Ganglioside-Monosialic Acid Prophylaxis for Cognitive Dysfunction Related to Whole Brain Radiotherapy in Breast Cancer Patients With Brain Metastases ，a Multi-center，Randomized，Single Blind，Phase III Clinical Trail
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- 入组人数
- 51
- 试验地点
- 1
- 主要终点
- HVLT R-DR
研究概览
简要总结
To evaluate the efficacy and safety of GM1 for preventing cognitive impairment related to whole brain radiotherapy in breast cancer patients with brain metastases. And explore the clinical and molecular parameter for predicting severe cognitive impairment induced by WBRT and gaining benefit from GM1.
Primary Endpoint: the change of Hopkins Verbal and Learning Test-Revised Delayed Recall,HVLT-R DR,before and after WBRT Secondary ENDPOINT: the change of Alzheimer's Disease Assessment Scale-Cognitive，ADAS-Cog before and after WBRT;severe cognitive impairment percentage and onset time; Design:204 patients will be randomly assigned to exp.group,102 cases,and 102 cases of control group.
详细描述
Background:Brain metastasis is a common event for advanced stage cancer,and whole brain radiotherapy(WBRT)is one of the most effective and widely utilized measures for brain metastases.Gaining control of the brain metastases may provide better survival for patients,but can also cause cognitive impairment,sometimes may be severe.Considering cognitive function is one of the most important aspect of quality of life(QoL), some remedies for the treatment-related adverse effect should be provided. Some agents were evaluated for this purpose,and results were unsatisfying. Ganglioside-Monosialic Acid (GM1) is used as an neuroprotective agent after brain surgery or neurodegenerative disease,and a clinical trail(NCT02468739) hosted by our team demonstrated that it could relief taxane-induced neurotoxicity.So GM1 is proposedto be effective in treating WBRT related cognitive dysfunction.
Outline:This will be an single-blind,randomized study,102 patients planning to receive WBRT will be allocated to control and experiment group,respectively,to receive GM1(100mg D0-D14) or placebo(0.9% saline).Cognitive scales will be utilized to evaluate the efficacy.
PRIMARY OBJECTIVE:
Evaluate the efficacy of GM1 in alleviating WBRT related cognitive impairment by Hopkins Verbal and Learning Test Revised-Delayed Recall(HVLT-R DR) before and after RT.
Secondary Objective:
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 (Participant)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age between 18-75,with histological affirmative breast cancer ,and over 4 brain metastases ,need for WBRT suggested by radiotherapy oncologist ;
- •Estimated survival time over 6months;
- •Abundant hematological function:Absolute Neutrophil Count≥2×109/L ;platelet count≥100×109/L and hemoglobulin≥9 g/dL;
- •Abundant liver function：total bilrubin≤ULN；ASTandALT≤2.5ULN；AKP≤5ULN
- •Can cope with HVLT-RDR and ADAS-Cog evaluation
- •No prior therapy could induce neurological damage,within 4 weeks
- •No more that 1 degree peripheral neuropathy or any other diseases or symptoms that could hinder the evaluation of neurological AE
- •No more treatment or nursing is allowed after enrolling this trail
- •Written Informed Consent signed
排除标准
- •PS score over 2,and estimated no attenuation by WBRT
- •Women with pregnancy or breast feeding
- •Unwilling to contraception measurement
- •Abnormal baseline impairment of cognitive impairment
- •Allergy to experiment agents or components
- •Unsuitable to GM1 treatment, evaluated by investigators
- •Active infection
- •RT dose over 30Gy
研究组 & 干预措施
Experimental arm(GM1)
This arm will be treated with GM1.
干预措施: Monosialotetrahexosyl ganglioside (GM1) (Drug)
Control arm
This arm will be treat with blank placebo.
干预措施: Control (Drug)
结局指标
主要结局
HVLT R-DR
时间窗: 24 weeks after WBRT.
The change of score for Hopkins verbal learning test -revised,delayed recall,form baseline to 24weeks after WBRT,score ranges from 0 to 12,higher score indicates better cognitive function
次要结局
- MMSE(24 weeks after RT.)
- ADAS-Cog(24 weeks after WBRT.)
研究者
Zhong-yu Yuan
Professor
Sun Yat-sen University