Evaluation of efficacy and safety of Afatinib (BIBW 2992) vs. placebo as adjuvant therapy after chemo-radiotherapy in primarily patients with non-surgical intervention with a stage III, IVa or IVb locally advanced Head and Neck squamous cell carcinoma
- Conditions
- Health Condition 1: null- Loco-Regionally advanced Head and Neck Squamous Cell Carcinoma
- Registration Number
- CTRI/2014/02/004416
- Lead Sponsor
- Boehringer Ingelheim Danmark AS
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Other (Terminated)
- Sex
- Not specified
- Target Recruitment
- 669
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
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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Disease Free SurvivalTimepoint: Tumour Recurrence or Secondary primary tumour
- Secondary Outcome Measures
Name Time Method Disease Free Survival <br/ ><br>Overall Survival <br/ ><br> <br/ ><br>Health Related Quality Of Life QuestionnairesTimepoint: Disease Free Survival at 2 years <br/ ><br> <br/ ><br>Changes in Health Related Quality of Life Questionnaires relative to baseline <br/ ><br> <br/ ><br>