Phase 2 randomized Total Eradication of metastatic lesions following definitive Radiation to the Prostate in de novo oligometaStatic prostate cancer (TERPS) trial

在从头寡转移性前列腺癌 (TERPS) 试验中，对前列腺进行明确放射治疗后转移性病变的 2 期随机完全根除试验

• 批准号: 10515451
• 负责人: Phuoc T. Tran
• 金额: $ 36.74万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-04 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10515451
• 关键词: Address; Back; Baltimore; Biological Assay; Biological Markers; Biology; Castration; Cessation of life; Clinical; Clinical Data; Correlative Study; Data; Deposition; Disease; Distant Metastasis; Electromagnetic Energy; FOLH1 gene; Failure; Future; Genetic Transcription; Genomics; Growth; Image; Immune response; Liquid substance; Location; Malignant neoplasm of prostate; Metastatic Prostate Cancer; Methods; Microscopic; Molecular; Monitor; Mutation; Neoplasm Metastasis; Patients; Pattern; Peripheral; Phase; Plasma; Positron-Emission Tomography; Progression-Free Survivals; Prostate; Prostatic Neoplasms; Proteomics; Radiation; Radiation Dose Unit; Radiation Oncology; Radiobiology; Randomized; Recurrence; Research Design; Resources; Systemic Therapy; T cell receptor repertoire sequencing; T-Cell Receptor; T-Lymphocyte; Techniques; Testing; Tissues; X-Ray Computed Tomography; base; circulating biomarkers; experimental study; first-in-human; imaging biomarker; innovation; liquid biopsy; men; metabolomics; metastatic process; microbiome; novel; patient population; predictive marker; prognostic; programs; radiomics; randomized trial; response; response biomarker; tissue biomarkers; transcriptome sequencing; treatment response; trend; tumor

The metastatic capacity of prostate cancer (PCa) behaves along a spectrum of disease that contains an oligometastatic state where metastases are limited in number and location. The importance of radiation consolidation of all tumor deposits in oligometastatic PCa to forestall further metastatic dissemination is now backed by small randomized studies in the recurrent setting, but the utility in the de novo space is unknown. Our Baltimore ORIOLE randomized trial of stereotactic ablative radiation (SABR) alone, highly focused, high-dose radiation, versus observation in oligometastatic PCa demonstrated a progression-free survival (PFS) benefit of SABR alone. Furthermore, using state-of-the-art genomic profiling techniques we demonstrated that radiation resulted in a systemic immune response that could possibly predict patient benefit from SABR. Total consolidative radiation approaches have not been tested in the de novo oligometastatic space for PCa. Thus, we propose this first-in-man opportunity to understand the interplay between micrometastatic disease and the primary PCa following radiation consolidation of macroscopic disease has the potential to: (1) uncover novel radiobiology implications on the metastatic process; and (2) provide a curative paradigm for patients with de novo oligometastatic PCa. For this proposal, we will leverage resources from a soon to be activated randomized trial of total radiation consolidation for de novo oligometastatic men – Phase 2 randomized Total Eradication of metastatic lesions following definitive Radiation to the Prostate in de novo oligometaStatic prostate cancer (TERPS) trial. TERPS is a phase II non-blinded, randomized 1:1 trial of men with de novo oligometastatic PCa treated with best systemic therapy (BST) + primary prostate radiation (XRT) versus BST+XRT+ stereotactic ablative radiation metastasis-directed therapy (SABR MDT). Now, strategies to define the patients who may benefit the most from SABR metastasis-directed therapy (MDT) are needed using biomarkers. This current U54 ROBIN Oligometastasis (ROBIN OligoMET) Molecular Characterization Trial (MCT) proposal is to conduct correlative studies from this first-in-man randomized trial of SABR MDT in men with de novo oligometastatic prostate cancer. We hypothesize macroscopic prostate tumors support the growth of and help nurture future distant metastases. In addition, we hypothesize that tissue, imaging and circulating biomarkers can identify men with de novo PCa oligometastasis that benefit the most from SABR. AIM #1 – To validate prognostic-predictive ability of tissue and liquid biomarkers using the first-in-man randomized trial of stereotactic ablative radiation (SABR) consolidation in men with de novo oligometastatic castration-sensitive prostate cancer. AIM #2 – To validate prognostic-predictive ability of radiomics using the first-in-man randomized trial of stereotactic ablative radiation (SABR) consolidation in men with de novo oligometastatic castration-sensitive prostate cancer.

前列腺癌（PCA）的转移能力沿着一系列疾病的表现 少量转移状态，其中转移的数量和位置受到限制。辐射的重要性 现在，所有寡聚PCA中所有肿瘤沉积物的巩固以防止进一步的转移传播 在复发环境中的小型随机研究的支持下，但从头空间中的效用尚不清楚。我们的 单独的立体定向辐射（SABR）的巴尔的摩Oriole随机试验，高剂量 辐射，寡聚PCA中的观察结果表明，无进展生存（PFS）的好处 独自一人。此外，使用最先进的基因组分析技术，我们证明了辐射 导致系统性免疫反应，可以预测患者从SABR中受益。全部的 尚未在PCA的从头寡聚空间中测试巩固辐射方法。那， 我们提出了这个人类的第一个机会，以了解微转移性疾病与 宏观疾病辐射巩固后的主要PCA具有以下潜力：（1）发现新颖的 放射生物学对转移过程的影响； （2）为DE患者提供了一种治疗范例 Novo寡聚量pca。对于此提案，我们将利用即将激活的随机激活资源 从头寡量转移男性的总辐射整合试验 - 第2阶段随机根除 从头寡聚前列腺癌中前列腺的明确辐射后，转移性病变 （TERPS）试验。 TERPS是II期非盲，随机1：1从头寡聚PCA的男性的试验 用最佳全身疗法（BST）+主要前列腺辐射（XRT）与BST+ XRT+立体定向治疗 消融辐射转移指导的治疗（SABR MDT）。现在，定义可能的患者的策略 使用生物标志物，需要从SABR转移指导的治疗（MDT）中受益最大。当前的U54 罗宾寡聚（罗宾寡量）分子表征试验（MCT）提案是进行 来自NOKOMOTITATIT的男性SABR MDT的这一人类第一组随机试验的相关研究 前列腺癌。我们假设宏观前列腺肿瘤支持并帮助护理未来的生长 远处转移。此外，我们假设组织，成像和循环生物标志物可以识别男性 借助从NOVO PCA寡聚，从SABR中受益最大。目的＃1 - 验证预测性预测性 使用立体定向辐射的第一组随机试验组织和液体生物标志物的能力 （SABR）从头寡聚化cast割敏感的前列腺癌的男性的巩固。 目标＃2 - 使用立体定向擦除的第一组随机试验，验证放射素学的预后预测能力 从头寡量学cast割敏感的前列腺癌的男性中的辐射（SABR）巩固。