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)
2017년 7월 13일 업데이트: 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.
연구 개요
상태
종료됨
연구 유형
중재적
등록 (실제)
6
단계
- 3단계
연락처 및 위치
이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.
연구 장소
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Aix En Provence, 프랑스
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Amiens, 프랑스
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Angers, 프랑스, 49933
- CHRU
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Annecy, 프랑스, 74374
- CH
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Brest, 프랑스, 29609
- CHU
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Caen, 프랑스, 14000
- Centre Francois Baclesse
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Creteil, 프랑스, 94000
- CHIC
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Draguignan, 프랑스, 83007
- CH
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Elbeuf, 프랑스
- CH
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GAP, 프랑스, 05007
- CHIC
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La Roche/yon, 프랑스
- Ch La Roche/Yon
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Le MANS, 프랑스, 72037
- Centre hospitalier
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Lille, 프랑스, 59020
- Centre Oscar Lambret
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Limoges, 프랑스, 87042
- CHU
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Longjumeau, 프랑스, 91160
- CH
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Lorient, 프랑스, 35632
- CH
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Macon, 프랑스, 71018
- CH
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Mantes La Jolie, 프랑스, 78201
- CH
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Marseille, 프랑스, 13273
- Institut Paoli Calmettes
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Marseille, 프랑스
- AP-HM - Hôpital Nord
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Meaux, 프랑스, 77104
- CH
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Meulan, 프랑스, 78250
- Centre Hospitalier Intercommunal
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PAU, 프랑스
- CH
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Perpignan, 프랑스
- Centre Catalan
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Rennes, 프랑스, 35033
- CHU
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Roanne, 프랑스
- CH
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Rouen, 프랑스
- CHU
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Salon de Provence, 프랑스
- CH
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Sens, 프랑스, 89100
- CH
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St BRIEUC, 프랑스
- CH
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St ETIENNE, 프랑스, 42271
- Institut de Cancerologie de La Loire
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Strasbourg, 프랑스, 67065
- Centre Paul Strauss
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Tarbes, 프랑스
- CH
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Toulon, 프랑스, 83041
- Hôpital d'instruction des armées Sainte-Anne
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Villefranche, 프랑스, 69655
- CH
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참여기준
연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.
자격 기준
공부할 수 있는 나이
18년 이상 (성인, 고령자)
건강한 자원 봉사자를 받아들입니다
아니
연구 대상 성별
모두
설명
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
공부 계획
이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
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실험적: 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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활성 비교기: STANDARD ARM A
INDUCTION chemotherapy: 4 cycles of
THEN, for responders and for patients with stable disease :MAINTENANCE chemotherapy by Pemetrexed |
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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Efficacy by PFS
기간: 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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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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scores of QoL
기간: 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
기간: 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
기간: 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
기간: 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)
기간: 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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공동 작업자 및 조사자
여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.
수사관
- 수석 연구원: Radj GERVAIS, MD, Centre François Baclesse - CAEN- FRANCE
연구 기록 날짜
이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.
연구 주요 날짜
연구 시작
2014년 6월 1일
기본 완료 (실제)
2015년 9월 1일
연구 완료 (실제)
2015년 9월 1일
연구 등록 날짜
최초 제출
2014년 6월 25일
QC 기준을 충족하는 최초 제출
2014년 6월 26일
처음 게시됨 (추정)
2014년 6월 30일
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
2017년 7월 17일
QC 기준을 충족하는 마지막 업데이트 제출
2017년 7월 13일
마지막으로 확인됨
2016년 7월 1일
추가 정보
이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .
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