LUX-Lung 7: A Phase IIb Trial of Afatinib(BIBW2992) Versus Gefitinib for the Treatment of 1st Line EGFR Mutation Positive Adenocarcinoma of the Lung

Study Overview
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Brief Summary
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This is a randomised, open-label, phase IIb trial of afatinib to compare to gefitinib in first-line treatment setting with patients who are having epidermal growth factor receptor mutation positive advanced adenocarcinoma of the lung.

Official Title
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LUX-Lung 7: A Randomised, Open-label Phase IIb Trial of Afatinib Versus Gefitinib as First-line Treatment of Patients With EGFR Mutation Positive Advanced Adenocarcinoma of the Lung

Conditions
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Lung Neoplasms

Intervention / Treatment
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* Drug: Afatinib
* Drug: gefitinib


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Pathologically confirmed diagnosis of Stage IIIB / IV adenocarcinoma of the lung. Documented activating epidermal growth factor receptor mutation (Del19 and/or L858R) with tumour tissues. At least one measurable lesion according to response evaluation criteria in solid tumours version 1.1 Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. Age >= 18 years. Adequate organ function as defined by the following criteria: Serum aspartate transaminase(AST) and serum alanine transaminase(ALT) =< 3 x upper limit of normal (ULN), or AST and ALT =<5 x ULN if liver function abnormalities are due to underlying malignancy Total serum bilirubin =<1.5 x ULN Absolute neutrophil count (ANC) >=1.5 x 109/L Creatinine clearance > 45ml / min Platelets >= 75 x 109/L Exclusion criteria: Prior systemic chemotherapy for stage IIIB or IV non-small cell lung cancer. Neo-/adjuvant chemotherapy, chemoradiation or radiotherapy is permitted if at least 12 months has elapsed prior to disease progression. Prior treatment with epidermal growth factor receptor targeting small molecules or antibodies. Major surgery within 4 weeks of study randomisation. Active brain metastases Meningeal carcinomatosis. Previous or concomitant malignancies at other sites, except effectively treated non-melanoma skin cancers, carcinoma in situ of the cervix, ductal carcinoma in situ or effectively treated malignancy that has been in remission for more than 3 years and is considered to be cured in the opinion of investigator. Known pre-existing interstitial lung disease. Clinically relevant cardiovascular abnormalities as judged by the investigator. Cardiac left ventricular function with resting ejection fraction of less than institutional lower limit of normal. Women of child-bearing potential (WOCBP) and men who are able to father a child, unwilling to be abstinent or use adequate contraception prior to study entry, for the duration of study participation and for at least 2 months after treatment has ended. Pregnancy or breast-feeding. Active hepatitis and/or known HIV carrier Any prohibited concomitant medications for therapy with afatinib or gefitinib

