A Phase IIIb, Non-randomized, Open-label, Two-cohort Study in Patients With EGFR Mutations-positive Advanced Adenocarcinoma of the Lung, Assessing the Utility of the Afatinib Diarrhea Assessment and Management Guidelines (ADAM)
1. Pathologically confirmed diagnosis of Stage IIIB or Stage IV adenocarcinoma of the
lung, with EGFR mutations-positive status, who are not eligible to receive surgery or
chemoradiotherapy. Patients with mixed histology are eligible if adenocarcinoma is
the predominant histology, and is a suitable candidate for EGFR-TKI monotherapy, in
the opinion of the investigator.
2. Patients must have Epidermal Growth Factor Receptor (EGFR) mutation-positive status
according to the institutional standard of care.
3. Patient received no more than one (1) prior chemotherapy for locally advanced or
metastatic adenocarcinoma of the lung.
4. Male or female patients Age 18 years and older.
5. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
6. Adequate organ function, defined as all of the following:
- Left Ventricular Ejection Fraction (LVEF) of above 50% or within institution
- Absolute neutrophil count (ANC) above 1500 / mm3.
- Platelet count above 75,000 / mm3.
- Estimated creatinine clearance more than 45ml / min.
- Total Bilirubin less than 1.5 times upper limit of (institutional/central)
- Aspartate amino transferase (AST) or alanine amino transferase (ALT) less than
three times the upper limit of (institutional/central) normal (ULN) (if related
to liver metastases less than five times ULN).
7. Recovered from any previous therapy related toxicity to Grade 0 or 1 at study entry
8. Able and willing to follow diarrhea management guidelines provided under this study
and to complete Diarrhea Management Worksheet as instructed.
1. Chemotherapy, biological therapy or investigational agents within four weeks prior to
the start of study treatment.
2. Prior treatment with EGFR directed small molecules or antibodies.
3. Hormonal treatment within 2 weeks prior to start of study treatment (continued use of
anti-androgens and/or gonadorelin analogues for treatment of prostate cancer
4. Major surgery within 4 weeks before starting study treatment or scheduled for surgery
during the projected course of the study.
5. Known hypersensitivity to afatinib or the excipients of any of the trial drugs.
6. History or presence of clinically relevant cardiovascular abnormalities.
7. Any history of or concomitant condition that, in the opinion of the Investigator,
would compromise the patient¿s ability to comply with the study or interfere with the
evaluation of the efficacy and safety of the test drug.
8. Previous or concomitant invasive malignancies at other sites.
9. Known pre-existing interstitial lung disease (ILD).
10. Any history or presence of poorly controlled gastrointestinal disorders that could
affect the absorption of the study drug.
14. Active hepatitis B infection, active hepatitis C infection and/or known HIV carrier,
who are determined by the investigator as not a suitable candidate to receive EGFR-TKI
15. Patients with meningeal carcinomatosis. 16. Patients with brain or subdural