Project 3: Extending Clinical Benefit by Selective Treatment of Resistant Lesions in mCRPC

项目 3：通过选择性治疗 mCRPC 耐药病变来扩大临床获益

基本信息

批准号：
10555402
负责人：
ROBERT JERAJ
金额：
$ 34.35万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-07-01 至 2028-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10555402
关键词：
Ablation Androgen Receptor Androgens Anxiety Area Castration Clinical Continuity of Patient Care Data Deterioration Disease Disease Progression Enrollment FOLH1 gene Feasibility Studies Generations Goals Heterogeneity Image Individual Lesion Location Medical Imaging Metastatic Prostate Cancer Methodology Modeling Neoplasm Metastasis Outcome PET/CT scan Pathway interactions Patient Care Patients Phase Ib Trial Positron-Emission Tomography Progression-Free Survivals Prostate Provider Radiation Radiation therapy Radio Resistance Signal Transduction Site Spinal Cord Systemic Therapy Technology Testing Therapeutic Clinical Trial Time Tracer Tumor Burden Universities Weight Wisconsin Work X-Ray Computed Tomography bone chemotherapy disorder control experience fluorodeoxyglucose positron emission tomography imaging study improved individual patient inhibitor innovation men molecular imaging new technology personalized approach prospective quantitative imaging radioligand radiological imaging response safety and feasibility therapy development therapy resistant treatment response virtual virtual clinical trial

项目摘要

PROJECT SUMMARY Development of treatment resistance is the main reason for disease progression in patients with mCRPC. What is under-appreciated is that many patients who are experiencing progression have the majority of individual lesions that continue to respond to therapy. Identification of resistant lesions would allow for administration of localized ablative therapies, especially if the systemic therapy is still effective for the majority of metastases. We hypothesize that selective treatment of resistant lesions (e.g. with stereotactic body radiation therapy) will extend duration of clinical benefit in men with mCRPC. We will identify resistant lesions by employing our unique advanced quantitative molecular image analytics - Quantitative Total Extensible Imaging (QTxI) which allows lesion-level assessment of treatment dynamics. We will test our hypothesis through the following aims: (1) To characterize resistance at early progression in men with mCRPC treated with second-generation androgen- signaling inhibitors by employing QTxI of PET/CT starting at nadir PSA response, PSA progression, and again in 12 weeks, (2) To conduct virtual selective radio-ablation study using different PET metrics for target lesion selection of resistant lesions and to model impact of radio-ablation on total tumor burden and anticipated improvement in clinical benefit and (3) To test clinical feasibility of radio-ablation using SBRT to selective resistant lesions in a prospective therapeutic clinical trial. This project is highly innovative as it explores lesion-level treatment resistance in mCRPC, uniquely characterized by our technology, as a treatment target. Assessment of resistance at the time of clinical progression is critical, as it triggers high anxiety in the patient and provider, and thus it is an urgent area of unmet clinical need. We will conduct the first trial of its kind to identify and treat resistant lesions in the setting of wide- spread metastatic disease with the goal of improving clinical benefit.

项目摘要治疗耐药性的发展是MCRPC患者疾病进展的主要原因。什么值得注意的是，许多经历进展的患者的大多数继续对治疗反应的病变。抗性病变的识别将允许给予局部的消融疗法，尤其是如果系统疗法仍然对大多数转移有效。我们假设选择性治疗耐药性病变（例如，立体定向的身体放射治疗）将延长MCRPC男性临床益处的持续时间。我们将通过使用我们的独特性来确定耐药性病变高级定量分子图像分析 - 定量总伸展成像（QTXI），允许病变级治疗动态评估。我们将通过以下目的检验我们的假设：（1）用第二代雄激素治疗的MCRPC男性在早期进展中的抗性表征通过使用Nadir PSA响应，PSA进展的PET/CT的QTXI，通过使用QTXI来传导抑制剂在12周内，（2）使用不同的宠物指标进行靶病变的虚拟选择性放射研究选择耐药性病变并模拟放射性对总肿瘤负担的影响，并预期改善临床益处和（3）测试使用SBRT的放射性开放的临床可行性前瞻性治疗临床试验中的抗性病变。该项目具有高度创新性，因为它探索了MCRPC病变级治疗的耐药性以我们的技术为特征，作为治疗目标。临床时的抗药性评估进展至关重要，因为它会触发患者和提供者的高焦虑，因此这是一个未满足的紧急领域临床需求。我们将在广泛的环境中进行此类试验，以识别和治疗抗性病变传播转移性疾病，目的是提高临床益处。