Health Condition 1: null- Loco-Regionally advanced Head and Neck Squamous Cell Carcinoma
Conditions
Interventions
Intervention1: Afatinib 20mg,30mg,40mg and 50 mg film coated tablets: Daily Dose - 1 tablet.
Starting dose 40 mg. The dose is escalated to 50 mg and/or reduced to 40 mg, 30 mg, or 20 mg. Continuous
Sponsors
Boehringer Ingelheim Danmark AS
Eligibility
Inclusion criteria
Inclusion criteria: Histologically or cytologically confirmed loco-regionally advanced squamous cell carcinoma stage 3, 4a or 4b of the oral cavity, oropharynx or hypopharynx or larynx stage 4a or 4b Unresected tumour prior to chemoradiotherapy due to Technical unresectability (eg tumour fixation/invasion to either base of the skull, cervical vertebrae, nasopharynx or fixed lymph nodes) and/or Low surgical curability (T3-T4, N2-N3 excluding T1N2) and/or Organ preservation Concomitant platinum-based chemo-radiotherapy completed no longer than 24 weeks prior to randomisation Head and neck radiotherapy, using 3DRT or IMRT, with curative intent to a dose of minimum 66 Gy in 33 fractions (or its radiobiological equivalent) with adequate nodal coverage Cumulative break in radiotherapy for no more than 10 days and At least two cycles of cisplatin (minimum cumulative dose of 200 mg/m2) or carboplatin (minimum cumulative area under the concentration-time curve (AUC) 9) if cisplatin is switched to carboplatin (or vice versa, eg due to intolerance), the following conversion should be used for calculation of minimum cumulative platinum dose: carboplatin 1 AUC equal to cisplatin 22 mg/m2 and At randomisation chemoradiotherapy induced side effects CTCAE grade less than or equal to 2 (exception patients with feeding tube are eligible) No evidence of disease (NED), defined as no measurable or palpable tumour on clinical and radiographic (eg CT scan or MRI) examination as judged by the investigator in either of the following: No residual tumour after CRT No residual tumour after CRT followed by R0 tumour resection No evidence of nodal disease after CRT followed by neck dissection In case of palpable mass, NED must be confirmed by biopsy Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 at the time of randomisation Male and female patients age morethan or equal to 18 years and less than or equal to 70 years Written informed consent that is in compliance with ICH GCP and local law
Exclusion criteria
Exclusion criteria: Patients with smoking history of less than or equal to10 pack years and with primary tumour site base of tongue Patients with smoking history of less than or equal to 10 pack years and with primary tumour site tonsil Primary cancer of nasopharynx, sinuses, and or salivary glands Surgery of the primary tumour or involved lymph nodes ,isolated biopsies or removal of a few lymph nodes are not regarded as surgical procedures, prior to chemoradiotherapy Any other malignancy, except for simultaneous HNSCC primaries, appropriately treated superficial basal cell skin cancer and surgically cured cervical cancer in situ, unless free of disease for at least five years Treatment with any investigational drug or anti cancer therapy less than four weeks prior to randomisation Prior treatment with any EGFR targeted small molecules, EGFR targeted antibodies, and or any investigational agents for treatment of HNSCC Requirement for treatment with any of the prohibited concomitant medications listed in the protocol Known pre existing interstitial lung disease Clinically relevant cardiovascular abnormalities, as judged by the investigator, such as, but not limited to, uncontrolled hypertension, congestive heart failure NYHA classification more than or equal to 3, unstable angina, myocardial infarction within six months prior to randomisation, or poorly controlled arrhythmia Cardiac left ventricular dysfunction with resting ejection fraction of less than institutional lower limit of normal ,if no lower limit of normal is defined in the institution, the lower limit is 50 percent Significant or recent acute gastrointestinal disorders with diarrhoea as a major symptom eg Crohns disease, malabsorption or CTCAE grade greater than 1 diarrhoea of any aetiology at randomisation Known HIV, active hepatitis B and or active hepatitis C, as judged by the investigator Other significant disease that in the investigator opinion would exclude the subject from the trial Screening laboratory values based on central laboratory analysis Absolute neutrophil count (ANC) less than 1and half x109 per litre Platelet count less than 75x109 per litre Total bilirubin greater than 1 and half times the upper limit of normal (ULN) Aspartate amino transferase (AST) or alanine amino transferase (ALT) greater than 3 times the ULN Calculated creatinine clearance less than 50 ml per min 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 two months after end of treatment Adequate methods of contraception and definition of child-bearing potential are described in protocol Pregnancy or breast feeding Known or suspected hypersensitivity to the study medication or the excipients Patients unable to comply with the protocol in the opinion of the investigator Currently involved in another clinical trial interfering with imaging schedules required by this protocol Any past or present history of areca or betel nut chewing or its derivatives for a cumulative duration of more than 3 months
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Disease Free SurvivalTimepoint: Tumour Recurrence or Secondary primary tumour | — |
Secondary
| Measure | Time frame |
|---|---|
| Disease Free Survival Overall Survival Health Related Quality Of Life QuestionnairesTimepoint: Disease Free Survival at 2 years Changes in Health Related Quality of Life Questionnaires relative to baseline | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, Czech Republic, Denmark, Egypt, Finland, France, Germany, Greece, Hungary, India, Ireland, Israel, Italy, Mexico, Netherlands, Peru, Poland, Portugal, Russian Federation, Spain, Sweden, Switzerland, Ukraine, United Kingdom, United States of America
Contacts
Public ContactDr Partha Gokhale
Boehringer Ingelheim India Pvt Ltd
Outcome results
None listed