Evolution of Hypofractionated Stereotactic Irradiation for Radio-Resistant Brain Metastases From D1-3-5 to D1-2-3
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 264
- 试验地点
- 1
- 主要终点
- Local control of brain metastases at 6 months
研究概览
简要总结
The goal of this prospective, multi-center, randomized double-arm clinical trial is to demonstrate a benefit in term of local control of a shorter spread of hypofractionated stereotactic radiotherapy at D1-2-3 vs D1-3-5, in the treatment of "radioresistant" Brain Metastases (BM). This trial aims to recruit patients with 1 to 5 unoperated BM originating from radioresistant primary sites. Patients will be randomly assigned to either the D1-3-5 radiotherapy arm or the D1-2-3 radiotherapy arm. Stereotactic brain irradiation will be administered at a dose of 33 Gy delivered in 3 fractions.
详细描述
Brain metastases (BM), originating from various primary tumors, are associated with decreased progression-free survival, overall survival, and neurological function. Stereotactic radiotherapy offers a precise and targeted approach to treat BM while minimizing cognitive side effects. Studies have shown comparable local control rates to surgery and conventional radiotherapy, but radioresistant cancers exhibit lower response rates whatever the technique of radiotherapy. The radiobiological implications of treatment duration in brain stereotactic irradiation remain understudied, resulting in a lack of available data. However, there is potential for a shorter irradiation duration to enhance tumor control without an accompanying increase in treatment-related toxicity. This study aims to demonstrate a benefit in terms of local control of a shorter spread of hypofractionated stereotactic radiotherapy at D1, D2, D3 vs D1, D3, D5, in the treatment of radioresistant brain metastases.
This prospective, multi-center, randomized, double-arm clinical trial aims to recruit patients with 1 to 5 unoperated brain metastases originating from radioresistant primary sites. Patients will be randomly assigned to either the D1,3,5 radiotherapy arm or the D1,2,3 radiotherapy arm and will be followed for 2 years. Stereotactic brain irradiation will be administered at a dose of 33 Gy delivered in 3 fractions at the isocenter.
The primary endpoint of the study is the assessment of local control at 6 months per brain metastasis. Secondary endpoints include evaluating cerebral control, overall survival, radionecrosis rate, quality of life, neurological function, and treatment-related toxicity.
A more condensed treatment approach may exploit the radiobiological properties of tumors, potentially increasing their sensitivity to radiation while minimizing the opportunity for tumor repopulation. Moreover, reducing treatment duration also has the potential to improve the patient's quality of life by minimizing fatigue towards the end of the irradiation course.
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
- None
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
- •Patients with one or more unoperated brain metastases (1-5) originating from radioresistant primary locations, including melanoma, kidney, digestive, sarcoma, and prostate *
- •Karnofsky Performance Status (KPS) greater than 50% (Annex 3).
- •Absence of major psychiatric conditions in the medical history that may interfere with follow-up, based on the investigator's judgement.
- •Proficiency in understanding French.
- •Signed informed consent.
- •For the ancillary study only: Patients included in the SISMIC study at centers with adequate resources and who have agreed to participate in the optional ancillary study.
- •Note: Patients who have had one or more surgery for metastasis removal and also have unresectable metastases are eligible for inclusion. Irradiation of the operating bed will follow the same treatment regimen as existing metastases but will not be considered for the evaluation of local control.
排除标准
- •Pregnant or breastfeeding women
- •An unoperated brain metastasis whose maximum diameter is > 3.5 cm
- •Patients deprived of liberty or under guardianship (including curatorship).
- •Patients with a history of cerebral radiotherapy.
- •Patients with known allergy to gadolinium.
- •Contraindication to magnetic resonance imaging (MRI).
结局指标
主要结局
Local control of brain metastases at 6 months
时间窗: at 6 months
Local control at 6 months per brain metastasis evaluated with magnetic resonance imaging (MRI)
次要结局
- Radionecrosis-free survival(according to local practices until death from any cause or lost to follow-up or until 24 months, whichever came first)
- Local control of brain metastases at 12, 18 and 24 months(at 12, 18 and 24 months)
- Cerebral control at 12, 18 and 24 months(at 12, 18 and 24 months)
- Overall survival(From the date of randomization until the date of death from any cause, loss to follow-up, or 24 months, whichever occurs first)
- Progression-free survival(According to local practices until the date of first documented progression or the date of death from any cause or until 24 months, whichever occurs first)
- Risk of leptomeningeal dissemination(according to local practices until death from any cause or lost to follow-up or until 24 months, whichever came first)
- Patient Safety(From the date of randomization until the date of death from any cause, loss to follow-up, or 24 months, whichever occurs first)
- Patient Quality of life(Before radiotherapy, then at 3, 6, 12, 18 and 24 months from randomization)
- Cognitive decline assessment(at baseline (before radiotherapy), then at 3, 6 and 12 months from randomization)
- Patient Safety according to Patient Reported Outcome(From the date of randomization until the date of death from any cause, loss to follow-up, or 24 months, whichever occurs first)