Clinical trial NCT01121393: BIBW 2992 (Afatinib) vs Gemcitabine-cisplatin in 1st Line Non-small Cell Lung Cancer (NSCLC)
Official title: LUX-Lung 6: A Randomized, Open-label, Phase III Study of BIBW 2992 Versus Chemotherapy as First-line Treatment for Patients With Stage IIIB or IV Adenocarcinoma of the Lung Harbouring an EGFR Activating Mutation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Carcinoma, Non-Small-Cell Lung
Adenocarcinoma
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2010-05-12
Enrollment: 364
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To investigate the efficacy and safety of BIBW 2992 compared to standard first-line chemotherapy in patients with stage IIIB or IV adenocarcinoma of the lung harbouring an EGFR activating mutation


Eligibility criteria: Inclusion criteria:

1. pathologically confirmed diagnosis of stage IIIB or stage IV adenocarcinoma of the Lung
2. EGFR(Epidermal Growth Factor Receptor) mutation detected by central laboratory analysis of tumor biopsy material
3. Measurable disease according to Response Evaluation Criteria in Solid Tumours (RECIST)1.1
4. Eastern Cooperative Oncology Group (ECOG) score of 0 or 1.
5. Age\>=18 years
6. life expectancy of at least three months
7. Written informed consent that is consistent with International Conference on Harmonisation-Good Clinical Practice (ICH-GCP) guidelines.

Exclusion criteria:

1. Prior chemotherapy for relapsed and/or metastatic NSCLC.
2. Prior treatment with EGFR targeting small molecules or antibodies.
3. Radiotherapy or surgery(other than biopsy) within 4 weeks prior to randomization
4. Active brain metastases
5. Any other current malignancy or malignancy diagnosed within the past 5 years
6. Known pre-existing interstitial lung disease
7. Significant or recent acute gastrointestinal disorders with diarrhoea as a a major symptoms.
8. History or presence of clinically relevant cardiovascular abnormalities
9. Cardiac left ventricular function with resting ejection fraction of less than 50%.
10. Any other concomitant serious 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.
11. Absolute neutrophil count(ANC)\<1500/mm3
12. Platelet count\<100,000/mm3
13. Creatinine clearance\<60ml/min or serum creatinine\>1.5 times Upper Limit of Normal (ULN).
14. Bilirubin\>1.5 times ULN
15. Aspartate Amino Transferase (AST) or Alanine Amino Transferase (ALT) \> 3 times ULN
16. Women of childbearing potential, or men who are able to father a child, unwilling to use a medically acceptable method of contraception during the trial
17. Pregnancy of breast-feeding
18. Patients unable to comply with the protocol
19. Active hepatitis B infection, active hepatitis C infection or known HIV(Human Immunodeficiency Virus) carrier.
20. Known or suspected active drug or alcohol abuse.
21. requirement for treatment with any of the prohibited concomitant medications listed in section 4.2.2
22. Any contraindications for therapy with gemcitabine/cisplatin
23. Known hypersensitivity to BIBW2992 or the excipient of any of the trial drugs
24. Use of any investigational drug within 4 weeks of randomization.

