An Open-label Phase II Trial of Erlotinib and Bevacizumab in Patients With Advanced Non-small Cell Lung Cancer and Activating EGFR Mutations
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 109
- 试验地点
- 48
- 主要终点
- Progression Free Survival
研究概览
简要总结
Rationale:
Advanced non-small-cell lung cancer (NSCLC) patients harbouring epidermal growth factor receptor (EGFR) mutations (del19 or L858R) show an impressive progression-free survival between 9 and 14 months when treated with erlotinib. However, the presence of EGFR mutations can only imperfectly predict outcome. The investigators hypothesize that progression-free survival could be influenced both by the pretreatment EGFR T790M mutation and by components of DNA repair pathways.
The investigators propose a model of treatment whereby patients with EGFR mutations (single or with T790M) can attain a benefit with longer overall PFS when treated with erlotinib plus bevacizumab. When the patients are grouped by BRCA1 mRNA levels and T790M the hypothesis is that the combination of erlotinib plus bevacizumab can improve the PFS in all subgroups.
详细描述
Objectives:
- To determine long-term outcome of patients with advanced non-squamous NSCLC harbouring EGFR mutations with or without T790M mutation at diagnosis and treated with the combination of erlotinib and bevacizumab. Primary endpoint: progression-free survival
- To evaluate the efficacy and tolerability of the combination
- To evaluate the correlation of BRCA1 mRNA and AEG-1 mRNA expression and T790M with progression-free survival
- To monitor EGFR mutations (including T790M) in serum and plasma longitudinally
- To evaluate molecular biomarkers related to EGFR TKI and bevacizumab
Design:
This is a multinational, multi-center phase II trial of erlotinib plus bevacizumab in patients with advanced non-squamous NSCLC harbouring EGFR mutations confirmed by central re-assessment. Patients will be stratified into two subgroups, with and without EGFR T790M mutation. The stratification will be done after the inclusion of patients.
Sample size: 102 patients
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Age ≥ 18 years
- •ECOG performance status 0-2
- •Adequate haematological function, coagulation, liver function and renal function
- •Pathological diagnosis of predominantly non-squamous, non-small-cell lung cancer (NSCLC)
- •TNM version 7 stage IV disease including M1a (malignant effusion) or M1b (distant metastasis), or locally advanced disease not amenable to curative treatment (including patients progressing after radiochemotherapy for stage III disease)
- •Measurable or evaluable disease (according to RECIST 1.1 criteria).
- •Centrally confirmed EGFR exon 19 deletion (del19) or exon 21 mutation (L858R)
排除标准
- •Patients with increased risk of bleeding
- •Patients with clinically significant cardiovascular diseases
- •Patients with a history of thrombosis or thromboembolism in the 6 months prior to treatment
- •Patients with gastrointestinal problems
- •Patients with neurologic problems
- •Patients who have had in the past 5 years any previous or concomitant malignancy EXCEPT adequately treated basal or squamous cell carcinoma of the skin, in situ carcinoma of the cervix or bladder, in situ breast carcinoma.
- •Patients with any known significant ophthalmologic anomaly of the ocular surface
- •Patients who received prior chemotherapy for metastatic disease
- •Patients who received previous treatment for lung cancer with drugs targeting EGFR or VEGF
- •Pregnancy
研究组 & 干预措施
Erlotinib plus bevacizumab
Patients will be treated with erlotinib and bevacizumab. Bevacizumab: 15 mg/kg i.v. on day 1 of each 3-week cycle (+/- 3 days) Erlotinib: 150 mg p.o., daily
干预措施: Erlotinib (Drug)
Erlotinib plus bevacizumab
Patients will be treated with erlotinib and bevacizumab. Bevacizumab: 15 mg/kg i.v. on day 1 of each 3-week cycle (+/- 3 days) Erlotinib: 150 mg p.o., daily
干预措施: Bevacizumab (Drug)
结局指标
主要结局
Progression Free Survival
时间窗: From the date of enrollment until documented progression or death, whichever occurs first, assessed up to 48 months.
Time from the date of enrollment until an investigator-documented progression or death, whichever occurs first. Assessment of Progressive Disease (PD) is based on Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1): at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum recorded on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
次要结局
- Overall Survival(From the date of enrollment until death, assessed up to 48 months.)
- Disease Control(Assessed across all time-points from enrollment to termination of trial treatment (max 48 months).)
- Time to Treatment Failure(From the date of enrollment until discontinuation of treatment, assessed up to 48 months.)
- Objective Response(Assessed across all time-points from enrollment to termination of trial treatment (max 48 months).)
- Adverse Events(Assessed across all time-points until end of treatment (30 +/-5 days following the last dose of study drug) (max 48 months).)
- Duration of Response(Assessed across all time-points from enrollment to to the date of first documented progression or relapse (max 48 months).)