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）的转移能力表现为沿着一系列疾病， 寡转移状态，其中转移的数量和位置有限。辐射的重要性 目前，在寡转移性PCa中巩固所有肿瘤沉积物以防止进一步转移性播散， 在复发背景下的小型随机研究支持，但在从头空间的效用是未知的。我们 巴尔的摩ORIOLE单独立体定向消融放射（SABR）、高聚焦、高剂量的随机试验 与在寡转移性PCa中的观察相比，放射治疗显示无进展生存期（PFS）获益为 只有SABR。此外，使用最先进的基因组分析技术，我们证明了辐射 导致全身免疫应答，可能预测患者从SABR中获益。总 巩固放射方法尚未在PCa的从头寡转移空间中进行测试。因此，在本发明中， 我们提出这个首次在人身上的机会，以了解微转移性疾病之间的相互作用， 肉眼可见疾病的放射巩固后的原发性PCa有可能：（1）发现新的 放射生物学对转移过程的影响;（2）为患有癌症的患者提供治疗范例。 原发性寡转移性前列腺癌对于这项建议，我们将利用资源，从一个即将启动的随机 原发性寡转移男性的全放疗巩固治疗试验-II期随机全根除 原发性少转移性前列腺癌中前列腺确定性放疗后的转移性病变 （TERPS）试验。TERPS是一项在原发性寡转移性PCa男性患者中进行的II期非盲、随机1：1试验。 接受最佳全身治疗（BST）+原发性前列腺放疗（XRT）与BST+XRT+立体定向治疗 消融性放射转移导向治疗（SABR MDT）。现在，定义可能会 从SABR转移导向治疗（MDT）中获益最多的患者需要使用生物标志物。目前U 54 ROBIN寡转移（ROBIN OligoMET）分子表征试验（MCT）计划进行 在新发寡转移性男性患者中进行的SABR MDT首次人体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生长，并有助于培养未来的 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 从SABR中获益最大的原发性PCa寡转移。目标#1 -验证预测性 使用立体定向消融放射的首次人体随机试验的组织和液体生物标志物的能力 （SABR）巩固与新发寡转移去势敏感性前列腺癌的男性。 目标#2 -目标 使用立体定向消融的首次人体随机试验验证放射组学的预测能力 放射（SABR）巩固与原发寡转移去势敏感性前列腺癌的男性。