LUX Lung 2 Phase II Single Arm BIBW 2992 "Afatinib" in NSCLC With EGFR Activating Mutations
2016년 7월 28일 업데이트: Boehringer Ingelheim
LUX Lung 2 A Phase II Single-arm Trial of BIBW 2992 in Non-small Cell Lung Cancer Patients With EGFR Activating Mutations
The primary objective of this open-label, single arm Phase II trial is to explore the efficacy of BIBW 2992 defined by the objective response rate (CR, PR) as determined by RECIST criteria in patients with advanced NSCLC Stage IIIB or IV whose tumors harbor activating mutations within exon 18 to exon 21 of the EGFR receptor.
Patients progressing or relapsing after one prior cytotoxic chemotherapy regimen as well as chemotherapy naïve patients (only in stage 2) will be allowed to enter into the trial.
연구 개요
연구 유형
중재적
등록 (실제)
129
단계
- 2 단계
연락처 및 위치
이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.
연구 장소
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Taichung, 대만
- 1200.22.88604 Taichung Veterans General Hospital
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Taichung, 대만
- 1200.22.88605 China Medical University Hospital
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Tainan, 대만
- 1200.22.88606 Boehringer Ingelheim Investigational Site
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Taipei, 대만
- 1200.22.88601 National Taiwan University Hospital
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Taipei, 대만
- 1200.22.88602 Veterans General Hospital
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Taipei City, 대만
- 1200.22.88607 Boehringer Ingelheim Investigational Site
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Taoyuan, 대만
- 1200.22.88603 Chang Gung Memorial Hosp-Linkou
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California
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Bakersfield, California, 미국
- 1200.22.28 Boehringer Ingelheim Investigational Site
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Beverly Hills, California, 미국
- 1200.22.32 Boehringer Ingelheim Investigational Site
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Mission Hills, California, 미국
- 1200.22.4 Boehringer Ingelheim Investigational Site
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Orange, California, 미국
- 1200.22.16 Boehringer Ingelheim Investigational Site
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Florida
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Fort Lauderdale, Florida, 미국
- 1200.22.19 Boehringer Ingelheim Investigational Site
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North Miami Beach, Florida, 미국
- 1200.22.29 Boehringer Ingelheim Investigational Site
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Georgia
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Atlanta, Georgia, 미국
- 1200.22.10 Boehringer Ingelheim Investigational Site
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Illinois
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Chicago, Illinois, 미국
- 1200.22.18 Boehringer Ingelheim Investigational Site
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Maryland
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Bethesda, Maryland, 미국
- 1200.22.3 Boehringer Ingelheim Investigational Site
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Massachusetts
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Boston, Massachusetts, 미국
- 1200.22.14 Boehringer Ingelheim Investigational Site
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Michigan
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Flint, Michigan, 미국
- 1200.22.24 Boehringer Ingelheim Investigational Site
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Minnesota
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Minneapolis, Minnesota, 미국
- 1200.22.5 Boehringer Ingelheim Investigational Site
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New York
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New York, New York, 미국
- 1200.22.15 Boehringer Ingelheim Investigational Site
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New York, New York, 미국
- 1200.22.26 Boehringer Ingelheim Investigational Site
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Rochester, New York, 미국
- 1200.22.1 Boehringer Ingelheim Investigational Site
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Syracuse, New York, 미국
- 1200.22.27 Boehringer Ingelheim Investigational Site
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Valhalla, New York, 미국
- 1200.22.25 Boehringer Ingelheim Investigational Site
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Ohio
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Canton, Ohio, 미국
- 1200.22.6 Boehringer Ingelheim Investigational Site
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Pennsylvania
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Wynnewood, Pennsylvania, 미국
- 1200.22.7 Boehringer Ingelheim Investigational Site
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South Carolina
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Mt. Pleasant, South Carolina, 미국
- 1200.22.22 Boehringer Ingelheim Investigational Site
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Virginia
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Fairfax, Virginia, 미국
- 1200.22.31 Boehringer Ingelheim Investigational Site
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Washington
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Renton, Washington, 미국
- 1200.22.40 Boehringer Ingelheim Investigational Site
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Seattle, Washington, 미국
- 1200.22.33 Boehringer Ingelheim Investigational Site
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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 (성인, 고령자)
건강한 자원 봉사자를 받아들입니다
아니
연구 대상 성별
모두
설명
Inclusion criteria:
- Patients with pathologically confirmed diagnosis of NSCLC Stage IIIB (with pleural effusion) adenocarcinoma or Stage IV adenocarcinoma.
