Lapatinib Versus Placebo Given Concurrently With Cisplatin And Radiotherapy In Patients With Unresected Head And Neck Cancer
Condition: Neoplasms, Head and Neck
MeSH terms: Head and Neck Neoplasms
Intervention: Lapatinib oral tablets; radiotherapy; cisplatin chemotherapy
Intervention description: Lapatinib is administered orally once daily.; Radiotherapy is given either as conventional fractionation using Two-dimensional (2D) or conformal techniques, or as Intensity Modulated Radiation Therapy (IMRT). Radiation therapy will be standardised throughout the study. Radiation therapy is given only once daily, with a dose/fraction not exceeding 2.5Gy, to a total dose of 65 Gy (IMRT) or 70 Gy (2D or 3D RT) to the gross site of disease .; Cisplatin is administered intravenously at a dose of 100mg/m2 on days 1, 22 and 43 of radiotherapy (approximately Study Days 8, 29 and 50).
Intervention MeSH terms: Lapatinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 67.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Neck Cancer; Locally advanced head and neck cancer; locally advanced; Head and Neck cancer; lapatinib; EGFR/ErbB2 inhibitor; Head Cancer

Summary:

      This is a phase II study comparing the effects of lapatinib versus placebo when administered
      concurrently with cisplatin and radiotherapy followed by 1 year monotherapy with lapatinib or
      placebo. The study is designed to evaluate and compare the two treatment groups with respect
      to complete response rate at 6 months following chemoradiation completion.
    

Eligibility criteria:

        Inclusion criteria:

          -  Willing and able to sign a written informed consent;

          -  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.

          -  Prior to enrolment subjects must have ErbB1 over-expression determined by
             immunohistochemistry (IHC) 3+ as assessed by a central laboratory;

          -  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.

          -  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.

          -  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
        GM2005/00448/00 CONFIDENTIAL EGF105884 22 current documented tubal ligation or
        hysterectomy, or women who are postmenopausal); 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.

          -  ECOG performance status 0, 1 or 2;

          -  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/μl, platelets
             ≥100,000/μl. 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.

          -  Left ventricular ejection fraction (LVEF) within the institutional normal ranges as
             measured by echocardiogram (ECHO) or Multigated Acquisition (MUGA) scan;

          -  Able to swallow tablets whole or swallow a suspension of tablets dissolved in water at
             study inclusion; The use and timing 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 judgment of the investigator.

        Exclusion criteria:

          -  Nasopharyngeal, paranasal sinuses or nasal cavity tumours;

          -  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;

          -  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;

          -  Subjects with known history of uncontrolled or symptomatic angina, arrhythmias, or
             congestive heart failure;

          -  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;

          -  Peripheral neuropathy ≥ grade 2;

          -  Pregnant or lactating females (female subjects of child-bearing potential will
             undertake pregnancy testing at screening and during study completion/withdrawal
             visits);

          -  Malabsorption syndrome, disease significantly affecting GI function, that could affect
             absorption of lapatinib;

          -  History of allergic reactions to appropriate antiemetics (e.g. 5-HT3 antagonists) to
             be administered with platinum chemotherapy;

          -  The investigator considers the subject unfit for the study as a result of the medical
             interview, physical examinations, or screening investigations;