; improved; innovation; men; men' s group; model development; novel; outcome forecast; prognostic; response; standard of care; tool; tumor

DESCRIPTION (provided by applicant): The dilemma in treating men with castration resistant prostate cancer (CRPC) lies not only in the heterogeneity of the disease but also the spectrum of patients that have the disease. Considerable energy has been dedicated to understanding tumor heterogeneity and developing prognostic models of clinical outcomes in men with CRPC who are chemotherapy naive. The identification of prognostic factors of clinical outcomes in men with CRPC who failed frontline chemotherapy has not, however, been investigated. Such identification is increasingly important due to the large number of patients who not only fail frontline chemotherapy but have excessive toxicity due to docetaxel. We anticipate that the same patient may need different models (prognostic calculators) at different stages of their care pathway as more prognostic information on that person's condition accumulates. The specific aims in this proposal are: 1) to develop a prognostic model that will predict overall survival (OS) in men with CRPC who failed first line chemotherapy. The model will be validated for predictive accuracy using an independent dataset. 2) To develop a prognostic model that will predict progression-free survival (PFS) in CRPC men who failed first line chemotherapy. The model will be validated for predictive accuracy using an independent dataset. 3a) To determine if e 30% decline in prostate specific antigen (PSA) at 3-months following treatment with cabazitaxel, the only FDA approved drug for treating men who failed frontline chemotherapy, is a valid surrogate marker of OS. 3b) to develop and validate a prognostic model that will predict post-therapy decline in PSA (e30% decline from baseline at 3-months). 4) To test for the dependence between time to progression and OS using the TROPIC trial. Innovation: This study has a high degree of innovation because of its strong potential to positively impact the design and conduct of future trials in PC. In particular, this study will be the first to identify and validate models of clinical outcomes and will incorporate data from the two largest phase III trials of men with advanced CRPC who failed frontline chemotherapy. These models are completely absent for the growing group of men who have received frontline chemotherapy and are considering secondary chemotherapy. The development of these models will facilitate discussions with CRPC patients, as well as help integrate these models into the design, conduct and analysis of new clinical trials in PC and patient care. PUBLIC HEALTH RELEVANCE: Prognostic models are not available for the burgeoning group of men who have received one regimen of chemotherapy, and are considering secondary chemotherapy. If these results are validated, our models can be used prospectively in randomized phase II & phase III trials to ensure that the treatment groups being evaluated are comparable. Further, they can assist in identifying subgroups of men with CRPC with particularly good or poor prognoses for whom therapy can be subsequently tailored. These models will serve as prediction tools that can be easily and rapidly implemented in clinical practice.

描述（由申请人提供）：治疗男性去势抵抗性前列腺癌（CRPC）的困境不仅在于该疾病的异质性，还在于患有该疾病的患者范围。我们投入了大量精力来了解肿瘤异质性，并开发未接受过化疗的 CRPC 男性临床结果的预后模型。然而，尚未对一线化疗失败的 CRPC 男性临床结果的预后因素进行研究。由于大量患者不仅一线化疗失败，而且因多西紫杉醇产生过度毒性，这种识别变得越来越重要。我们预计，随着更多关于该患者病情的预后信息的积累，同一患者在其护理路径的不同阶段可能需要不同的模型（预后计算器）。该提案的具体目标是：1) 开发一种预后模型，用于预测一线化疗失败的 CRPC 男性患者的总生存期 (OS)。将使用独立数据集验证模型的预测准确性。 2) 开发一种预后模型，预测一线化疗失败的 CRPC 男性的无进展生存期 (PFS)。将使用独立数据集验证模型的预测准确性。 3a) 确定用卡巴他赛治疗 3 个月后前列腺特异性抗原 (PSA) 下降 30% 是否是 OS 的有效替代标志物，卡巴他赛是 FDA 批准的唯一用于治疗一线化疗失败男性的药物。 3b) 开发并验证一个预后模型，该模型将预测治疗后 PSA 的下降（3 个月时较基线下降 e30%）。 4) 使用 TROPIC 试验测试进展时间和 OS 之间的依赖性。创新性：这项研究具有高度的创新性，因为它具有对 PC 未来试验的设计和进行产生积极影响的强大潜力。特别是，这项研究将是第一个确定和验证临床结果模型的研究，并将纳入两项最大的 III 期试验的数据，这些试验的对象是一线化疗失败的晚期 CRPC 男性。对于越来越多接受一线化疗并正在考虑二次化疗的男性群体来说，这些模型完全不存在。这些模型的开发将促进与 CRPC 患者的讨论，并有助于将这些模型整合到 PC 和患者护理的新临床试验的设计、实施和分析中。 公共卫生相关性：对于已接受一种化疗方案并正在考虑二次化疗的新兴男性群体，尚无预后模型。如果这些结果得到验证，我们的模型可以前瞻性地用于随机 II 期和 III 期试验，以确保正在评估的治疗组具有可比性。此外，它们还可以帮助识别预后特别好或特别差的 CRPC 男性亚组，随后可以针对这些亚组制定治疗方案。这些模型将作为预测工具，可以在临床实践中轻松快速地实施。