A Randomized Phase II Trial of Brain Radiotherapy Combined With Targeted Therapy in Patients With Asymptomatic NSCLC Brain Metastasis With Gene Sensitive Mutation
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Intracranial progression-free survival,iPFS-LM
研究概览
简要总结
Brain metastasis is the most common neurological complication in tumor patients, and lung cancer is the most common tumor with brain metastasis. The prognosis of patients with non-small cell lung cancer with brain metastasis is poor. If not treated, the median survival time was about 1 month, the median survival time for steroid therapy was about 2 to 3 months, and the median survival time for patients receiving whole brain radiotherapy was about 3 to 6 months. Studies have shown that the incidence of brain metastasis is not only related to tumor size, N stage and tumor cell type, but also more likely to occur in NSCLC patients with sensitive gene mutation. With the rapid development of NSCLC molecular targeted therapy and precise radiotherapy, the new main therapeutic methods for NSCLC brain metastasis in recent years include stereotactic radiotherapy for (SRT),. Based on intensity modulated technique, simultaneous modulated accelerated radiation therapy for Brain(SMART-Brain) and molecular targeted therapy were carried out. However, at present, the best treatment choice for NSCLC brain metastasis, especially for asymptomatic brain metastasis patients, is still controversial. The choice and combined application mode of individualized treatment for different patients is still a problem to be explored. Based on the synergistic effect of radiotherapy and molecular targeted therapy on the basis of cell and molecule, The purpose of this study was to prospectively compare the efficacy of radiotherapy combined with targeted therapy and targeted therapy alone in patients with asymptomatic NSCLC brain metastasis with gene sensitive mutations, and subgroup analysis of different molecular targets and mutation sites. It is expected that this study will provide a basis for optimizing the curative effect of patients with NSCLC brain metastasis.
详细描述
This is a randomized phase II clinical trial. The objective of the study is to assess efficacy and safety of brain radiotherapy combined with targeted therapy and simple targeted therapy in patients with asymptomatic NSCLC brain metastasis with gene sensitive mutation. Patients were randomized with equal allocation to Molecular targeted therapy alone or with brain radiotherapy. Study therapy continued until disease progression, unacceptable adverse event, or withdrawal of consent
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histology confirmed that it was non-small cell lung cancer;
- •EGFR, ALK or ROS1 gene detection showed sensitive gene mutation, and patients were willing to receive targeted therapy;
- •brain MRI confirmed brain metastasis;
- •asymptomatic or symptomatic brain metastasis could be controlled by glucocorticoid;
- •PS score 0-1;
- •no brain radiotherapy or targeted therapy before entering the group;
- •there was no history of malignant tumor and no serious medical diseases;
- •Laboratory examination: White blood cell count ≥ 4 *10^9/L, neutrophil count ≥ 2.0 *10^9, platelet count ≥ 100 *10^9, hemoglobin ≥ 10 g / L, liver and kidney function and ECG were normal;
- •the pregnancy test was negative within 3 days before entering the group, and agreed to use medically effective contraceptives during the experiment;
- •sign informed consent form.
排除标准
- •Small cell lung cancer was confirmed by pathology;
- •other malignant tumors (unless PFS ≥ 3 years, except non-black skin cancer);
- •were treated with brain radiotherapy or targeted therapy before;
- •those with other potentially serious diseases (congestive heart failure, transmural myocardial infarction, admission with severe acute bacterial or fungal infection, COPD or other respiratory diseases that affect treatment, etc.), Taking into account that the study may exacerbate or fail to control the disease;
- •severe immunosuppressive diseases, such as AIDS;
- •pregnant women, lactating women or women of childbearing age who do not agree with the use of effective contraception in the trial;
- •Intracranial metastasis with obvious symptoms or symptoms that can not be relieved by glucocorticoid alone
研究组 & 干预措施
molecular targeted therapy group
Molecular targeted therapy(according to the results of gene detection, targeted drugs were selected, such as EGFR mutation using the first generation of EGFR-TKI,ALK or ROS1 mutation using the first generation of ALK inhibitors)
干预措施: molecular targeted therapies (Drug)
Brain Radiotherapy and molecular targeted therapy group
Brain Radiotherapy (stereotactic radiotherapy was used for 1-3 intracranial lesions, and simultaneous modulated accelerated radiation therapy for Brain(SMART-Brain )was used for more than 3 intracranial lesions);Molecular targeted therapy(according to the results of gene detection, targeted drugs were selected, such as EGFR mutation using the first generation of EGFR-TKI,ALK or ROS1 mutation using the first generation of ALK inhibitors)
干预措施: molecular targeted therapies (Drug)
Brain Radiotherapy and molecular targeted therapy group
Brain Radiotherapy (stereotactic radiotherapy was used for 1-3 intracranial lesions, and simultaneous modulated accelerated radiation therapy for Brain(SMART-Brain )was used for more than 3 intracranial lesions);Molecular targeted therapy(according to the results of gene detection, targeted drugs were selected, such as EGFR mutation using the first generation of EGFR-TKI,ALK or ROS1 mutation using the first generation of ALK inhibitors)
干预措施: Brain Radiotherapy (Radiation)
结局指标
主要结局
Intracranial progression-free survival,iPFS-LM
时间窗: Every 6 weeks up to 2 years
Time from BM diagnosis to the first documentation of intracranial lesion progression or death with documented intracranial progression
Objective Response Rate,ORR
时间窗: 1 month after treatment
ORR, proportion of patients with a best overall response of complete response or partial response (CR+PR)
次要结局
- Progress Free Survival rate,PFS(Every 6 weeks up to 2 years)
- Median Survival Time,MST(Every 6 weeks up to 2 years)
- adverse events(Every 6 weeks up to 2 years)