Randomized Evaluation of Neoadjuvant Stereotactic Radiosurgery (SRS) and Multi-fraction SRS Alone for the Treatment of Large Brain Metastases: A Polish Multicenter Trial Protocol
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 98
- 主要终点
- Central nervous system (CNS) composite event (CE)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 years.
- •At least one brain metastasis appropriate for resection and not previously treated with SRS.
- •Lesions ≥2.5 cm and ≤6 cm in largest dimension.
- •Index lesion(s) will be treated, as outlined in the treatment section of the protocol.
- •Seen by a neurosurgeon or radiation oncologist and judged to be appropriate for participation in this study, including the ability to tolerate Neo-SRS, i.e., the ability to lie flat in a stereotactic head mask.
- •Any non-index lesion or lesions for which there is no possible resection must measure ≤4.0 cm in maximal dimension on the contrast MRI or CT brain scan obtained ≤35 days prior to pre-registration. Unresected lesions will be treated with SRS or mfSRS.
- •MRI confirms 1-10 lesions, one of which one is the index lesion. Each non-index lesion (up to nine) must measure ≤4 cm in maximal extent on contrast MRI and not otherwise require resection.
- •Known active or history of invasive primary non-central nervous system (CNS) cancer based on a documented histopathological diagnosis within the past three years.
- •Patient can tolerate surgery and SRS.
- •History/physical examination within 14 days prior to registration.
- •A negative urine or serum pregnancy test (in persons of childbearing potential, defined as any person who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal for at least 12 consecutive months) within ≤14 days prior to registration.
- •Participants who are sexually active must agree to use medically acceptable forms of contraception during treatment during this study to prevent pregnancy.
- •The patient or a legally authorized representative must provide study-specific informed consent prior to study entry.
排除标准
- •No resectable lesion ≥2.5 cm.
- •Unresectable >4 cm lesion.
- •Previous whole brain irradiation.
- •Progressive brain lesion treated with SRS.
- •Previous resection of brain metastases.
- •Leptomeningeal disease.
- •Lesion diameter >6.0 cm, or more than 20 lesions in the brain.
- •Required emergency decompressive surgery for life-threatening intracranial hypertension (with a preference towards adjuvant SRS/mfSRS protocols).
- •Prior diagnosis of malignant brain tumor.
- •Pediatric patients (age <18 years), pregnant women, and patients who are unable to give informed consent will be excluded.
结局指标
主要结局
Central nervous system (CNS) composite event (CE)
时间窗: From date of randomization to the date of a documented LR, SRN, or LMD, whichever comes first, assessed up to 12 months
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.
次要结局
- Overall survival (OS)(From date of randomization to the date of death or 12 months, whichever comes first)
- Progression-free survival (PFS)(From date of randomization to the date of death or 12 months, whichever comes first)
- Incidence of adverse events (any grade)(From date of randomization to the date of death or 12 months, whichever occurs first)
- Incidence of grade ≥3 adverse events(From date of randomization to the date of death or 12 months, whichever occurs first.)
- Health-related quality of life (EORTC QLQ-C30)(From date of randomization to the date of death or 12 months, whichever occurs first)
- Brain-specific quality of life (EORTC QLQ-BN20)(From date of randomization to the date of death or 12 months, whichever occurs first.)
研究者
Maciej Harat
Associate Professor of Radiation Oncology
Prof. Franciszek Lukaszczyk Memorial Oncology Center