A Phase II Study of Primary Tumor Resection for Stage IV Non-small-cell Lung Cancer Without Progression After First-line Epidermal Growth Factor Receptor-tyrosine Kinase Inhibitor
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 100
- 试验地点
- 2
- 主要终点
- 2 year progression free survival rate
研究概览
简要总结
Our project is going to enroll patients with stage IV NSCLC with EGFR mutation and evaluate whether primary tumor resection after receiving the afatinib can prolong survival. This project is supposed to establish a new treatment protocol for stage IV NSCLC with EGFR mutation.
详细描述
In Taiwan, non-small cell lung cancer (NSCLC) has been the leading cause of cancer death, making a phenomenal impact on public health. By understanding the oncogenic driver mutations of NSCLC (e.g. EGFR mutation or ALK rearrangement), the target therapy has taken the place of chemotherapy for its effectiveness and specificity, becoming the new standard of care for stage IV NSCLC. Despite the progress of medical treatment, the majority of patients with stage IV NSCLC still underwent disease progression after a period of time. Noticeably, more than half of the progression was restricted to the original sites of the tumor. It brings up the hypothesis that a combination of local consolidative therapy (e.g. surgery or radial therapy) and medical treatment could be beneficial for these patients. This has been advocated by the latest clinical trials as well.
Our project is going to enroll patients with stage IV NSCLC with EGFR mutation and evaluate whether primary tumor resection after receiving the afatinib can prolong the progression-free survival. This project is supposed to establish a new treatment protocol for stage IV NSCLC with EGFR mutation.
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
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically confirmed non-small cell lung cancer
- •Stage IV non-small cell lung cancer which is amenable to thoracic surgery
- •Patients must have one of the following:NSCLC which harbors EGFR exon 19 deletion or L858R mutation.
- •Eastern Cooperative Oncology Group (ECOG) performance status =< 1
- •Candidate for therapeutic intent surgery to at least one site of disease
- •Signed and dated written informed consent prior to admission to the study in accordance with International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH)-Good Clinical Practice (GCP) guidelines and to the local legislation
排除标准
- •Life expectancy <= 12 weeks
- •With underlying diseases such as moderate to severe Chronic Obstructive Pulmonary Disease or tuberculosis
- •With uncontrol diseases including acute infection, unstable angina or angina in recent 3 months, Heart failure(NYHA≥2), myocardial infarction in recent 6 months, severe arrhythmia, moderate to severe cirrhosis, moderate to severe chronic renal insufficiency, immune insufficiency, any systemic disease with poor prognosis after treatment.
- •With Cerebrovascular Accident complicated dependent activities of daily living.
- •Any other cancer with active treatment in recent 5 years.
- •receive thoracic surgery in the ipsilateral site with the lung cancer previously. （the biopsy surgery required for the diagnosis of lung cancer was not excluded)
- •pregnant or breast-feeding woman
- •Previous treatment with other EGFR TKI. NOTE: Patients who are receiving initial afatinib (6-12 weeks) outside this study are not excluded
- •Disagree to receive Next Generation Sequencing for the lesion specimen after surgery.
研究组 & 干预措施
Group I : Surgery group
The surgery group would receive take 12 weeks of EGFR TKI before randomization. After randomization, the surgery group would receive thoracic surgery with maximal regional control intent. Patients continue afatinib 1 to 2 weeks after surgery until disease progression or unacceptable toxicity. The residual local and metastatic sites of disease could undergo either surveillance or maintenance radio-treatment at the discretion of the treating physician.
干预措施: therapeutic thoracic surgery (Procedure)
Group I : Surgery group
The surgery group would receive take 12 weeks of EGFR TKI before randomization. After randomization, the surgery group would receive thoracic surgery with maximal regional control intent. Patients continue afatinib 1 to 2 weeks after surgery until disease progression or unacceptable toxicity. The residual local and metastatic sites of disease could undergo either surveillance or maintenance radio-treatment at the discretion of the treating physician.
干预措施: Afatinib (Drug)
Group II : Maintenance group
The control group would receive take 12 weeks of EGFR TKI before randomization. After randomization, the control group would receive afatinib until disease progression or unacceptable toxicity. The residual local and metastatic sites of disease could undergo either surveillance or maintenance radio-treatment at the discretion of the treating physician.
干预措施: Afatinib (Drug)
结局指标
主要结局
2 year progression free survival rate
时间窗: start date of afatinib assessed up to 2 years
Will be estimated using Kaplan-Meier method. The stratified log-rank test will be performed to test the difference in time-to-event distributions between treatment groups. Stratified Cox proportional hazards model will be utilized to include multiple covariates in the time-to-event analysis and to estimate hazard ratios.
次要结局
- Progression free survival(From the start date of afatinib assessed up to 4 years)
- Overall survival(From the start date of afatinib assessed up to 4 years)
- Treatment-related adverse events(From the start date of afatinib assessed up to 4 years)
- R0 resection rate(From the start date of afatinib assessed up to 12 weeks)
- resistant mutation events(12 weeks to 4 years)