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: afatinib<br>afatinib once daily. | Drug: Afatinib<br>* afatinib once daily<br>* Other names: Giotrif® / Gilotrif®;|
| Active Comparator: gefitinib<br>gefitinib once daily | Drug: gefitinib<br>* Gefitinib once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival | Progression-free survival (PFS) defined as the time from date of randomisation to date of disease progression, or date of death if a patient died earlier. Participants with no event (Disease progression (PD) or death) were censored. PD was primarily evaluated for the primary analysis by an independent central imaging review according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. Per RECIST version 1.1. for target lesions and assessed by Computed Tomography (CT)-scan or Magnetic Resonance Imaging (MRI): PD, At least a 20% increase in the sum of the longest diameter (SoD) of target lesions taking as reference the smallest SoD of target lesions recorded since the treatment started, together with an absolute increase in the SoD of target lesions of at least 5 millimetre (mm) or the appearance of one or more new lesions. For the final analysis (analysis cut-off date 12 April 2019) status and date of PD were determined by investigator assessment. | From first drug administration until 28 days after last drug administration + Follow-Up period for collecting information on disease progression or death, up to 2465 days. | 
| Time to Treatment Failure (TTF) (Main Overall Survival Analysis Cut-off Date, 08 April 2016) | Time to Treatment Failure (TTF) which was the time from the date of randomisation to the date of i.e. permanent treatment discontinuation for any reason. | From first drug administration until last drug administration, up to 1482 days | 
| Overall Survival | Overall survival (OS) which was defined as the time from the date of randomisation to the date of death. Participants for whom there is no evidence of death at the time of the analysis will be censored at the date that they were last known to be alive. | From first drug administration until 28 days after last drug administration + Follow-Up period for collecting information on death, up to 2465 days. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate | Objective response rate (ORR) which was defined as the number of participants with best overall response of complete response (CR) or partial response (PR) as assessed by central independent review according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. divided by the total number of participants who received treatment. Per RECIST version 1.1. for target lesions and assessed by Computed Tomography (CT)-scan or Magnetic Resonance Imaging (MRI): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions from baseline. For the final analysis (analysis cut-off date 12 April 2019) objective response was determined by investigator assessment. | From first drug administration until 28 days after last drug administration + Follow-Up period for collecting information on disease progression, further anti-cancer treatment and death, up to 2465 days. | 
| Time to Objective Response | Number of participants with objective response (best overall response of complete response or partial response) to study treatment over time, cumulative number of participants is displayed. Time to objective response was defined as the time from randomisation to the first recorded objective response. For the final analysis (analysis cut-off date 12 April 2019) objective response was determined by investigator assessment. | From first drug administration until 28 days after last drug administration + Follow-Up period for collecting information on disease progression, further anti-cancer treatment and death, up to 2465 days. | 
| Duration of Objective Response | Duration of objective response defined as the time of first objective response (best overall response of complete response or partial response) to the time of progression or death, whichever occurred first (or date of censoring for progression free survival). For the final analysis (analysis cut-off date 12 April 2019) objective response was determined by investigator assessment. | From first drug administration until 28 days after last drug administration + Follow-Up period for collecting information on disease progression, further anti-cancer treatment and death, up to 2465 days. | 
| Disease Control | Percentage of participants with disease control which was defined as the number of participants with best overall response of complete response (CR) or partial response (PR) or stable disease (SD) as assessed by central independent review according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. divided by the total number of participants who received treatment. Per RECIST version 1.1. for target lesions and assessed by Computed Tomography (CT)-scan or Magnetic Resonance Imaging (MRI): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions from baseline; Stable Disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Responses of SD were only considered if they occur ≥42 days from date of randomisation. For the final analysis (analysis cut-off date 12 April 2019) disease control was determined by investigator assessment. | From first drug administration until 28 days after last drug administration + Follow-Up period for collecting information on disease progression or death, up to 2465 days. | 
| Duration of Disease Control | Duration of disease control defined as the time from randomisation to the time of progression or death, whichever occurred first (or date of censoring for progression free survival). For the final analysis (analysis cut-off date 12 April 2019) the status and date of disease progression were determined by investigator assessment. | From first drug administration until 28 days after last drug administration + Follow-Up period for collecting information on disease progression or death, up to 2465 days. | 
| Tumour Shrinkage (Main Overall Survival Analysis Cut-off Date, 08 April 2016) | Tumour shrinkage assessed by minimum sum of post-baseline target lesion diameters recorded after randomisation. A positive value shows a decrease in tumour size. | From first drug administration until last drug administration, up to 1482 days | 
| Health-related Quality of Life (Primary Analysis Cut-off Date, 21 August 2015) | Health-related quality of life (HRQoL) measured using European Quality of life - 5 Dimensions (EQ-5D) score for United Kingdom (UK) and Belgium and European European Quality Visual Analogue Scale (EQ-VAS). EQ-5D utility scores range from 0 (worst health) to 1 (full health). EQ-VAS scores range from 0 (worst imaginable health state) to 100 (best imaginable health state). Results display the mean score up to 56 weeks. | Every 8 weeks, up to 56 weeks |