Abstract
TPS5094 Background: ORIOLE is a randomized, non-blinded Phase II interventional study evaluating the safety and efficacy of SBRT in biochemically recurrent, oligometastatic, hormone-sensitive prostate cancer at 3 centers in the US. Patients will be stratified by clinical characteristics and randomized 2:1 to SBRT or observation. The primary clinical endpoint is progression at 6 months defined by PSA increase, radiologic or clinical evidence, ADT initiation, or death from any cause. Secondary endpoints include local control at 6 months, SBRT-associated toxicity and quality of life, and ADT-free survival. Imaging and laboratory correlates will characterize, in isolation, the effects of SBRT on oligometastatic disease. Methods: Eligible patients are hormone-sensitive, have undergone prior definitive treatment and recurred with 1-3 asymptomatic bone or soft tissue metastases diagnosed within 6 months, PSA doubling time (PSADT) < 15 months, ECOG performance status ≤ 2, and normal organ and marrow function. Minimization will be used to balance assignment by primary intervention, prior ADT, and PSADT. Accrual of 54 patients provides 85% power to detect a decrease in progression rate from 80% to 40% with type I error = 0.05 using one-sided Fisher’s exact test. Hazard ratios and Kaplan-Meier estimates of progression free survival, ADT free survival, and time to locoregional and distant progression will be calculated based on intention-to-treat. Local control will be assessed using RECIST 1.1 criteria. Withdrawal prior to 6 months will be counted as progression. Adverse events will be summarized and quality of life pre- and post-SBRT will be measured by Brief Pain Inventory. The investigational targeted imaging agent 18F-DCFPyL will be compared to bone scan and CT for identifying oligometastases before SBRT and monitoring disease response following SBRT. Biological alterations induced by SBRT will be investigated using circulating tumor cell analysis, deep sequencing of circulating tumor DNA, and T-cell repertoire profiling. A hereditary cancer assay will inform efforts to advance personalized screening and therapy. Clinical trial information: NCT02680587.
Highlights
We describe a randomized, non-blinded Phase II interventional study to assess the safety and efficacy of stereotactic ablative radiotherapy (SABR) for hormone-sensitive oligometastatic prostate adenocarcinoma, and to describe the biology of the oligometastatic state using immunologic, cellular, molecular, and functional imaging correlates. 54 men with oligometastatic prostate adenocarcinoma will be accrued
In the modern era with conventional imaging, oligometastatic hormone sensitive prostate cancer likely comprises a large number of men, possibly the majority of men following failed primary therapy [25,26,27,28]. Assuming these men are at a potentially curable state before castration-resistance develops, we need additional treatment strategies to re-examine this large cohort of men. Based on this emerging evidence, we propose a phase II study of SABR in patients with oligometastatic hormone sensitive prostate cancer
Complete Response (CR): Disappearance of all target lesions and Prostate specific antigen (PSA) below baseline Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum OR at least 1/3 of lesions are stable or resolved by bone scan AND PSA below baseline Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since treatment initiation OR the appearance of >1 new lesion(s) by bone scan OR PSA ≥25% above nadir or > 50 ng/ml
Summary
Non-blinded Phase II interventional study to assess the safety and efficacy of stereotactic ablative radiotherapy (SABR) for hormone-sensitive oligometastatic prostate adenocarcinoma, and to describe the biology of the oligometastatic state using immunologic, cellular, molecular, and functional imaging correlates. 54 men with oligometastatic prostate adenocarcinoma will be accrued. The primary clinical endpoint will be progression at 6 months from randomization with the hypothesis that SABR to all metastases will forestall progression by disrupting the metastatic process. The presence of an oligometastatic state, at which point metastases are limited in number and location, was originally proposed by Hellman and Weichselbaum, who suggested that these patients would benefit from effective local therapy in addition to systemic therapy [1]. The treatment of metastases depends on multiple factors including 1) the location of the primary tumor, 2) the size, number and location of metastases, 3) the availability and effectiveness of therapies (e.g. surgery, radiation, and chemotherapy), and 4) the patient’s functional status. Highly accurate radiation at tumorocidal doses can be delivered in 1 to 5 outpatient treatments [4,5,6,7,8]
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