lux-head&neck 3: afatinib (bibw2992) versus methotrexate for the treatment of recurrent and/or metastatic head and neck squamous cell cancer after platinum based chemotherapy

Conditions: Head and Neck Neoplasms

Summary: 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.


Eligibility criteria:
inclusion criteria: * histologically or cytologically confirmed squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx or larynx, which has recurred/metastasised and is not amenable for salvage surgery or radiotherapy. * documented progressive disease based on investigator assessment according to recist, following receipt of a cisplatin and/or carboplatin and/or nedaplatin based regimen administered for recurrent and/or metastatic disease independent of whether patient progressed during or after platinum based therapy. * measurable disease according to recist (version 1.1). * eastern cooperative oncology group (ecog) performance status 0 or 1 at visit 2. * male and female patients age is 18 years or older * signed and dated written informed consent that is in compliance with ich-gcp and local law. 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: * 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.