Phase II Study Evaluating the Combination of Cetuximab With Afatinib as First-line Treatment for Patients With EGFR Mutated Non Small Cell Lung Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 118
- 试验地点
- 33
- 主要终点
- Time to Treatment Failure
研究概览
简要总结
Until recently, the first line treatment of metastatic Non Small Cell Lung Cancer (NSCLC) was a platine-based chemotherapy. It has been changed by the discovery of EGFR (Epidermal Growth Factor Receptor) mutations and associated treatment with Tyrosine Kinase Inhibitor (TKI) of EGFR. The superiority of EGFR TKI over chemotherapy for EGFR mutated patients has been proved in several phase III trials with gefitinib, erlotinib or afatinib.
Nevertheless, all patients will progress after 9 to 12 months of treatment due to the appearance of a treatment resistance.
Afatinib is an irreversible EGFR TKI. It binds to its receptor permanently.Contrary to erlotinib and gefitinb which inhibits only EGFR, afatinib inhibits the kinase activity of all HER family (Human Epidermal growth factor Receptor). Nevertheless, there is no proof that afatinib delay the appearance of resistance.
Cetuximab is a monoclonal antibody which binds specifically with EGFR. The double inhibition of EGFR by afatinib and cetuximab has demonstrated its efficacy in pre-clinical models. The hypothesis of this study is that the combination between cetuximab and afatinib will permit to delay or decrease the appearance of resistances.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Stage III or IV NSCLC, non irradiable non operable
- •Non squamous NSCLC histologically or cytologically confirmed
- •No previous treatment of NSCLC
- •EGFR mutation (exon 19 deletion, L858R mutation, G719X , L861Q or S768I mutations or exon 19 insertion)
- •Presence of at least one lesion that can be measured
- •PS 0 or 1
排除标准
- •Symptomatic brain metastasis or requiring immediate radiotherapy
- •T790M mutation or exon 20 insertion
- •Radiotherapy less than 2 weeks prior randomization including symptomatic radiotherapy
- •Interstitial pneumopathy
研究组 & 干预措施
Afatinib
Afatinib 40 mg/d until progression
干预措施: Afatinib (Drug)
Afatinib + cetuximab
Afatinib 40 mg/d until progression + cetuximab 500 mg/m² every 2 weeks during 6 months (beginning at D15 at 250 mg/m²)
干预措施: Afatinib (Drug)
Afatinib + cetuximab
Afatinib 40 mg/d until progression + cetuximab 500 mg/m² every 2 weeks during 6 months (beginning at D15 at 250 mg/m²)
干预措施: Cetuximab (Drug)
结局指标
主要结局
Time to Treatment Failure
时间窗: 9 months
次要结局
- Number of participants with treatment-related adverse events as assessed by CTCAE v4.0(1 month)
- Response Rate(9 months)
- Overall survival(12 months)
- Progression-Free Survival(18 months)