- Presence of activating mutation(s) in exon 18 to exon 21 of the EGFR-receptor confirmed by direct DNA sequencing of NSCLC tumor tissue.
- Progressive disease following a first line cytotoxic chemotherapy regimen or have recurrent disease after prior neoadjuvant or adjuvant chemotherapy. Patients who have not received first-line cytotoxic chemotherapy can be enrolled in stage 2 of the trial, if the criteria for entering stage 2 are met.
- Patients with at least one tumor lesion that can accurately be measured by computed tomography (CT) or magnetic resonance imaging (MRI) in at least one dimension with longest diameter to be recorded as 20 mm using conventional techniques or 10 mm with spiral CT scan.
- Male or female patient aged 18 years.
- Life expectancy of at least three (3) months.
- Written informed consents that is consistent with ICH-GCP guidelines.
- Eastern Cooperative Oncology Group (ECOG) performance score 0, 1 or 2.
Exclusion criteria:
- More than one (1) prior cytotoxic chemotherapy treatment regimen for relapsed or metastatic NSCLC.
- Chemo-, hormone- (other than Megace®) or immunotherapy within the past 4 weeks or within less than four half-lives of the previous drug prior to treatment with the trial drug and/or persistence of toxicities of prior anticancer therapies which are deemed to be clinically relevant.
- Previous treatment with erlotinib (Tarceva®), gefitinib (Iressa®) or any other EGFR inhibiting small molecule or antibody.
- Brain metastases, which are symptomatic; patients with treated, asymptomatic brain metastases are eligible with stable brain disease for at least four (4) weeks without the requirement for steroids or anti-epileptic therapy.
- Significant or recent acute gastrointestinal disorders with diarrhea as a major symptom e.g., Crohns disease, malabsorption, or CTCAE Grade >2 diarrhea of any etiology at baseline.
- Patients who have any other life-threatening illness or organ system dysfunction, which in the opinion of the investigator, would either compromise patient safety or interfere with the evaluation of the safety of the test drug.
- Other malignancies diagnosed within the past five (5) years (other than non-melanomatous skin cancer and in situ cervical cancer).
- Radiotherapy within the past 2 weeks prior to treatment with the trial drug.
- Patients with any serious active infection (i.e., requiring an IV antibiotic, antifungal, or antiviral agents).
- Patients with known HIV, active hepatitis B or active hepatitis C.
- Known or suspected active drug or alcohol abuse.
- Women of child-bearing potential or men who are able to father a child unwilling to use a medically acceptable method of contraception during the trial.
- Pregnancy or breast feeding.
- Patient unable to comply with the protocol.
- History of clinically significant or uncontrolled cardiac disease, including congestive heart failure, angina, myocardial infarction, arrhythmia, including New York Heart Association (NYHA) functional classification of 3.
- Cardiac left ventricular function with resting ejection fraction of less than 50% measured by multigated blood pool imaging of the heart (MUGA scan) or echocardiogram.
- QTc interval greater than 0.47 second.
- Prior treatment with anthracyclines with a cumulative dose of doxorubicin (or equivalent) greater than 400 mg/m2.
- Absolute neutrophil count (ANC) less than 1500/mm3.
- Platelet count less than 100 000 /mm3.
- Bilirubin greater than 1.5 mg / dl (greater than 26 micromol / L, SI unit equivalent).
- Aspartate amino transferase (AST) or alanine amino transferase (ALT) greater than three times the upper limit of normal (if related to liver metastases greater than five times the upper limit of normal).
- Serum creatinine greater than 1.5 times of the upper normal limit or calculated/measured creatinine clearance equal or less than 45 ml / min.
- Patients with known pre-existing interstitial lung disease
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: 해당 없음
- 중재 모델: 단일 그룹 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
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실험적: BIBW 2992
Patients start continuous once daily oral treatment of BIBW 2992 at high dose, until progression or undue Adverse Events (AEs) develop.
Patients can be dose-reduced up to two times if needed after temporary discontinuation of treatment due to drug-related AEs.
After protocol amendment 2 (17 Dec 2008), the starting dose of BIBW 2992 was reduced to a medium dose, with 2 possible dose reductions if needed after discontinuation due to drug-related AEs.
