Recurrent, advanced or metastatic non-small cell lung cancer harbouring activating EGFR mutations with adnocarcinomatous histology MedDRA version: 14.0 Level: LLT Classification code 10025054 Term: Lung cancer non-small cell stage IIIB System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 14.0 Level: LLT Cl
Conditions
Interventions
Product Name: afatinib
Product Code: BIBW 2992
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: afatinib
Current Sponsor cod
Sponsors
Boehringer Ingelheim
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Pathologically confirmed diagnosis of Stage IIIB (not amenable for curative intent local radiotherapy)/IV (recurrent or metastatic) adenocarcinoma of the lung. 2.Documented activating EGFR mutation (Del 19 and/or L858R) with tumour tissues. 3.At least one measurable lesion according to RECIST 1.1 4.Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 5.Age = 18 years. 6.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 •Platelets ?75 x 109/L •Creatinine clearance > 45ml / min. 7.Written informed consent that is consistent with ICH-GCP guidelines. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 200 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 64
Exclusion criteria
Exclusion criteria: 1.Prior systemic chemotherapy for stage IIIB or IV NSCLC. Neo-/adjuvant chemotherapy, chemoradiation or radiotherapy is permitted if at least 12 months has elapsed prior to disease progression, except palliative, limited field radiation to non-target metastatic lesions. 2.Prior treatment with EGFR targeting small molecules or antibodies. 3.Major surgery within 4 weeks of study randomisation. At least 7 days should elapse since minor surgical procedure including placement of an access device or fine needle aspiration and at least 14 days for diagnostic or palliative video-assisted thoracoscopic surgery (VATS) should elapse. 4.Active brain metastases except for the followings: ?- Asymptomatic brain metastases incidentally found during screening process which does not require local treatment in the opinion of the investigator. ?- Asymptomatic brain metastases for which local treatment has been given: At least 1 week off corticosteroids and/or anti-convulsants treatment before study randomisation. 5. Meningeal carcinomatosis. 6.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. 7.Known pre-existing interstitial lung disease. 8.Any history or presence of poorly controlled gastrointestinal disorders that could affect the absorption of the study drug in the opinion of investigator 9.Clinically relevant cardiovascular abnormalities as judged by the investigator 10.Cardiac left ventricular function with resting ejection fraction of less than institutional lower limit of normal (if no lower limit of normal is defined in the institution the lower limit is 50%). 11.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. 12.Pregnancy or breast-feeding. 13.Active hepatitis B infection, active hepatitis C infection and/or known HIV carrier. 14.Use of any investigational drug within 4 weeks of randomisation
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the progression-free survival (PFS) and disease control rate (at 12 months) of afatinib with gefitinib among patients with adenocarcinoma of the lung harbouring activating EGFR mutations who have no prior systemic chemotherapy in advanced setting (stage IIIB or IV);Primary end point(s): Progression-free survival (PFS) and disease control rate at 12 months;Timepoint(s) of evaluation of this end point: After 175 randomized patients have progressed or died or after disease control rate at 12 months is evaluable for all patients, whatever is later.; Secondary Objective: To compare afatinib with gefitinib in terms of: Overall survival (OS), Objective response rate (ORR), Disease control rate (DCR) at 6 and 9 months, Time to objective response, Duration of objective response, Duration of disease control, Tumour shrinkage Time to treatment failure Health-related Quality of Life (HRQoL) and The assessment of safety | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Overall survival (OS), Objective response rate (ORR), Disease control rate (DCR) at 6 and 9 months, Time to objective response, Duration of objective response, Duration of disease control, Tumour shrinkage Time to treatment failure (TTF) Health-related Quality of Life (HRQoL) Intensity and incidence of adverse events, graded according to US NCI CTCAE Version 3.0 ;Timepoint(s) of evaluation of this end point: After "last patient out" the analysis will be performed. | — |
Countries
Australia, Canada, China, France, Germany, Hong Kong, Ireland, Korea, Republic of, Norway, Singapore, Spain, Sweden, Taiwan, United Kingdom
Contacts
Public ContactCML
Boheringer Ingelheim AB
Outcome results
None listed