Primary outcomes:
measure: Progression-free Survival
timeFrame: Tumour assessment were performed at screening, week 6, 12, 18, 24, 30, 36, 42, 48 and then every 12 weeks until progression or death whichever occurs first up to week 168
Secondary outcomes:
measure: Objective Response (OR)
timeFrame: Tumour assessment were performed at screening, week 6, 12, 18, 24, 30, 36, 42, 48 and then every 12 weeks until progression or death whichever occurs first up to week 374
measure: Disease Control (DC)
timeFrame: Tumour assessment were performed at screening, week 6, 12, 18, 24, 30, 36, 42, 48 and then every 12 weeks until progression or death whichever occurs first up to week 374
measure: Overall Survival (OS)
timeFrame: From randomisation up to 374 weeks
measure: Time to Objective Response (OR)
timeFrame: Tumour assessment were performed at screening, week 6, 12, 18, 24, 30, 36, 42, 48 and then every 12 weeks until progression or death whichever occurs first up to week 374
measure: Duration of Objective Response
timeFrame: Tumour assessment were performed at screening, week 6, 12, 18, 24, 30, 36, 42, 48 and then every 12 weeks until progression or death whichever occurs first up to week 374
measure: Duration of Disease Control
timeFrame: Tumour assessment were performed at screening, week 6, 12, 18, 24, 30, 36, 42, 48 and then every 12 weeks until progression or death whichever occurs first up to week 374
measure: Tumour Shrinkage
timeFrame: Tumour assessment were performed at screening, week 6, 12, 18, 24, 30, 36, 42, 48 and then every 12 weeks until progression or death whichever occurs first up to week 374
measure: Change From Baseline in Body Weight
timeFrame: Baseline and throughout the study (every 3 weeks) until progression or death (whichever occurs first) up to 374 weeks.
measure: Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)
timeFrame: Baseline and throughout the study (every 3 weeks) until progression or death (whichever occurs first) up to 374 weeks.
measure: Health Related Quality of Life (HRQOL): Time of Deterioration in Coughing
timeFrame: Baseline and throughout the study (every 3 weeks) until progression or death (whichever occurs first) up to 374 weeks.
measure: Health Related Quality of Life (HRQOL): Time of Deterioration in Dyspnoea
timeFrame: Baseline and throughout the study (every 3 weeks) until progression or death (whichever occurs first) up to 374 weeks.
measure: Health Related Quality of Life (HRQOL): Time of Deterioration in Pain
timeFrame: Baseline and throughout the study (every 3 weeks) until progression or death (whichever occurs first) up to 374 weeks.
measure: Pharmacokinetics of Afatinib at Day 22
timeFrame: Day 22 (course 2, visit 1)
measure: Pharmacokinetics of Afatinib at Day 29
timeFrame: Day 29 (course 2, visit 2)
measure: Pharmacokinetics of Afatinib at Day 43
timeFrame: Day 43 (course 3, visit 1)
measure: Safety of Afatinib as Indicated by Intensity and Incidence of Adverse Events
timeFrame: From first administration of study medication up to 28 days after the last administration of study medication up to 374 weeks.
measure: Changes in Safety Laboratory Parameters
timeFrame: From first administration of study medication up to 28 days after the last administration of study medication up to 374 weeks.
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Chao-Yang Hospital
city: Beijing
country: China
facility: 307 Hospital of PLA
city: Beijing
country: China
facility: Peking Union Medical College Hospital
city: Beijing
country: China
facility: Beijing Chest Hospital
city: Changchun
country: China
facility: First Hospital of Jilin University
city: Changsha
country: China
facility: Xiangya Hospital, Central South University
city: Changsha
country: China
facility: Hunan Province Tumor Hospital
city: Chengdu
country: China
facility: West China Hospital
city: Fuzhou
country: China
facility: Fujian Provincial Tumor Hospital
city: Guangzhou
country: China
facility: Guangdong General Hospital
city: Guangzhou
country: China
facility: Guangzhou Institute of Respiratory Disease
city: Guangzhou
country: China
facility: NanFang Hosptial
city: Haerbin
country: China
facility: The Third Affiliated Hospital of Harbin Medical University
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
city: HongShan
country: China
facility: Hubei Cancer Hospital
city: Kunming
country: China
facility: Yunnan Provincial Tumor Hospital
city: Linyi
country: China
facility: Lin Yi Tumor Hospital
city: Nan Ning
country: China
facility: The Affiliated Cancer Hospital, Guangxi Medical University
city: Nanjing
country: China
facility: the 81th Hospital of PLA
city: Nanjing
country: China
facility: Jiangsu Cancer Hospital
city: Qingdao
country: China
facility: The affiliated hospital of medicalcollege qingdao university
city: Shanghai
country: China
facility: Shanghai Changzheng Hospital
city: Shanghai
country: China
facility: Shanghai Chest Hospital
city: Shanghai
country: China
facility: Zhongshan Hospital Fudan University
city: Shanghai
country: China
facility: Shanghai Pulmonary Hospital
city: Shanghai
country: China
facility: Changhai Hospital
city: Shenyang
country: China
facility: The First Hospital of Chinese Medical University
city: Shijiazhuang
country: China
facility: Hebei Provincial Tumor Hospital
city: Xi'An
country: China
facility: Tangdu Hospital
city: Yangzhou
country: China
facility: Northern Jiangsu People's Hospital
city: Busan
country: Korea, Republic of
facility: Kosin University Gospel Hospital
city: Cheongju
country: Korea, Republic of
facility: Chungbuk National University Hospital
city: Daegu
country: Korea, Republic of
facility: Yeungnam University Medical Center
city: Seoul
country: Korea, Republic of
facility: Konkuk University Medical Center
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital
city: Songkla
country: Thailand
facility: Songklanagarind Hospital
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
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