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This is an open label study.
Patients are treated with BIBW 2992 until disease progression or undue AEs
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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Objective Response (OR) as Determined by RECIST 1.0
기간: Response assessment is done at end of Week 4 (after Course 1), Week 8 (after Course 2), Week 12 (after Course 3) and at 8-week intervals thereafter, up to 93 months.
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Objective response (OR) was assessed for all treated patients by independent review as determined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.0.
OR included complete response (CR) and partial response (PR), where CR or PR must have been confirmed by a subsequent response in ≥28 days.
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Response assessment is done at end of Week 4 (after Course 1), Week 8 (after Course 2), Week 12 (after Course 3) and at 8-week intervals thereafter, up to 93 months.
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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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Clinical Benefit as Determined by RECIST 1.0
기간: Response assessment is done at end of Week 4 (after Course 1), Week 8 (after Course 2), Week 12 (after Course 3) and at 8-week intervals thereafter, up to 93 months.
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Clinical benefit was evaluated according to RECIST 1.0 by independent review assessment.
Patients whose best RECIST 1.0 assessment was stable disease (SD), partial response (PR), or complete response (CR) were considered to have derived a clinical benefit from treatment.
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Response assessment is done at end of Week 4 (after Course 1), Week 8 (after Course 2), Week 12 (after Course 3) and at 8-week intervals thereafter, up to 93 months.
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Duration of Clinical Benefit
기간: Response assessment is done at end of Week 4 (after Course 1), Week 8 (after Course 2), Week 12 (after Course 3) and at 8-week intervals thereafter, up to 93 months.
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Duration of clinical benefit (disease control) as per independent review was defined as the time from the start of treatment to the time of progression or death (whichever occurred first), among patients with evidence of SD, PR or CR.
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Response assessment is done at end of Week 4 (after Course 1), Week 8 (after Course 2), Week 12 (after Course 3) and at 8-week intervals thereafter, up to 93 months.
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Duration of Objective Response
기간: Response assessment is done at end of Week 4 (after Course 1), Week 8 (after Course 2), Week 12 (after Course 3) and at 8-week intervals thereafter, up to 93 months.
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Duration of objective response (OR) was measured from the time the criteria for CR or PR (whichever was documented first) were first met until the first date that progressive disease or death (or date of censoring for PFS) was objectively documented as per independent review.
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Response assessment is done at end of Week 4 (after Course 1), Week 8 (after Course 2), Week 12 (after Course 3) and at 8-week intervals thereafter, up to 93 months.
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Time to Objective Response
기간: Response assessment is done at end of Week 4 (after Course 1), Week 8 (after Course 2), Week 12 (after Course 3) and at 8-week intervals thereafter, up to 93 months.
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Time to objective response was defined as the number of days from the start of treatment to the first recorded objective response. Patients who did not experience objective response during the study were censored at the time of treatment discontinuation. The results are provided as the percentage of participants for this Outcome Measure. |
Response assessment is done at end of Week 4 (after Course 1), Week 8 (after Course 2), Week 12 (after Course 3) and at 8-week intervals thereafter, up to 93 months.
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Progression-free Survival
기간: Response assessment is done at end of Week 4 (after Course 1), Week 8 (after Course 2), Week 12 (after Course 3) and at 8-week intervals thereafter, up to 93 months.
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Progression-free survival (PFS) as per independent review was defined as the duration of time from the start of treatment until the day of objective tumor progression was confirmed by tumor imaging (Progressive Disease according to RECIST 1.0) or death, whichever came first.
Patients with unknown progression status or unknown date of progression were reviewed on a case-by-case basis.
Patients known to be alive without progression at the end of the trial or the last follow-up visit were censored at the date of the last imaging when the patient was known to be alive and progression-free.
Medians are calculated from the Kaplan-Meier estimates and 95% confidence intervals, using Greenwood's standard error estimate.
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Response assessment is done at end of Week 4 (after Course 1), Week 8 (after Course 2), Week 12 (after Course 3) and at 8-week intervals thereafter, up to 93 months.
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Overall Survival Time
기간: Start of treatment to time to all death, up to 93 months
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Overall survival time (OS) was also evaluated and was defined as the duration of time from start of treatment to time of death up to 93 months, regardless of the cause of death.
