2841 - Total RadIoTherapy of Oligometastatic caNcerS (TRITONS): A Randomized Phase III Trial of Stereotactic Ablative Radiotherapy for =10 Metastatic Sites in Patients Receiving Systemic Therapy
Presenter(s)
E. M. Qiao1, L. J. Wei2, A. Dornisch1, R. Alexander3, A. Roder4, J. S. Kim1, A. Tanguilig3, C. C. Conlin5, J. Ye1, E. Al-Delaimy1, J. Liu1, N. Dhillon1, Y. W. Chen6, S. Choi6, H. Patel6, J. M. Randall6, B. S. Rose1, R. Shatsky6, M. Sherer1, T. F. Stewart6, R. R. Mckay6,7, and T. M. Seibert1,8; 1Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA, 2Harvard T.H. Chan School of Public Health, Boston, MA, 3Moores Cancer Center, UC San Diego Health, La Jolla, CA, 4Department of Urology, Centre for Cancer and Organ Diseases, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark, 5Department of Radiology, University of California San Diego, La Jolla, CA, 6Division of Hematology Oncology, University of California San Diego, La Jolla, CA, 7University of California, San Diego, La Jolla, CA, 8Research Service, VA San Diego Healthcare System, San Diego, CA
Purpose/Objective(s): The oligometastatic state is characterized by a limited number of metastatic sites and may represent a biologically distinct entity with potential sensitivity to treatment intensification. Randomized studies support comprehensive metastasis-directed therapy (MDT) with stereotactic ablative radiotherapy (SABR) in selected oligometastatic patients. SABR-COMET showed a significant improvement in 5-year overall survival (OS) for patients receiving SABR-based MDT compared with standard palliative care (Palma et al. 2020). Additional phase II trials in non-small cell lung cancer, prostate, and pancreas cancers have shown longer median progression free survival (PFS) when adding SABR to standard of care (SOC) systemic therapy (Tsai et al. 2024; Sherry et al. 2025; Ludmir et al. 2024). However, negative trials such as NRG-BR002 (Chmura et al. 2022) caution against routine use of SABR for all oligometastatic patients, and current data is limited by small cohorts, selected histologies, and inconsistency in systemic therapy use. Although ongoing phase III studies (Olson et al. 2020; Palma et al. 2019) are expanding the evidence base, clinical uncertainty persists given the heterogeneity of oligometastatic states (de novo, oligoprogressive, oligorecurrent, etc.) To help address this gap, Total RadIoTherapy of Oligometastatic caNcerS (TRITONS) is a multicenter, investigator-initiated phase III randomized trial evaluating SABR as MDT in oligometastatic patients receiving systemic therapy with up to 10 active metastatic sites.
Materials/Methods: Three hundred patients with oligometastatic (de novo or recurrent) or oligoprogressive cancer will be enrolled. Participating centers include academic centers in the United States and Denmark. Participants are randomized 1:1 between SOC systemic therapy vs. SOC + SABR to all sites of metastatic disease. Preferred SABR regimens include 20 grays (Gy) in 1 fraction, 24 Gy in 2 fractions, 30 Gy in 3 fractions, and 35 Gy in 5 fractions. Additionally, 50 Gy in 10 fractions and conventionally fractionated radiotherapy are allowed if required to minimize toxicity. The primary endpoint is PFS at 2 years determined radiologically by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Key secondary endpoints include OS at 3 years, all grade toxicity, and grade =3 toxicity. Eligible patients will be age 18+ years, with newly diagnosed or progressive metastatic disease, 1-10 sites of metastases visible on imaging (= 1 outside brain parenchyma), and starting systemic therapy within 6 months prior to randomization. Patients with markers of diffuse disease (e.g. leptomeningeal disease, malignant ascites) or any unresected metastasis >5cm in diameter or >3cm in the brain will be excluded. Enrollment began in November 2024 with written informed consent obtained from 56 participants thus far. Clinical trials identifier: NCT06587490, 9/19/2024.
Results: TBD
Conclusion: TBD