Study Of Adjuvant Lapatinib In High-Risk Head And Neck Cancer Subjects After Surgery

Inclusion Criteria

• Willing and able to sign a written informed consent.
• Histologically confirmed diagnosis of SCCHN of one of the following sites: oral cavity, oropharynx, hypopharynx and larynx.
• Pathological Stage II, III or IVa (according to AJCC cancer staging criteria [Green, 2002]) with no evidence of gross residual disease, and at least one of the following high risk factors by pathology:
• Extracapsular extension of nodal disease
• Positive resection margin (5 mm or less)
• Primary surgery with a curative intent completed within 4-6 weeks (and no later than 7 weeks) prior to randomization. The extent of surgical resection will follow accepted criteria for adequate excision [Helliwell, 2005]. Surgical margins are divided into 'mucosal' and 'deep', and for each category the resection margin (R) is classified as:
• Clear : (R0) > 5mm.
• Close: (R1) 1 - 5mm.
• Involved: (R2) <1mm
• Complete recovery from the surgical procedure allowing for appropriate radiotherapy. Radiation therapy is required to start as soon as adequate healing has occurred. This is normally around 4-6 weeks but no later than 9 weeks after surgery.
• Adequate tumour specimen from archived or resected tissue must be available for IHC evaluation of ErbB1 expression levels in a central laboratory and subsequent biomarker analysis.
• Male or female, between 18 and 70 years of age [Bourhis, 2006].

Criteria for female subjects or female partners of male subjects:

Non-child-bearing potential (i.e., a woman with functioning ovaries who has a current documented tubal ligation or hysterectomy or a woman who is menopausal); or

Child-bearing potential (i.e. a woman with functioning ovaries and no documented impairment of oviductal or uterine function that would cause sterility. This category includes women with oligomenorrhoea (even severe), women who are perimenopausal and young women who have begun to menstruate), who have a negative serum pregnancy test at screening, and agree to one of the following:

Complete abstinence from intercourse from the time of the screening pregnancy test until 28 days after the final dose of test article; or

Consistent and correct use of one of the following acceptable methods of birth control:

Male partner who is sterile prior to the female subject's entry into the study and is the sole sexual partner for that female subject; or Oral contraceptives (either combined or progestogen only), or Injectable progestogen-only contraceptives or Implants of levonorgestrel, or Any intrauterine device with a documented failure rate of less than 1% per year; or Barrier methods (e.g. condoms, diaphragms, caps) only if used in combination with one of the above acceptable methods.

• ECOG performance status 0, 1 or 2
• Adequate haematology, renal and hepatic function Absolute neutrophil count ≥ 1,500/μL, platelets ≥ 100,000/μL Haemoglobin ≥ 9 gm/dL (5mmol/L) Calculated creatinine clearance ≥60 ml/min as determined by the modified method of Cockcroft and Gault.

Aspartate (AST) and alanine transaminase (ALT) less than 3 times the upper limit of the normal range (ULN).

Total bilirubin ≤ 2.0 mg/dL

• Left ventricular ejection fraction (LVEF) above the lower limits of the institutional normal range as measured by ECHO (if ECHO cannot be performed or if the Investigator feels it is not conclusive to evaluate LVEF, then a MUGA scan should be performed).
• Able to swallow and retain tablets whole or swallow a suspension of tablets dissolved in water at study inclusion.

The use of feeding tube is optional. If necessary, the suspension may be administered via percutaneous endoscopic gastrostomy (PEG), percutaneous jejunostomy tube (J- Tube), or a nasogastric tube (NG or Dobhoff type tube).

• Life expectancy of at least 6 months in the best judgement of the investigator
• Current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, or stable chronic liver disease per investigator asses