A Multicenter Randomized Phase III Study Comparing Second-line Treatment With Chemotherapy Associated or Not to Erlotinib in NSCLC Patients With Secondary Resistance to TKI-EGFR (FLARE)
2017年7月13日 更新者：Centre Francois Baclesse
The current first line treatment of patients with EGFR activating mutation lung cancer is EGFR TKI. Compared to platinum-based chemotherapy, EGFR-TKIs are superior in terms of response rate and progression-free survival. However, an acquired resistance occurs almost constantly. The second-line treatment includes platinum-based chemotherapy in the absence of contraindication. This chemotherapy is then administered after discontinuing EGFR TKIs.
However, a rebound phenomenon of the disease was described in patients who discontinued EGFR TKIs. Some clinical teams therefore recommend, as a precaution, in order to avoid any withdrawal phenomenon, to never discontinue EGFR TKIs in patients developing an EGFR TKI acquired resistance.
It seems therefore useful to conduct a study to better define the therapeutic strategy to adopt in patients developing an acquired resistance after having received EGFR TKIs as first line treatment.
研究概览
地位
终止
研究类型
介入性
注册 (实际的)
6
阶段
- 第三阶段
联系人和位置
本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。
学习地点
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-
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Aix En Provence、法国
- CH
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Amiens、法国
- CH
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Angers、法国、49933
- CHRU
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Annecy、法国、74374
- CH
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Brest、法国、29609
- CHU
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Caen、法国、14000
- Centre François Baclesse
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Creteil、法国、94000
- CHIC
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Draguignan、法国、83007
- CH
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Elbeuf、法国
- CH
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GAP、法国、05007
- CHIC
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La Roche/yon、法国
- Ch La Roche/Yon
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Le MANS、法国、72037
- Centre Hospitalier
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Lille、法国、59020
- Centre Oscar Lambret
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Limoges、法国、87042
- CHU
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Longjumeau、法国、91160
- CH
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Lorient、法国、35632
- CH
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Macon、法国、71018
- CH
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Mantes La Jolie、法国、78201
- CH
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Marseille、法国、13273
- Institut Paoli Calmettes
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Marseille、法国
- AP-HM - Hôpital Nord
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Meaux、法国、77104
- CH
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Meulan、法国、78250
- Centre Hospitalier Intercommunal
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PAU、法国
- CH
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Perpignan、法国
- Centre Catalan
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Rennes、法国、35033
- CHU
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Roanne、法国
- CH
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Rouen、法国
- CHU
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Salon de Provence、法国
- CH
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Sens、法国、89100
- CH
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St BRIEUC、法国
- CH
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St ETIENNE、法国、42271
- Institut de Cancérologie de la Loire
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Strasbourg、法国、67065
- Centre Paul Strauss
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Tarbes、法国
- CH
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Toulon、法国、83041
- Hôpital d'Instruction des Armées Sainte-Anne
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Villefranche、法国、69655
- CH
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参与标准
研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
18年 及以上 (成人、年长者)
接受健康志愿者
不
有资格学习的性别
全部
描述
Inclusion Criteria:
- Man or woman aged 18 years or more
- Non-small cell lung cancer carcinoma (NSCLC) cytologically or histologically confirmed
- Measurable disease according to RECIST 1.1 criteria
- Life expectancy greater than 12 weeks
- Performance Status (ECOG) ≤ 2
- Stage IIIB considered ineligible for thoracic radiotherapy at "curative" doses or stage IV
- Presence of at least one measurable target lesion
- Documented disease progression (RECIST 1.1) after first line treatment with erlotinib, during at least 4 months in case of partial or complete response according to RECIST criteria, or 6 months in case of stable disease. The treatment with Erlotinib should not be discontinued for more than 8 days between the progression and the inclusion in the study. The daily dose of Erlotinib should be at least 50 mg.
- Presence of one of the EGFR activating mutations in the tumor (exon 19 deletion or L858R, G719X or L861Q)
- One additional line of previous chemotherapy is allowed if administered in adjuvant or neoadjuvant setting and received more than six months before.
- Prior radiotherapy is allowed if the volume of irradiated marrow is <25% of the total bone marrow. The prior radiotherapy must be completed at least two weeks before study entry
- Brain metastases are allowed if they are controlled without steroids and if their treatment is completed (radiotherapy and/or surgery). Patients with no symptomatic brain metastases may be included; even if brain metastases are progressive and even if they are the only site of progression (since the investigator considers that irradiation is not required). These metastases have not to be life-threatening (are excluded: cerebellar metastasis ≥ 2 cm, brainstem metastasis, brain metastasis > 3 cm and/or near important functional structure).
