A Randomised, Open-label, Phase III Study to Evaluate the Efficacy and Safety of Oral Afatinib (BIBW 2992) Versus Intravenous Methotrexate in Patients With Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma Who Have Progressed After Platinum-based Therapy.
A Randomised, Open-label, Phase III Study to Evaluate the Efficacy and Safety of Oral Afatinib (BIBW 2992) Versus Intravenous Methotrexate in Patients With Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma Who Have Progressed After Platinum-based Therapy.
This randomized, open-label, phase III study will be performed in patients with recurrent and/or metastatic head and neck cancer which has progressed after platinum-based therapy. The objectives of this trial are to compare the efficacy and safety of afatinib versus methotrexate.
Inclusion criteria:
Exclusion criteria:
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:
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:
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.
Dakahlia, 35516, Egypt
Muang, 40002, Thailand