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

基本信息

批准号：
8681186
负责人：
SUSAN HALABI
金额：
$ 23.16万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-07-06 至 2016-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8681186
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 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 castration resistant prostate cancer catalyst chemotherapy clinical practice clinically relevant design docetaxel improved innovation men men&apos s group model development novel outcome forecast prognostic response standard of care tool tumor

项目摘要

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.

描述（由申请人提供）：治疗耐cast割前列腺癌（CRPC）的男性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。大量能量致力于理解肿瘤异质性，并在化学疗法幼稚的CRPC男性中开发临床结局的预后模型。然而，尚未研究鉴定前线化学疗法失败的CRPC男性临床结果的预后因素。由于大量患者不仅失败了前线化疗，而且由于多西他赛而导致过多的毒性，因此这种识别越来越重要。我们预计，随着该人病情的更多预后信息会累积，同一患者可能需要不同模型（预后计算器）。该提案中的具体目的是：1）开发一种预后模型，该模型将预测一线化学疗法失败的CRPC男性的总体生存（OS）。该模型将通过独立数据集进行验证以进行预测精度。 2）开发一个预后模型，该模型将预测一线化疗失败的CRPC男性中无进展生存率（PFS）。该模型将通过独立数据集进行验证以进行预测精度。 3A）为了确定用Cabazitaxel治疗后3个月的前列腺特异性抗原（PSA）的E 30％，这是唯一获得FDA批准治疗前线化疗的男性的药物，是OS的有效替代标记。 3B）开发和验证预后模型，该模型将预测PSA后疗法后的下降（E30％的基线下降了3个月）。 4）使用热带试验测试时间对进展和OS的依赖性。创新：这项研究具有高度的创新，因为它具有积极影响PC中未来试验的设计和行为的强大潜力。特别是，这项研究将是第一个识别和验证临床结果模型的研究，并将结合两项最大的III期阶段试验的数据，该试验的高级CRPC男性未通过前线化学疗法。这些模型完全不存在接受一线化学疗法并正在考虑二级化疗的男性的成长组。这些模型的开发将有助于与CRPC患者进行讨论，并有助于将这些模型整合到PC和患者护理中新的临床试验的设计，进行和分析中。