Phase 2 randomized total eradication of metastatic lesions following definitive radiation to the prostate in de novo oligometastatic prostate cancer (TERPs) trial.

Abstract

TPS275 Background: It is now recognized that some patients with “oligo,” or few sites of metastases, may have the potential to completely eradicate their disease with aggressive local therapy. There are recent encouraging randomized prospective data for total consolidation of macroscopic metastases through treatment intensification involving metastasis-directed therapy (MDT). Hypotheses include that radiation to primary prostate tumor and metastatic sites affects the natural history of metastasis by virtue of radiation effects on cancer cell autonomous pathways and tumor microenvironment/normal tissue pathways. This study aims to evaluate the utility of the addition of MDT to the evolving standard of care treatment for de novo low volume metastatic prostate cancer (PCa) patients. This study will evaluate the efficacy of best systemic therapy (BST) and primary prostate radiation (XRT) versus BST, XRT and stereotactic ablative radiation therapy (SABR) MDT. Discovery correlatives associated with clinical outcome will be assessed by collection of including, but not limited to: circulating tumor cells, immunologic biomarkers, microbiota and radiomics. Methods: This study is a multi-site, non-blinded, randomized Phase II trial in patients with oligometastatic PCa. Men with de novo histologically confirmed (at any site) oligometastatic PCa (<3 metastases on standard imaging or <5 on Axumin/Choline/PSMA-PET/CT) will be randomized (1:1) to BST + XRT versus BST + XRT + SABR MDT. BST and XRT will be administered for all men in the first 3-months, and radiation treatment will be completed within the first 150 days. A range of XRT treatment approaches are permitted but must deliver an EQD2 >75.6 Gy to the prostate. BST will allow standard and intensified androgen blockade. The trial will evaluate the addition of SABR MDT and explore several translational and imaging correlatives. Subjects who meet eligibility criteria and qualify for enrollment will be stratified according to: (i) hormonal therapy vs intensified hormonal therapy; (ii) XRT vs XRT + primary prostate boost, and (iii) absence vs presence of bone metastasis. This study has been approved and began accrual on October 3rd, 2022, the Clinicaltrials.gov. Identifier: NCT05223803. We assume an accrual time of 24 months, with 24 months of additional follow-up time, and will randomize a total of 122 patients (61 patients in each arm). The primary endpoint with be to assess 2-year failure-free survival (FFS). Secondary endpoints will include toxicity, quality of life (QoL), time to locoregional progression, time to distant progression, time to new metastasis, radiographic progression-free survival, and duration of response. Clinical trial information: NCT05223803 .