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.

1200.161

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.

2013-05-23

2018-08-22

2024-08-31

Active (not recruiting)

Early phase I

340

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.

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE3'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 340, 'type': 'ACTUAL'}}

2024-04-03