Stage III, IVa, IVb Squamous Cell Carcinoma of the Head & Neck
Conditions
Interventions
Product Name: Lapatinib
Product Code: GW572016
Pharmaceutical Form: Tablet
INN or Proposed INN: Lapatinib
CAS Number: 388082-78-8
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 or more of the following sites: oral cavity, oropharynx, hypopharynx and larynx; Multiple primary tumours will: •Have to be histologically proven; •Have to be anatomically distant and surrounded by normal tissue; •Exclude distant metastasis. 3) Prior to enrolment subjects must have ErbB1 over-expression determined by immunohistochemistry (IHC) 3+ as assessed by a central laboratory; 4) Subjects with stage III and IVA/IVB disease, who are to receive cisplatin chemotherapy and radiation therapy as primary treatment (total dose 65 - 70 Gy); •Subjects with any Tis, T1 or T2 disease regardless of N stage, are excluded. •Subjects with distant metastases, ie Stage IVC, are excluded. 5) Willing and able to have a tumour biopsy taken at screening; For patients who have had prior tumour biopsy, an adequate archived specimen must be available. 6) Male or female >18 years of age; Criteria for female subjects or female partners of male subjects: Non-child-bearing potential (i.e., women with functioning ovaries who have a current documented tubal ligation or hysterectomy, or women who are post- menopausal); Child-bearing potential (i.e., women with functioning ovaries and no documented impairment of oviductal or uterine function that would cause sterility.) This category includes women with oligomenorrhoea (severe), women who are perimenopausal, and young women who have begun to menstruate. These subjects must have a negative serum pregnancy test at screening and agree to one of the following: •Complete abstinence from intercourse from 2 weeks prior to administration of the first dose of study medication until 28 days after the final dose of study medication; 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; •implants of levonorgestrel; •injectable progestogen; •any intrauterine device (IUD) with a documented failure rate of less than 1% per year; •oral contraceptives (either combined or progestogen only); or •barrier methods, including diaphragm or condom with a spermicide. 7)ECOG performance status 0, 1 or 2; 8)Subjects must have adequate haematological, renal and hepatic function; •Calculated creatinine clearance >50 ml/min as determined by the modified method of Cockcroft and Gault or by the EDTA method. •Absolute neutrophil count >1,500/ul, platelets >100,000/ul. •Haemoglobin >9gm/dL (5mmol/L). •Aspartate (AST) and alanine transaminase (ALT) less than 4 times the upper limit of the normal range (ULN). •Total bilirubin <2.0 mg/dL. 9. Left ventricular ejection fraction (LVEF) within the institutional normal ranges as measured by echocardiogram (ECHO) or Multigated Acquisition (MUGA) scan; 10) Able to swallow tablets whole or swallow a suspension of tablets d
Exclusion criteria
Exclusion criteria: 1) Nasopharyngeal, paranasal sinuses or nasal cavity tumours; 2) Any prior or current treatment for invasive head and neck cancer of any kind. This will include but is not limited to: prior tyrosine kinase inhibitors, prior neoadjuvant therapy, prior surgical resection, or use of any investigational agent; 3) Concurrent use of CYP3A4 inducers or inhibitors. A standard 3-day course of dexamethasone for the prevention of cisplatin-induced nausea and vomiting is permitted; 4) Subjects with known history of uncontrolled or symptomatic angina, arrhythmias, or congestive heart failure; 5) 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; 6) Peripheral neuropathy >grade 2; 7) Pregnant or lactating females (female subjects of child-bearing potential will undertake pregnancy testing at screening and during study completion/withdrawal visits); 8) Malabsorption syndrome, disease significantly affecting GI function, that could affect absorption of lapatinib; 9) History of allergic reactions to appropriate antiemetics (e.g. 5-HT3 antagonists) to be administered with platinum chemotherapy; 10) The investigator considers the subject 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 explore the activity of lapatinib or placebo in the two treatment groups with respect to the complete response rate (per RECIST) at six months (24 weeks) from chemoradiation completion in subjects with locally advanced SCCHN.;Secondary Objective: To evaluate PFS at 6-months and 1-year, OS, disease-specific survival, loco-regional control & distant relapse, evaluate volumetric tumour responses, determine tolerabilty of the proposed regimen, assess serum concentrations of ErbB1, potentially perform proteomic analysis, determination of intra-tumoural expression of ErbB1, ErbB2, ligands for ErbB receptors and downstream biomarkers;Primary end point(s): Complete response rate (per RECIST) at six months (24 weeks) from chemoradiation completion. | — |
Countries
Hungary, Netherlands, Spain, United Kingdom
Outcome results
None listed