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) 的转移能力表现为一系列疾病，其中包含 寡转移状态，其中转移的数量和位置有限 放射的重要性。 现在正在整合寡转移性前列腺癌中的所有肿瘤沉积物，以防止进一步的转移性播散 得到了经常性环境中小型随机研究的支持，但在从头空间中的效用尚不清楚。 巴尔的摩 ORIOLE 单独、高度集中、高剂量立体定向消融放射 (SABR) 随机试验 与寡转移性 PCa 的观察相比，放射治疗显示出无进展生存期 (PFS) 的益处 此外，我们利用最先进的基因组分析技术证明了辐射。 产生的全身免疫反应可能预测患者从 SABR Total 中获益。 尚未在 PCa 的从头寡转移空间中测试巩固放射方法。 我们提出这个首次人体机会来了解微转移性疾病与 宏观疾病放疗后的原发性 PCa 有潜力：(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； 对于这一提案，我们将利用即将激活的随机化资源。 针对新发寡转移男性的完全放射巩固试验 – 第 2 期随机完全根除 新生寡转移性前列腺癌中前列腺明确放射后的转移病灶 (TERPS) 试验是一项针对患有新发寡转移性 PCa 的男性的 II 期非盲、随机 1:1 试验。 最佳全身治疗 (BST) + 初次前列腺放疗 (XRT) 与 BST+XRT+ 立体定向治疗的比较 消融性放射转移定向治疗 (SABR MDT) 现在，定义可能的患者的策略。 需要使用当前的 U54 生物标志物才能从 SABR 转移定向治疗 (MDT) 中获益最多。 ROBIN Oligometasis (ROBIN OligoMET) 分子表征试验 (MCT) 提案将进行 这项针对男性新发寡转移患者进行 SABR MDT 的首次人体随机试验的相关研究 我们探索了宏观前列腺肿瘤支持生长并帮助培育未来。 此外，我们追求组织、成像和循环生物标志物可以识别男性。 从头 PCa 寡转移最受益于 SABR #1 – 验证预后预测。 使用立体定向消融辐射的首次人体随机试验来评估组织和液体生物标志物的能力 (SABR) 巩固患有新发寡转移去势敏感前列腺癌的男性。 目标 #2 – 至 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后预测能力 患有新发寡转移去势敏感前列腺癌的男性进行放射（SABR）巩固治疗。