Radiotherapy of Multiple Brain Metastases Using AGuIX® Gadolinium-chelated Polysiloxane Based Nanoparticles: a Prospective Randomized Phase II Clinical Trial.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 106
- 试验地点
- 28
- 主要终点
- Best objective intracranial response rate - intent-to-treat
研究概览
简要总结
This is a Prospective Randomized Open Blinded Endpoint phase II clinical trial. The study will be adaptive: an interim analysis is planned after enrolment of 20 patients in each arm of treatment (WBRT and AGuIX® + WBRT), to select and continue the study with group(s) that present the best response rate to the experimental treatment (AGuIX® + WBRT).
The main endpoint will be evaluated by a blinded endpoint committee.
详细描述
The occurrence of brain metastases is a common event in the history of cancer and negatively affects the life expectancy of patients. Their incidence varies between 15 and 50% according to the histologic types. Surgery, stereotactic radiosurgery, radiotherapy and chemotherapy are the main treatments currently proposed.
For patients with multiple brain metastases, whole brain radiation therapy (WBRT) remains the standard of care. However, the median overall survival is less than 6 months and new approaches need to be developed to improve treatment of these patients.
In this context, the weak control of the disease comes from three main factors: the multiplicity of the brain lesions, the radioresistance of certain histologies and the poor distribution of cytotoxic agents in brain metastases.
The use of radiosensitizing agents is here of great interest. The radiosensitizing agent chosen in this study is AGuIX®. It is a Gadolinium-chelated polysiloxane based nanoparticle developed by NH TherAguix company for its theranostic properties (radiosensitization and diagnosis by multimodal imaging). Preclinical studies have demonstrated the radiosensitizing effect of AGuIX® in vivo in 8 tumor models xenografted in rodents, and particularly in brain tumors.
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)
盲法说明
The main endpoint will be evaluated by a blinded endpoint committee.
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
- •Patients with brain metastases, from a histologically confirmed solid tumor, eligible for WBRT
- •At least 18 years old
- •Signed informed consent after informing the patient
- •ECOG (Eastern Cooperative Oncology Group) performance status 0-2
- •Extracranial disease:
- •Complete or partial response or stability under systemic treatment
- •No extracranial disease
- •Or first line of treatment
- •Life expectancy greater than 6 weeks
- •Effective contraceptive method for all patient of childbearing potential
- •Affiliated to a social security regimen
排除标准
- •Leptomeningeal metastasis
- •Evidence of metastasis with recent large hemorrhage
- •Progressive and threatening extracranial disease under systemic treatment
- •Previous cranial irradiation (except stereotactic irradiation)
- •Known contra-indication, sensitivity or allergy to gadolinium
- •Known contra-indication for Magnetic Resonance Imaging
- •Renal insufficiency (glomerular filtration rate ≤ 50 mL/min/1.73m²)
- •Pregnancy or breastfeeding
- •Subject under administrative or judicial control
研究组 & 干预措施
AGuIX® + Whole Brain Radiation Therapy
Intervention: Drug: AGuIX® + WBRT
Other Names:
Gadolinium-chelated polysiloxane based nanoparticles
3 intravenous injections at 100mg/kg
- D0: AGuIX® injection followed by MRI (within 7 days before commencement of WBRT)
- Fr1: AGuIX® injection before the first radiation session
- Fr6: AGuIX® injection before the sixth radiation session
30 Gy in 10 fractions of 3 Gy over 2-3 weeks
干预措施: AGuIX® (Drug)
AGuIX® + Whole Brain Radiation Therapy
Intervention: Drug: AGuIX® + WBRT
Other Names:
Gadolinium-chelated polysiloxane based nanoparticles
3 intravenous injections at 100mg/kg
- D0: AGuIX® injection followed by MRI (within 7 days before commencement of WBRT)
- Fr1: AGuIX® injection before the first radiation session
- Fr6: AGuIX® injection before the sixth radiation session
30 Gy in 10 fractions of 3 Gy over 2-3 weeks
干预措施: Whole Brain Radiation Therapy (Radiation)
Whole Brain Radiation Therapy
Intervention: Radiation: Whole Brain Radiation Therapy ( WBRT) 30 Gy in 10 fractions of 3 Gy over 2-3 weeks
干预措施: Whole Brain Radiation Therapy (Radiation)
结局指标
主要结局
Best objective intracranial response rate - intent-to-treat
时间窗: at 3 months
Evaluation of brain metastases response, according to RECIST v1.1 criteria (or modified RECIST) by MRI, with MRI centralized reading
Best objective intracranial response rate - intent-to-treat
时间窗: at 6 weeks
Evaluation of brain metastases response, according to RECIST v1.1 criteria (or modified RECIST) by MRI, with MRI centralized reading
次要结局
- Evaluation of the quality of life(at day 0, 6 weeks, 3, 6, 9, 12 months)
- Change in steroid dependence(at 6 weeks and 3, 6, 9 and 12 months)
- Best objective intracranial response rate - per-protocol(at 6 weeks and 3 months)
- Evaluation of the intracranial response rate(for 12 months)
- Overall survival(at 12 months)
- Neurocognitive evaluation(at Day 0, 6 weeks, 3, 6, 9, 12 months)
- Intracranial progression-free survival(at 12 months)
- Evaluation of individual metastasis response(at 6 weeks and 3, 6, 9 and 12 months)
- Intracranial progression-free survival, brain survival(at 12 months)
- Incidence of adverse events(at 6 weeks and 3, 6, 9 and 12 months)
- MRI study of the distribution of the product in brain metastases(Day 0)
- Evaluation of the quality of life(at D0, 6 weeks, 3, 6, 9, 12 months)