Quantifying and Personalizing the Clinical Benefit of Metastasis-Directed Therapy in Men with De Novo Oligometastatic Prostate Cancer

量化和个性化转移定向治疗对患有新发寡转移性前列腺癌的男性的临床益处

• 批准号: 10153007
• 负责人: Daniel Eidelberg Spratt
• 金额: $ 51.33万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-14 至 2027-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10153007
• 关键词: Ablation; Address; African American; Aftercare; American; Androgen Receptor; Bioinformatics; Biological Markers; Biometry; Biopsy; Biopsy Specimen; Blood; Blood Cells; Cancer Etiology; Castration; Cessation of life; Clinical; Clinical Management; Clinical Trials; Collection; Country; Data; Diagnosis; Disease; Enrollment; Extramural Activities; FOLH1 gene; Failure; Genomics; Goals; Heterogeneity; Histologic; Image; Incidence; Individual; International; Intramural Research Program; Malignant Neoplasms; Malignant neoplasm of prostate; Metastatic Prostate Cancer; Modeling; Molecular; Molecular Profiling; Neoplasm Circulating Cells; Neoplasm Metastasis; Newly Diagnosed; North America; PET/CT scan; Patients; Pattern; Phase; Positron-Emission Tomography; Prognostic Marker; Prostatectomy; Quality of life; Radiation therapy; Radical Prostatectomy; Randomized; Randomized Controlled Trials; Receptor Signaling; Recording of previous events; Research; Resistance; Resources; Sampling; Site; Specimen; Systemic Therapy; Testing; Therapeutic Trials; Time; Tissues; Translations; United Kingdom; United States National Institutes of Health; Validation; Work; X-Ray Computed Tomography; arm; biomarker signature; bone imaging; burden of illness; cell free DNA; chemotherapy; clinical center; exome; experience; feature extraction; imaging biomarker; imaging modality; imaging program; improved; inhibitor/antagonist; liquid biopsy; men; molecular imaging; molecular marker; molecular subtypes; neoplastic cell; next generation; novel; patient biomarkers; personalized medicine; phase II trial; phase III trial; predicting response; predictive marker; primary endpoint; prospective; prostate biopsy; radiomics; randomized trial; response; response biomarker; standard of care; transcriptome; treatment response

Project Summary/Abstract The long-term goal of this project is to determine the clinical impact of metastasis-directed radiotherapy (MDT) in men with de novo oligometastatic prostate cancer (PCa), and identify which men may be cured and benefit most from MDT. We aim to achieve this goal through the conduct of a phase 3 randomized controlled trial with prospective imaging and biospecimen (e.g. tissue and blood) collection. This trial is novel in that it is a randomized North American sub-study (n=200) of the next arm (Arm M) of the international landmark multi- arm, multi-stage, STAMPEDE trial. The ability to conduct this trial with comprehensive biospecimen collection and imaging analysis will be achieved through our unique research team across extramural and intramural centers, comprised of experts in prognostic and predictive biomarker signature identification, bioinformatics, biostatistics, genomics, imaging, and clinical trial execution. We will leverage the opportunity for North America to participate in the STAMPEDE trial to not simply identify the true impact of MDT in the first ever large phase 3 trial testing MDT in PCa, but use this one of a kind clinical trial working with the NCI to develop the first predictive biomarkers of benefit of MDT using radiomics of conventional and molecular PET imaging, as well as sequencing of primary, metastatic, and liquid biopsies. This goal will be carried out through three specific aims. Aim 1 will focus on the conduct of the phase 3 randomized North American sub-study to determine if the addition of MDT to standard systemic therapy and treatment of the primary improves failure-free survival. Five centers will participate, including the NIH Clinical Center. These patients will all be included in the international STAMPEDE trial with the primary endpoint of overall survival. Aim 2 will leverage the baseline CT and bone scans collected on all patients, as well as a subset that will be sent to the NCI to have pre-treatment 18F- DCFPyL PET/CT scans performed (n=50). Radiomic analyses and image feature extraction will be performed, and this information will be used to identify which men benefit most from MDT. We hypothesize that a subset of men will benefit most from MDT and be identifiable through an imaging biomarker. Aim 3 will utilize the baseline prostate biopsy, metastatic biopsies, radical prostatectomy specimens, and liquid biopsies (circulating tumor cells and cell-free DNA), to annotate the molecular landscape of oligometastatic PCa. This data will then be used to develop a predictive biomarker to identify which men benefit most from MDT. International patient samples will be banked for later validation. We hypothesize that a discrete molecular profile will characterize which men are most likely to be cured from MDT. The impact of this work is extremely large, as it has the potential to cure a currently incurable subset of men with metastatic PCa. Successful completion of these aims would result in predictive biomarkers that could directly impact the clinical management of men with oligometastatic PCa, and transform current treatment paradigms.

项目总结/文摘