The prospective, two-arm, randomized, controlled, multicentric phase III RENESANS trial is designed to compare the efficacy and safety of neoadjuvant stereotactic radiosurgery (Neo-SRS) versus multi-fraction stereotactic radiosurgery (mfSRS) in patients with large brain metastases, with the primary objective of evaluating the incidence of central nervous system composite events.
The RENESANS trial compares the efficacy and safety of two treatment strategies for large brain metastases: neoadjuvant stereotactic radiosurgery (Neo-SRS) and multi-fraction stereotactic radiosurgery (mfSRS) alone. It is a prospective, two-arm, randomized (1:1), controlled, multicentric phase III trial conducted between September 30, 2025 and September 30, 2033 in multiple radiation oncology units in Poland. Study participants are patients with cancer and a Karnofsky performance status (KPS) \>60 who have at least one brain metastasis appropriate for resection, not previously treated with SRS, and measuring ≥2.5 cm and \<6 cm in the largest dimension. The intervention arms are: (i) neoadjuvant SRS (a single dose of 12-16 Gy SRS); and (ii) mfSRS alone (30 Gy delivered in 5 fractions). The primary outcome is the number of participants developing a central nervous system (CNS) composite event, defined as local recurrence of the treated lesions, symptomatic radiation necrosis of the treated lesions, or development of leptomeningeal disease. Secondary outcomes include overall survival (OS), progression-free survival (PFS), adverse events assessed according to NCI CTCAE version 5.0 criteria, and health-related quality of life (QoL) assessed using the EORTC QLQ-C30 and QLQ-BN20 questionnaires.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
98
Single dose of 12-16 Gy
30 Gy treatment in five fractions
Central nervous system (CNS) composite event (CE)
Number of participants experiencing a central nervous system (CNS) composite event (CE). A CNS CE is defined as the occurrence of at least one of the following events: local recurrence (LR) of a treated lesion, symptomatic radiation necrosis (SRN) of a treated lesion, or development of leptomeningeal disease (LMD). This is a composite endpoint analyzed as a single binary outcome per participant.
Time frame: From date of randomization to the date of a documented LR, SRN, or LMD, whichever comes first, assessed up to 12 months
Overall survival (OS)
OS is defined as the time between randomization and death due to any cause. Patients without an event will be censored at the date of last follow-up. Patients with no post-baseline follow-up for progression will be censored at the day of randomization. Median, six-month, and one-year OS will be measured
Time frame: From date of randomization to the date of death or 12 months, whichever comes first
Progression-free survival (PFS)
PFS is defined as the time from randomization until radiographic progression, based on Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria (including local recurrence and distant brain metastases), or death from any cause. Patients without an event will be censored at the date of last progression-free follow-up. Patients without post-baseline follow-up will be censored at the date of randomization. Median, 6-month, and 1-year PFS will be reported.
Time frame: From date of randomization to the date of death or 12 months, whichever comes first
Incidence of adverse events (any grade)
All treatment-related adverse events (AEs) will be recorded from screening until disease progression or death. Adverse events will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0. The number and proportion of participants experiencing at least one adverse event of any grade will be summarized by treatment arm.
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Time frame: From date of randomization to the date of death or 12 months, whichever occurs first
Incidence of grade ≥3 adverse events
The number and proportion of participants experiencing at least one treatment-related adverse event of grade 3 or higher, as defined by NCI CTCAE version 5.0, will be compared between treatment arms.
Time frame: From date of randomization to the date of death or 12 months, whichever occurs first.
Health-related quality of life (EORTC QLQ-C30)
Health-related quality of life will be assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30). Scores will be calculated according to the EORTC scoring manual and reported on a standardized scale from 0 to 100.
Time frame: From date of randomization to the date of death or 12 months, whichever occurs first
Brain-specific quality of life (EORTC QLQ-BN20)
Brain cancer-specific quality of life will be assessed using the EORTC Brain Cancer Module (QLQ-BN20). Scores will be calculated according to the EORTC scoring manual and reported on a standardized scale from 0 to 100.
Time frame: From date of randomization to the date of death or 12 months, whichever occurs first.