Phase 1B multicenter study of the safety and efficacy of stereotactic body radiation therapy for extracranial renal cell carcinoma metastases in combination with tyrosine kinase inhibitors or checkpoint inhibitors (Volga study)

Background. Tyrosine kinase inhibitors (TKI) and checkpoint inhibitors (CI) have been established as effective treatment for mRCC, but only a minority of patients achieves complete response and additional strategies are necessary to improve the efficacy of these agents. We have designed a prospective phase 1b «Volga» study to determine the safety and efficacy of extracranial SBRT in patients with clear-cell mRCC. Methods. Patients were included if they had stable disease for at least 4 months on TKI or CI. SBRT was delivered to an organ with multiple comparable lesions, where one lesion was in the treatment target (target lesion) and the other lesion was intentionally left untreated (control lesion). Dose of radiation and number of fractions were determined based on target lesion localization and the proximity of organs at risk. Response in both target and control lesions was scored using RECIST 1.1 criteria at least 2 months after completion of SBRT. Primary endpoint was the rate of adverse events of SBRT and secondary endpoints included the rate of reduction in target lesion size and time to progression of the first (target) and the second (control) lesions...