A Randomized, Open-label Trial of Gefitinib Versus Combination of Vinorelbine Plus Platinum as Adjuvant Treatment in Pathological Stage II-IIIA(N1-N2) Non-small Cell Lung Cancer With EGFR Mutation
试验速览
- 阶段
- 3 期
- 入组人数
- 222
- 试验地点
- 1
- 主要终点
- Disease free survival
研究概览
简要总结
Activating somatic mutations of the tyrosine kinase domain of epidermal growth factor receptor (EGFR) have been characterized in a subset of patients with advanced NSCLC.The EGFR mutation rate was 30% in Chinese Non-small Cell Lung Cancer(NSCLC). Patients harboring these mutations in their tumors show excellent response to EGFR tyrosine kinase inhibitors (EGFR-TKIs). This randomized phase III trial is studying gefitinib to see how well it works compared to cisplatin-based chemotherapy in treating patients who have undergone surgery for stage II-IIIA(N1-N2) NSCLC with EGFR activating mutation in Asian population.
详细描述
Adjuvant cisplatin-based chemotherapy is recommended for routine use in patients with stages IIA, IIB, and IIIA non-small cell lung cancer (NSCLC) after complete resection. Cisplatin and vinorelbine combination is the standard of care in adjuvant setting. The BR. 19 trial reported adjuvant gefitinib after complete resection of early stage NSCLC(stage IB 49%, II 38%, III 13%) did not confer disease free survival(DFS) or overall survival(OS) advantage in overall population. While the median gefitinib treatment time is only 4.8 months. There are only 76 patients with EGFR mutations included in this analysis. The study closed prematurely in 2005.
Activating somatic mutations of the tyrosine kinase domain of epidermal growth factor receptor (EGFR) have been characterized in a subset of patients with advanced NSCLC.The EGFR mutation rate was 30% in Chinese NSCLC. Patients harboring these mutations in their tumors show excellent response to EGFR tyrosine kinase inhibitors (EGFR-TKIs). This randomized phase III trial is studying gefitinib to see how well it works compared to cisplatin-based chemotherapy in treating patients who have undergone surgery for stage II-IIIA(N1-N2) NSCLC with EGFR activating mutation in Asian population.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written informed consent provided.
- •Males or females aged ≥18 years, < 75 years.
- •Able to comply with the required protocol and follow-up procedures, and able to receive oral medications.
- •Target population is completely resected pathological stage II-IIIA(N1-N2) NSCLC with EGFR exon 19 deletions and exon 21 L858R activating mutation.
- •Patient who can start the investigational therapy within 3-6 weeks after the complete resection
- •ECOG performance status 0-
- •Life expectancy ≥12 weeks.
- •Adequate hematological function: Absolute neutrophil count (ANC) ≥2.0 x 109/L, and Platelet count ≥100 x 109/L, and Hemoglobin ≥9 g/dL (may be transfused to maintain or exceed this level).
- •Adequate liver function: Total bilirubin ≤ 1.5 x upper limit of normal (ULN), Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 2.5 x ULN in subjects without liver metastases; ≤ 5 x ULN in subjects with liver metastases.
- •Adequate renal function: Serum creatinine ≤ 1.25 x ULN, or ≥ 60 ml/min.
- •Female subjects should not be pregnant or breast-feeding.
排除标准
- •Known severe hypersensitivity to gefitinib or any of the excipients of this product.
- •Known severe hypersensitivity to pre-medications required for treatment with cisplatin / vinorelbine doublet chemotherapy.
- •Inability to comply with protocol or study procedures.
- •A serious concomitant systemic disorder that, in the opinion of the investigator, would compromise the patient's ability to complete the study.
- •A serious cardiac condition, such as myocardial infarction within 6 months, angina, or heart disease.
- •Interstitial pneumonia.
- •Patients with prior exposure to agents directed at the HER axis (e.g. erlotinib, gefitinib, cetuximab, trastuzumab).
- •Patients with prior chemotherapy or therapy with systemic anti-tumour therapy (e.g. monoclonal antibody therapy).
- •Patients with prior radiotherapy
- •History of another malignancy in the last 5 years with the exception of the following:Other malignancies cured by surgery alone and having a continuous disease-free interval of 5 years are permitted. Cured basal cell carcinoma of the skin and cured in situ carcinoma of the uterine cervix are permitted.
- •Any unstable systemic disease (including active infection, uncontrolled hypertension, unstable angina, congestive heart failure, myocardial infarction within the previous year, serious cardiac arrhythmia requiring medication, hepatic, renal, or metabolic disease).
- •Eye inflammation or eye infection not fully treated or conditions predisposing the subject to this.
- •Evidence of any other disease, neurological or metabolic dysfunction, physical examination or laboratory finding giving reasonable suspicion of a disease or condition that contraindicated the use of an investigational drug or puts the subject at high risk for treatment-related complications.
- •Patient who has active serious infection (e.g. pyrexia of or 38.0℃ over)
- •Patients who harbouring exon 20 T790M mutation.
研究组 & 干预措施
Gefitinib
Gefitinib 250 mg/day oral daily
干预措施: Gefitinib (Drug)
Vinorelbine+Cisplatin
Vinorelbine 25 mg/m2 intravenous infusion on day 1 and day 8, Cisplatin 75 mg/m2 on day 1 for 4 cycles
干预措施: Vinorelbine+Cisplatin (Drug)
结局指标
主要结局
Disease free survival
时间窗: Pts after surgery will receive long-term follow-up including chest CT scan, abdominal ultrasound every 3 months, brain MRI every 6 months, bone scan every 12 months for up to 3 years. The survival after 3 years will be followed up with telephone.
To evaluate the disease free survival of gefitinib versus combination of vinorelbine plus platinum as adjuvant treatment for pathological stage II-IIIA(N1-N2) NSCLC with EGFR mutation.Disease free survival (DFS)- defined as the time from randomization to the first documented disease progression or death, whichever occurs first.
次要结局
- Overall survival(Pts after surgery will receive long-term follow-up including chest CT scan, abdominal ultrasound every 3 months, brain MRI every 6 months, bone scan every 12 months for up to 3 years. The survival after 3 years will be followed up with telephone.)
- The Total Score and TOI of FACT-L to Measure Quality of life(In the period of Gefitinib 250 mg/day oral daily for 24 months.Vinorelbine 25 mg/m2 intravenous infusion on day 1 and day 8, Cisplatin 75 mg/m2 on day 1 for 4 cycles.)
- Number of Participants with Adverse Events(In the period of Gefitinib 250 mg/day oral daily for 24 months.Vinorelbine 25 mg/m2 intravenous infusion on day 1 and day 8, Cisplatin 75 mg/m2 on day 1 for 4 cycles.)
- 3 yeas DFS rate, 5 years DFS rate, 5 years OS rate(Pts after surgery will receive long-term follow-up including chest CT scan, abdominal ultrasound every 3 months, brain MRI every 6 months, bone scan every 12 months for up to 3 years. The survival after 3 years will be followed up with telephone.)
研究者
Yi-Long Wu
Dr
Guangdong Association of Clinical Trials