A Randomized Phase II Trial of Gefitinib With Anlotinib in Advanced Non-squamous NSCLC Patients With Uncleared Plasma ctDNA EGFRm After First-line Treatment With Gefitinib
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 240
- 试验地点
- 1
- 主要终点
- progression-free survival, PFS
研究概览
简要总结
TKIs therapy is the first-line treatment of patients with EGFR mutation advanced NSCLC.However, some patients have poor prognosis of drug resistance in the early stage. The dynamic alterations of ctDNA-based EGFR mutation after TKIs treatment is a predictor of the efficacy of TKIs treatment, which can be used to identify this part of patients in the early stage.Drug resistance can be overcome when TKIs is combined with drugs in different mechanisms of action, such as chemotherapy and anti-angiogenesis therapy.Gefitinib is the first-generation oral EGFR TKIs. Anlotinib is a domestic oral small molecule inhibitor of multireceptor tyrosine kinase, which has extensive inhibitory effect on tumor angiogenesis and growth.Gefitinib combined with anlotinib is a new option in the treatment of patients with uncleared plasma EGFRm after gefitinib treatment.
详细描述
This is an open-label, prospective, randomized, controlled phase II clinical trial.To evaluate the efficacy and safety of gefitinib combined with anlotinib versus gefitinib alone in advanced non-squamous NSCLC patients whose EGFRm was not cleared in plasma ctDNA after 8 weeks of gefitinib first-line treatment, so as to provide clinical basis for a new and tolerable treatment that can prolong the survival time of patients with advanced NSCLC. Study therapy continued until disease progression, unacceptable adverse event, or withdrawal of consent. The efficacy and adverse reactions of the trial regimen will be evaluated according to RECIST criteria and NCI-CTC AE V3.0.
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
- •Histologically confirmed that EGFR sensitive mutation (ex19del or L858R mutation) in tumor tissue was detected by non-squamous NSCLC, and EGFR mutation (ex19del or L858R mutation) in ctDNA before treatment;
- •Staging is IVB stage (AJCC 8th Edition) ;
- •According to the comprehensive judgment of many disciplines, it is impossible to be treated by operation;
- •PS score 0-1;
- •The patient has at least one measurable tumor injury (the tumor is considered unmeasurable at the site of previous radiotherapy);
- •Systemic anti-tumor therapy such as chemotherapy, immunotherapy and targeted therapy were not performed before entering the group;
- •There is no history of malignant tumor and no serious medical disease;
- •FEV1 ≥ 1.2L/ seconds or ≥ 50% predicted value;
- •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 contraceptive measures during the trial;
- •Life expectancy is more than 12 weeks;
- •Sign informed consent form; cooperate with regular follow-up.
排除标准
- •T4 (AJCC 8th Edition) patients with severe destruction and stenosis of large vessels confirmed by imaging;
- •Clinical severe infection (> grade 2 NCI-CTC V3.0);
- •Severe immunosuppressive disease;
- •The patient's physical condition is life-threatening;
- •A pregnant or breastfeeding patient. Female patients who are likely to become pregnant must be tested negative within 7 days of the start of treatment before continuing. Patients enrolled in the trial (both male and female) must use contraception during the trial period until two weeks after the trial is completed;
- •PS score ≥ 2;
- •At the same time, there are other serious diseases (congestive heart failure, transmural myocardial infarction, COPD or other respiratory diseases that affect treatment, etc.), considering that the study may aggravate or fail to control the disease;
- •Those who have suffered or are currently suffering from tumors whose primary site or histology are different from those evaluated in this study. Excluding cervical carcinoma in situ, cured basal cell carcinoma, bladder surface tumor [Ta,Tis&T1], or any cured tumor that has been in the study for more than 3 years;
- •The patient refused to participate.
研究组 & 干预措施
Gefitinib with Anlotinib
If persistence of plasma ctDNA EGFRm after 8 weeks of gefitinib first-line treatment, Gefitinib 250mg oral daily and Anlotinib 10mg oral d1-14, every 3 weeks
干预措施: Gefitinib (Drug)
Gefitinib with Anlotinib
If persistence of plasma ctDNA EGFRm after 8 weeks of gefitinib first-line treatment, Gefitinib 250mg oral daily and Anlotinib 10mg oral d1-14, every 3 weeks
干预措施: Anlotinib (Drug)
Gefitinib
If clearance of plasma ctDNA EGFRm after 8 weeks of gefitinib first-line treatment, Gefitinib 250mg oral daily
干预措施: Gefitinib (Drug)
结局指标
主要结局
progression-free survival, PFS
时间窗: Every 6 weeks up to 2 years
The period from the start of treatment to the progression or death of a patient
次要结局
- overall survival, OS(Every 6 weeks up to 2 years, and then every 3 months up to 5 years)
- Objective Response Rate, ORR(6 weeks after treatment)
- adverse events(Every 6 weeks up to 2 years)