Overview

This trial is active, not recruiting.

Conditions carcinoma, non-small-cell lung, adenocarcinoma
Treatments gemcitabine+cisplatin, bibw 2992
Phase phase 3
Targets EGFR, HER2, HER4
Sponsor Boehringer Ingelheim
Start date April 2010
End date December 2013
Trial size 364 participants
Trial identifier NCT01121393, 1200.34

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

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Patients receive a tablet of BIBW 2992 daily until progression or unacceptable toxicity
bibw 2992
starting dose is 40 mg, in the event of no or minimal drug-related adverse events after one course, the dose will be increased to 50mg. in the event of certain drug related AE, dose reduction will be increments of 10 mg, with the lowest dose being 20mg.
(Active Comparator)
Patients receive Gemcitabine and Cisplatin, maximum is 6 courses
gemcitabine+cisplatin
Gemcitabine d1,8, Cisplatin d1, 21 days as a course, up to 6 courses.

Primary Outcomes

Measure
Progression-free Survival
time frame: 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)
time frame: 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
Disease Control (DC)
time frame: 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
Overall Survival (OS)
time frame: From randomisation up to 27 Dec. 2013 cut off date for this analysis
Time to Objective Response (OR)
time frame: 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
Duration of Objective Response
time frame: 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
Duration of Disease Control
time frame: 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
Tumour Shrinkage
time frame: 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
Change From Baseline in Body Weight
time frame: Baseline and throughout the study (every 3 weeks) until progression or death (whichever occurs first) up to 42 months.
Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)
time frame: Baseline and throughout the study (every 3 weeks) until progression or death (whichever occurs first) up to 42 months.
Health Related Quality of Life (HRQOL): Time of Deterioration in Coughing
time frame: Baseline and throughout the study (every 3 weeks) until progression or death (whichever occurs first) up to 42 months.
Health Related Quality of Life (HRQOL): Time of Deterioration in Dyspnoea
time frame: Baseline and throughout the study (every 3 weeks) until progression or death (whichever occurs first) up to 42 months.
Health Related Quality of Life (HRQOL): Time of Deterioration in Pain
time frame: Baseline and throughout the study (every 3 weeks) until progression or death (whichever occurs first) up to 42 months.
Pharmacokinetics of Afatinib at Day 22
time frame: Day 22 (course 2, visit 1)
Pharmacokinetics of Afatinib at Day 29
time frame: Day 29 (course 2, visit 2)
Pharmacokinetics of Afatinib at Day 43
time frame: Day 43 (course 3, visit 1)
Safety of Afatinib as Indicated by Intensity and Incidence of Adverse Events
time frame: From first administration of study medication up to 28 days after the last administration of study medication up to 42.2 months
Changes in Safety Laboratory Parameters
time frame: From first administration of study medication up to 28 days after the last administration of study medication up to 42.2 months

Eligibility Criteria

Male or female participants at least 18 years old.

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 RECIST1.1 4. ECOG(Eastern Cooperative Oncology Group) 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 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 ULN(upper limiter of number). 14. Bilirubin>1.5 times ULN 15. AST(Aspartate Amino Transferase) or ALT(Alanine Amino Transferase) > 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.

Additional Information

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
Trial information was received from ClinicalTrials.gov and was last updated in January 2015.
Information provided to ClinicalTrials.gov by Boehringer Ingelheim.