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: 10676858
• 负责人: Phuoc T. Tran
• 金额: $ 21.74万
• 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/10676858
• 关键词: Address; Baltimore; Biological Assay; Biological Markers; Biology; Castrate sensitive prostate cancer; 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; PET/CT scan; Patients; Pattern; Peripheral; Phase; Plasma; 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; 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 转移在数量和位置上受限的少转移状态。辐射的重要性 在少转移的前列腺癌中巩固所有的肿瘤沉积以防止进一步的转移扩散现在是 这项研究得到了小规模随机研究的支持，但在从头研究中的效用尚不清楚。我们的 巴尔的摩金莺立体定向消融放射(SABR)单独、高聚焦、高剂量随机试验 与少转移性前列腺癌的观察相比，放射治疗显示了以下优点： 仅SABR一家。此外，使用最先进的基因组图谱技术，我们证明了辐射 导致全身免疫反应，可能预测患者从SABR中受益。总计 巩固放射治疗方法还没有在前列腺癌的新生寡转移瘤空间中进行测试。因此， 我们提出了这一第一个人的机会来了解微转移疾病和 宏观疾病放射巩固后的原发PCA有可能：(1)发现新的 放射生物学对转移过程的影响；以及(2)为食道癌患者提供治疗范例。 Novo寡转移PCA。对于这项提案，我们将利用即将启动的随机方案的资源 全放疗治疗新发少转移瘤的临床试验--2期随机全根治 前列腺癌新发少转移性前列腺癌明确放射治疗后的转移性病变 (Terps)试验。TERPS是一项II期非盲法、随机、1：1的男性少转移性前列腺癌的试验 最佳全身治疗(BST)+直接前列腺放射治疗(XRT)与BST+XRT+立体定向治疗 消融性放射转移定向治疗(SABR MDT)。现在，定义哪些患者可能 从SABR中获益最多需要使用生物标记物进行转移定向治疗(MDT)。这款目前的U54 Robin寡转移瘤(Robin OdonoMET)分子特征试验(MCT)的建议是进行 SABR MDT在男性新发少转移瘤患者中的首例随机试验的相关性研究 前列腺癌。我们假设肉眼可见的前列腺癌支持生长并帮助培育未来 远处转移。此外，我们假设组织、成像和循环生物标记物可以识别男性 从SABR中获益最多的是从头开始的前列腺癌少转移。目标1-验证预测-预测 组织和液体生物标记物能力的立体定向消融放射首例随机试验 新发寡转移性去势敏感型前列腺癌患者的(SABR)巩固。 目标2--目标 应用首例立体定向消融随机试验验证放射组学的预后预测能力 新发寡转移性去势敏感型前列腺癌患者的放射(SABR)巩固。