LUX-Head&Neck 3：Afatinib（BIBW2992）對比 methotrexate 用於鉑類化療後復發及/或轉移性頭頸鱗狀細胞癌的治療

排除條件

• Progressive disease within three months after completion of curatively intended treatment for locoregionally advanced or for metastatic head and neck squamous cell cancer (HNSCC).
• Primary tumour site nasopharynx (of any histology), sinuses, and/or salivary glands.
• Any other than one previous platinum based systemic regimen given for recurrent and/or metastatic disease, with the exception of immunotherapy used either before or after platinum based treatment. Re-challenge with the platinum based regimen after a temporary break is considered an additional line regimen only in case of progression within the break.
• Prior treatment with EGFR-targeted small molecules.
• Treatment with any investigational drug less than four weeks or anti-cancer therapy less than three weeks prior to randomization (except palliative radiotherapy to bones to alleviate pain).
• Unresolved chronic toxicity, other than hearing loss, tinnitus or dry mouth, CTCAE grade \>2 from previous anti-cancer therapy or unresolved skin toxicities CTCAE grade \>1 and/or diarrhoea CTCAE grade \>1 caused by prior treatment with EGFR targeted antibodies.
• Previous tumour bleeding CTCAE grade =3.
• Requirement for treatment with any of the prohibited concomitant medications.
• Major surgical or planned procedure less than four weeks prior to randomization (isolated biopsies are not considered as major surgical procedures).
• Any other malignancy unless free of disease for at least five years except for:
• Other HNSCC of a location as described in inclusion criterion number 1
• Appropriately treated superficial basal cell skin cancer
• Surgically cured cervical cancer in situ
• For Korea: endoscopically cured superficial esophageal and/or gastric cancer is allowed
• Known lesion or signs of brain metastasis.
• Known pre-existing interstitial lung disease (ILD).
• Clinically relevant cardiovascular abnormalities, as judged by the investigator, such as, but not limited to, uncontrolled hypertension, congestive heart failure NYHA classification =III, unstable angina, myocardial infarction within six months prior to randomization, or poorly controlled arrhythmia.
• Significant or recent acute gastrointestinal disorders with diarrhoea as a major symptom in the opinion of the investigator, e.g. Crohn's disease, malabsorption or CTCAE grade \>1 diarrhoea of any aetiology at randomization.
• Known HIV, active hepatitis B, active hepatitis C, and/or other known severe infections, including but not limited to tuberculosis, as judged by the investigator.
• Other significant disease that in the investigator's opinion would exclude the subject from the trial.
• Screening laboratory values:
• Absolute neutrophil count (ANC) \<1.5x10\^9/l
• Platelet count \<75x10\^9/l
• Total bilirubin \>1.5 times the upper limit of normal (ULN)
• Aspartate amino transferase (AST) or alanine amino transferase (ALT) \>3 times the ULN (if related to liver metastases \>5 times the ULN)
• Calculated creatinine clearance \<50 ml/min (as evidenced by using the Cockcroft-Gault formula).
• Women of child-bearing potential and men who are able to father a child, unwilling to be abstinent or to use adequate contraception during the trial and for at least six months after end of treatment. Adequate methods of contraception and definition of child-bearing potential.
• Pregnancy or breast feeding.
• Known or suspected hypersensitivity to any of the study medications or their excipients.
• Patients unable to comply with the protocol, in the opinion of the investigator.