Medians are calculated from the Kaplan-Meier estimates and 95% confidence intervals, using Greenwood's standard error estimate.
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Start of treatment to time to all death, up to 93 months
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Cpre,ss,29
기간: -0:05h (pre-dose) on Day 29
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Predose concentration of the analyte in plasma at steady state immediately before administration of the 29th dose (Cpre,ss,29).
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-0:05h (pre-dose) on Day 29
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Safety of BIBW 2992 as Indicated by Incidence of Specified Adverse Events.
기간: First administration of trial medication until 28 days after last administration of trial medication, up to 93 months.
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Safety of afatinib as indicated by incidence of specified adverse events: skin reactions (a preferred term of the system organ class: Skin and subcutaneous tissue disorders) and gastrointestinal (GI) (a system organ class).
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First administration of trial medication until 28 days after last administration of trial medication, up to 93 months.
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Safety of BIBW 2992 as Indicated by Intensity and Incidence of Worst Adverse Events Graded According to NCI CTCAE Version 3.0
기간: First administration of trial medication until 28 days after last administration of trial medication, up to 93 months.
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Safety of afatinib as indicated by intensity and incidence of worst adverse events graded according to National Cancer Institute (NCI) Common terminology criteria for adverse events (CTCAE) Version 3.0 (R04-0474).
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First administration of trial medication until 28 days after last administration of trial medication, up to 93 months.
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공동 작업자 및 조사자
여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.
간행물 및 유용한 링크
연구에 대한 정보 입력을 담당하는 사람이 자발적으로 이러한 간행물을 제공합니다. 이것은 연구와 관련된 모든 것에 관한 것일 수 있습니다.
일반 간행물
- Yang JC, Sequist LV, Geater SL, Tsai CM, Mok TS, Schuler M, Yamamoto N, Yu CJ, Ou SH, Zhou C, Massey D, Zazulina V, Wu YL. Clinical activity of afatinib in patients with advanced non-small-cell lung cancer harbouring uncommon EGFR mutations: a combined post-hoc analysis of LUX-Lung 2, LUX-Lung 3, and LUX-Lung 6. Lancet Oncol. 2015 Jul;16(7):830-8. doi: 10.1016/S1470-2045(15)00026-1. Epub 2015 Jun 4.
- Yang JC, Shih JY, Su WC, Hsia TC, Tsai CM, Ou SH, Yu CJ, Chang GC, Ho CL, Sequist LV, Dudek AZ, Shahidi M, Cong XJ, Lorence RM, Yang PC, Miller VA. Afatinib for patients with lung adenocarcinoma and epidermal growth factor receptor mutations (LUX-Lung 2): a phase 2 trial. Lancet Oncol. 2012 May;13(5):539-48. doi: 10.1016/S1470-2045(12)70086-4. Epub 2012 Mar 26.
유용한 링크
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
2007년 8월 1일
기본 완료 (실제)
2010년 2월 1일
연구 완료 (실제)
2015년 8월 1일
연구 등록 날짜
최초 제출
2007년 9월 3일
QC 기준을 충족하는 최초 제출
2007년 9월 3일
처음 게시됨 (추정)
2007년 9월 5일
연구 기록 업데이트
마지막 업데이트 게시됨 (추정)
2016년 9월 16일
QC 기준을 충족하는 마지막 업데이트 제출
2016년 7월 28일
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. .
암종, 비소세포폐에 대한 임상 시험
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Taichung Veterans General Hospital완전한심장 독성 | 비소세포폐암 (MeSH 용어: Carcinoma, Non-Small-Cell Lung) | 의약품 관련 부작용 및 이상반응 (MeSH 용어) | Egfr 티로신 키나아제 억제제대만
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Fondazione del Piemonte per l'Oncologia모병유방암 | 난소 암 | 대장암 | 흑색종(피부암) | 비소세포폐암 (MeSH 용어: Carcinoma, Non-Small-Cell Lung)이탈리아
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Millennium Pharmaceuticals, Inc.완전한GCB(Non-Germinal B-cell-like) 미만성 거대 B-세포 림프종(DLBCL)미국
BIBW 2992에 대한 임상 시험
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Boehringer Ingelheim완전한
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Boehringer Ingelheim완전한
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Medical University of South CarolinaBoehringer Ingelheim빼는
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Boehringer Ingelheim완전한
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Boehringer Ingelheim완전한