Resected Squamous Cell Carcinoma of the Head and Neck MedDRA version: 8.1 Level: LLT Classification code 10041823 Term: Squamous cell carcinoma
Conditions
Interventions
Product Name: Lapatinib
Product Code: GW572016
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Lapatinb
CAS Number: 388082-78-8
Current Sponsor code: GW572016
Other descriptive name: Tyke
Sponsors
GlaxoSmithKline Research & Development Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Willing and able to sign a written informed consent. 2. Histologically confirmed diagnosis of SCCHN of one of the following sites: oral cavity, oropharynx, hypopharynx and larynx. 3. Pathological Stage II, III or IVa with no evidence of gross residual diease, and at least one of the high risk factors by pathology (as listed in protocol) 4. Primary surgery with a curative intent completed within 4-6 weeks (and no later than 8 weeks) prior to randomization. 5. Complete recovery from the surgical procedure. Radiation therapy is required to start as soon as adequate healing has occurred. This is normally around 4-6 weeks but no later than 8 weeks after surgery. 6. Adequate tumour specimen must be available. 7. Subjects must have ErbB1 over-expression in tumour tissue determined by immunohistochemistry (IHC) 3+ as assessed by a central laboratory; 8. Male or female, between 18 and 70 years of age [Bourhis, 2006]. Criteria for female subjects or female partners of male subjects as defined in the protocol 9. ECOG performance status 0, 1 or 2 10. Adequate haematology, renal and hepatic function , as defined in the protocol 11. Left ventricular ejection fraction (LVEF) within 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). 12. Able to swallow and retain tablets whole or swallow a suspension of tablets dissolved in water at study inclusion. 13. Life expectancy of at least 6 months in the best judgement of the investigator Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Nasopharyngeal, paranasal sinuses or nasal cavity tumours 2. Head and neck cancer with histology other than squamous cell. 3. Evidence of distant metastases or gross post-operative residual disease. 4. Any prior or current anticancer treatment of any kind – except the primary surgical resection. This will include but not exclusive to: prior tyrosine kinase inhibitors, prior neoadjuvant therapy, prior radiotherapy or use of any investigational agent. 5. Concurrent use of CYP3A4 inducers or inhibitors while on investigational product. A standard 3-day course of dexamethasone for the prevention of cisplatin induced nausea and vomiting is permitted. 6. Subjects with known history of uncontrolled or symptomatic angina, arrhythmias, or congestive heart failure; 7. Pregnant or lactating females 8. History of another malignancy within the last 5 years, with the exception of completely resected basal or squamous cell skin cancer, or successfully treated in-situ carcinoma. History of non-invasive lesion or in-situ carcinoma, including in the head and neck region that was successfully treated with surgery, photodynamics or laser, will be permitted; 9. Peripheral neuropathy grade 2 10. Mal-absorption syndrome, disease significantly affecting GI function, or major resection of the stomach or bowel, that could affect absorption of lapatinib. 11. History of allergic reactions to relevant diuretics or anti-emetics (e.g. 5-HT3 antagonists) to be administered with cisplatin chemotherapy 12. History of allergic reactions attributed to compounds of similar chemical composition (quinazolines) to lapatinib 13. The investigator considers the patient unfit for the study as a result of the medical interview, physical examinations, or screening investigations
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate and compare DFS from randomisation to the end of the study in high-risk subjects with resected stage III or IVa SCCHN treated with adjuvant placebo or lapatinib and chemoradiotherapy followed by maintenance placebo or lapatinib for 1 year.;Secondary Objective: To evaluate and compare the two treatment arms with respect to: • Overall survival • Disease-specific survival • Time to locoregional recurrence • Time to development of second primary tumour • Time to distant relapse • Qualitative and quantitative toxicities, including late morbidities • Change in quality of life (QoL) status relative to baseline. • Clinical outcome with relevant biomarkers and genetic changes in serum, plasma, and intra-tumoural samples.;Primary end point(s): To evaluate and compare DFS from randomisation to the end of the study in high-risk subjects with resected SCCHN treated with adjuvant placebo or lapatinib for 1 year | — |
Countries
Austria, Czech Republic, Estonia, France, Germany, Greece, Hungary, Ireland, Italy, Latvia, Portugal, Slovakia, United Kingdom
Outcome results
None listed