- Normal Liver function (bilirubin ≤ULN, AST - ALT ≤2.5 x ULN, alkaline phosphatase ≤3 x ULN), or in case of liver metastases: alkaline phosphatase, AST-ALT ≤ 5 x ULN
- Normal renal function: blood creatinine ≤ULN and / or creatinine clearance> 60 ml/min calculated with the MDRD formula
- Normal blood function: absolute neutrophil count ≥ 1.5 x 109/l and / or platelets ≥ 100 x 109 / l, hemoglobin> 9 g/dl
- Woman and man under efficient contraception during treatment and at least 6 months after the end of treatment by pemetrexed or platinum or gemcitabine
- Signed written Informed consent
Exclusion Criteria:
- Bronchoalveolar, mixed, neuroendocrine and small cell lung cancers
- Patient with only bone metastases are not eligible
- All progressive metastatic sites treated locally (surgery, radiotherapy)
- Superior vena cava syndrome
- Uncontrolled cardiac disease requiring treatment
- Congestive heart failure, angina pectoris, significant arrhythmias or history of myocardial infarction within the previous 12 months
- Neurological or psychiatric disorders
- Uncontrolled infectious disease
- Peripheral neuropathy grade≥ 2
- Definitive contraindication for the use of steroids
- Inductive anti-epileptic treatments (phenobarbital, phenytoïne)• Previous or concomitant other cancer, including skin cancer (except basal cell cancer of the skin), except in situ treated carcinoma of the cervix , except cancer treated with surgery alone without recurrence for 5 years
- Pregnant or breastfeeding woman
- Patient follow-up not achievable
- Participation in a trial within the last 30 days
- Patient deprived of liberty as a result of a justice or administrative decision
学习计划
本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：随机化
- 介入模型：并行分配
- 屏蔽：无（打开标签）
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
|
实验性的：EXPERIMENTAL ARM B
INDUCTION chemotherapy: 4 cycles of
THEN, for responders and for patients with stable disease :MAINTENANCE chemotherapy by Pemetrexed in combination with erlotinib |
|
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有源比较器：STANDARD ARM A
INDUCTION chemotherapy: 4 cycles of
THEN, for responders and for patients with stable disease :MAINTENANCE chemotherapy by Pemetrexed |
研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Efficacy by PFS
大体时间：From date of randomization until the date of first documented progression evaluated every 6-9 weeks
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Efficacy will be assessed by the PFS, define as time between randomization of the patient in the study and disease progression (local, regional, distant and second cancer) or death (all causes).
Alive patients free of progression will be censored at the last follow-up.
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From date of randomization until the date of first documented progression evaluated every 6-9 weeks
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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scores of QoL
大体时间：at 4 months after inclusion
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difference between the scores of QoL at baseline and at 4 months after inclusion for the three targeted dimensions of EORTC QLQ-C30 (global quality of life, fatigue and physical functioning).
A difference or 10 points or more at 4 months after inclusion for one score between the 2 arms will be considered as clinically relevant.
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at 4 months after inclusion
|
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Overall survival
大体时间：From date of randomization until the date of death from any cause, whichever came first, assessed up to 100 months
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Overall survival defined as time interval between randomization and death (all causes).
Alive patients will be censored at the last date of news or data cut off
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From date of randomization until the date of death from any cause, whichever came first, assessed up to 100 months
|
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Tumoral response
大体时间：every 6-9 weeks
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Tumoral response (complete response, partial response, stable disease, progression) according to RECIST 1.1
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every 6-9 weeks
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Toxicities
大体时间：From date of randomization until study participation, assessed up to 100 months
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Toxicities according to NCI-CTC-AE v.4
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From date of randomization until study participation, assessed up to 100 months
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Rebound phenomenon (flare)
大体时间：within 3 weeks after disease progression before inclusion
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Rebound phenomenon (flare) defined by a hospitalization or a death within 3 weeks for disease progression after the end of TKI EGFR treatment (in the arm without EGFR TKI) and date of onset
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within 3 weeks after disease progression before inclusion
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合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
调查人员
- 首席研究员：Radj GERVAIS, MD、Centre François Baclesse - CAEN- FRANCE
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始
2014年6月1日
初级完成 (实际的)
2015年9月1日
研究完成 (实际的)
2015年9月1日
研究注册日期
首次提交
2014年6月25日
首先提交符合 QC 标准的
2014年6月26日
首次发布 (估计)
2014年6月30日
研究记录更新
最后更新发布 (实际的)
2017年7月17日
上次提交的符合 QC 标准的更新
2017年7月13日
最后验证
2016年7月1日
更多信息
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.