This therapeutic trial is only relevant for patients involved in the TRACERx observational
- Subjects must be willing to have a biopsy of relapsed disease. Consent will be
obtained through the TRACERx study. Procurement of the biopsy sample is not necessary
at the time of trial registration. However, patients must undergo a biopsy prior to
commencement of afatinib.
- Patients must have tumours harbouring a sensitising EGFR mutation or HER2 mutation in
at least one biopsy at recurrence, or region of the primary sample.
- Written Informed consent for DARWIN1.
- ECOG performance status 0-3
- No previous exposure to an EGFR TKI (other than afatinib) or HER2 targeted therapy
- Measurable disease by RECIST v1.1.
- At least 18 years of age.
- Anticipated life expectancy of at least three months.
- Adequate organ function as defined by the following baseline values:
- Absolute neutrophil count (ANC) ≥1.5x109/L
- Platelets ≥100x109/L
- Serum bilirubin ≤1.5 x upper limit of normal (ULN). In patients with known
Gilbert's syndrome, total bilirubin ≤3xULN with direct bilirubin ≤1.5xULN
- Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) ≤3xULN or ≤5x
ULN if liver metastases are present
- Creatinine clearance must be ≥30mL/min
- Women with child-bearing potential, or men who are able to father a child, must be
willing to practice acceptable methods of birth control during the trial and for 1
month after the end of treatment.
- Women of childbearing potential must have a negative pregnancy test within 14 days
before the first dose of trial medication.
- • Suitable for radical radiotherapy.
- Palliative radiotherapy within 2 weeks prior to registration.
- Palliative radiotherapy to a solitary target lesion.
- Requirement for intravenous feeding, active peptic ulcer, prior surgical procedures
affecting absorption or any medical comorbidity affecting gastrointestinal absorption.
- Patients with current or pre-existing interstitial lung disease.
- Significant or recent acute gastrointestinal abnormalities with diarrhoea as a major
symptom e.g. Crohn's disease, malabsorption, or CTCAE v4.03 Grade ≥3 diarrhoea of any
etiology at baseline.
- Known hypersensitivity to afatinib or to any of the excipients.
- Patients with rare hereditary conditions of galactose intolerance, the Lapp lactase
deficiency or glucose-galactose malabsorption
- Anti-cancer therapy including chemotherapy, radiation therapy, immunotherapy, biologic
therapy, or major surgery within 14 days prior to start of trial therapy.
- Known human immunodeficiency virus (HIV), Hepatitis B Virus (HBV), Hepatitis C Virus
(HCV) or syphilis infection. Subjects with evidence of hepatitis B virus clearance may
- History of other malignancy; Exception: (a) Subjects who have been successfully
treated and are disease-free for 3 years, (b) a history of completely resected
non-melanoma skin cancer, (c) successfully treated in situ carcinoma, (d) CLL in
stable remission, or (e) indolent prostate cancer requiring no or only anti-hormonal
therapy with histologically confirmed tumor lesions that can be clearly differentiated
from lung cancer target and non-target lesions are eligible.
- The following cardiac abnormalities:
- Corrected QT (QTc) interval ≥480 msecs
- History of acute coronary syndromes (including unstable angina) within the past
- Coronary angioplasty, or stenting within the past 24 weeks
- Class III, or IV heart failure as defined by the New York Heart Association
(NYHA) functional classification system
- History of known arrhythmias (except sinus arrhythmia) within the past 24 weeks
- Myocardial infarction within the last 6 months
- Uncontrolled medical conditions (i.e., diabetes mellitus, hypertension etc),
psychological, familial, sociological, or geographical conditions that do not permit
compliance with the protocol; or unwillingness or inability to comply with the
requirements of the trial, trial protocol or to provide informed consent.
- Pregnant, lactating or actively breastfeeding females.