Study Of Adjuvant Lapatinib In High-Risk Head And Neck Cancer Subjects After Surgery
Condition: Neoplasms, Head and Neck
MeSH terms: Head and Neck Neoplasms
Intervention: Lapatinib; Chemoradiation; Placebo
Intervention description: Dual ErbB1/2 inhibitor; Radiation plus platinum based chemotherapy; Placebo
Intervention MeSH terms: Lapatinib
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 688.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Cancer of the Head and Neck; Neck cancer; Adjuvant; Head and neck cancer; High-risk head and neck cancer; Post-surgery; Head cancer

Summary:

      This is a randomised, double-blind, placebo-controlled, multicentre, global Phase III trial
      comparing the efficacy of adjuvant oral lapatinib versus placebo in high-risk subjects with
      head and neck cancer following surgery. Lapatinib or placebo will be administered
      post-operatively in combination with chemoradiotherapy followed by maintenance with lapatinib
      or placebo for 1 year. The primary goal is to determine if lapatinib is effective at reducing
      the recurrence of the disease in these high-risk patients.
    

Eligibility criteria:

        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
             assessment).

        Exclusion Criteria:

          -  Nasopharyngeal, paranasal sinuses or nasal cavity tumours

          -  Head and neck cancer with histology other than squamous cell carcinoma.

          -  Evidence of distant metastases or gross post-operative residual disease.

          -  Evidence of second primary tumour.

          -  Any prior or current anticancer treatment of any kind - except the primary surgical
             resection. This will include but is not limited to: prior tyrosine kinase inhibitors,
             prior neoadjuvant therapy, prior radiotherapy or use of any investigational agent.

          -  Concurrent treatment with an investigational agent or participation in another
             clinical trial.

          -  Concurrent use of CYP3A4 inducers or inhibitors while on lapatinib/placebo. A standard
             3 to 5 day course of dexamethasone for the prevention of cisplatin induced nausea and
             vomiting is permitted. In addition glucocorticoid daily doses (oral) 1.5mg
             dexamethasone (or equivalent) are allowed.

          -  Subjects with known history of uncontrolled or symptomatic angina, arrhythmias, or
             congestive heart failure;

          -  Pregnant or lactating females

          -  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, that was
             successfully treated with surgery, photodynamics or laser, will be permitted;

          -  Peripheral neuropathy ≥ grade 2

          -  Mal-absorption syndrome, disease significantly affecting GI function, or major
             resection of the stomach or bowel, that could affect absorption of lapatinib.

          -  History of allergic reactions to relevant diuretics or anti-emetics (e.g 5-HT3
             antagonists) to be administered with cisplatin chemotherapy

          -  History of allergic reactions attributed to compounds of similar chemical composition
             (quinazolines) to lapatinib

          -  The investigator considers the subject unfit for the study as a result of the medical
             interview, physical examinations, or screening investigations