Non-small cell lung cancer patients who developed acquired resistance to Epidermal Growth Factor Receptor - Tyrosine Kinase Inhibitor (EGFR-TKI) following prior treatment with erlotinib or gefitinib or BIBW 2992 MedDRA version: 14.0 Level: PT Classification code 10061873 Term: Non-small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: BIBW 2992
Product Code: BIBW 2992
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: afatinib
Current Sponsor code: BIBW2992
Concentration unit: mg milligram(s)
Concentration t
Sponsors
Boehringer Ingelheim bv
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Pathologically or cytologically confirmed Stage IIIB/IV disease or recurrent disease following locoregional treatment 2. Either or both of the following: • A tumor which harbors an EGFR-mutation known to be associated with drug sensitivity (i.e., G719X, exon 19 deletion, L858R, L861Q) from previous tumor biopsy or surgery. A tumor which harbors exon 20 insertion or de novo T790M mutation is eligible for the treatment in the sequential arm • Objective clinical benefit from treatment with an EGFR TKI as defined by either 1) Documented partial or complete response (RECIST), or 2) Stable disease =6 months as defined by RECIST in absence of radiographic progression after initiation of gefitinib or erlotinib; or stable disease/PR/CR = 12 weeks as defined by RECIST after initiation of BIBW 2992 3. Systemic progression of disease (RECIST v1.1) while on continuous treatment with erlotinib or gefitinib or BIBW 2992 within the last 30 days. Patients whose disease progresses only in the central nervous system (CNS) are not eligible 4. No intervening systemic therapy between cessation of gefitinib or erlotinib or BIBW 2992 and initiation of the treatment in the study 5. Adequate tumor-derived material such as fresh or archived tumor tissue or pleural fluid from malignant pleural effusion after disease progression on erlotinib/gefitinib/BIBW 2992 must be made available for EGFR mutation analyses 6. Patients aged 18 years or older 7. Life expectancy of at least three (3) months 8. Eastern Cooperative Oncology Group (ECOG) performance score 0-2 9. 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 174 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 66
Exclusion criteria
Exclusion criteria: 1. Prior treatment with EGFR targeting antibodies 2. Prior severe infusion reaction to a monoclonal antibody 3. Major surgery within 28 days or minor surgery within 14 days of the start of the study treatment 4. Radiotherapy less than two weeks prior to the start of the study treatment 5. Systemic chemotherapy, hormonal therapy, immunotherapy, or experimental or approved proteins/antibodies (except erlotinib/gefitinib/BIBW 2992) 2 diarrhea of any etiology 11. History or presence of clinically relevant cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure, New York Heart Association (NYHA) functional classification of 3, unstable angina or poorly controlled arrhythmia. Myocardial infarction within 6 month prior to the study entry 12. Cardiac left ventricular function with resting ejection fraction of less than 50% 13. 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 and anti-tumor activity of the test drug 14. Absolute neutrophil count (ANC) 1.5 times upper limit of normal. Aspartate amino transferase (AST) or alanine amino transferase (ALT) >three times the upper limit of normal (if related to liver metastases >five times the upper limit of normal) 17. Serum creatinine >1.5 times of the upper normal limit or calculated/measured creatinine clearance <60 ml/min 18. Known hepatitis B infection, active hepatitis C infection or known HIV carrier 19. Women of childbearing potential (WOCBP), or men who are able to father a child, unwilling to use a medically acceptable method of contraception during the trial. 20. Pregnancy or breast-feeding 21. Patients unable to comply with the protocol
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To establish the maximum tolerated dose (MTD) and recommended Phase II doses and evaluate the safety and preliminary anti-tumor activity for the combination of BIBW 2992 and cetuximab in patients with non-small cell lung cancer and acquired resistance to erlotinib, gefitinib or BIBW 2992. ;Secondary Objective: Overall safety, pharmacokinetics and anti-tumor activity will be evaluated as secondary objectives. ;Primary end point(s): The primary endpoint is the occurrence of dose limiting toxicity (DLT);Timepoint(s) of evaluation of this end point: The first 28 days of starting the combination therapy during dose-finding phase. DLT occurred at a later timepoint will be assessed separately. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Safety of BIBW 2992 when administered together with cetuximab as indicated by intensity and incidence of adverse events, graded according to NCI CTCAE Version 3.0 2) Pharmacokinetic parameters of BIBW 2992 and cetuximab in the applied treatment setting 3) Objective tumor response (Complete Response [CR] and Partial Response [PR]) determined by RECIST v1.1 4) Disease control (CR, PR and Stable Disease [SD] determined by RECIST v1.1 5) Progression-free survival (PFS) 6) Duration of disease control 7) Duration of objective response ;Timepoint(s) of evaluation of this end point: Patients will continue to be assessed until disease progression or start of new treatment | — |
Countries
Netherlands, United States
Contacts
Public ContactQRPE PSC CT Information Disclosure
Boehringer Ingelheim Pharma GmbH & Co. KG
Outcome results
None listed