A Study Of Lapatinib Versus Placebo Followed By Chemoradiation In Patients With Locally Advanced Head And Neck Cancer
Condition: Squamous Cell Carcinoma of Head and Neck
MeSH terms: Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck
Intervention: Lapatinib oral tablets; Placebo
Intervention MeSH terms: Lapatinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single
Enrollment: 107.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: squamous cell carcinoma of head and neck; lapatinib; ErbB1/ErbB2 inhibitor; apoptosis

Summary:

      This is a study comparing the activity of lapatinib versus placebo followed by
      chemoradiation. This study is designed to explore the effects of lapatinib monotherapy on
      apoptosis/necrosis, in pre-treatment and post-treatment tumour tissue samples in subjects
      with locally advanced squamous cell carcinoma of head and neck.
    

Eligibility criteria:

        Inclusion criteria:

          -  Willing and able to sign a written informed consent.

          -  Histologically or cytologically confirmed diagnosis of SCCHN.

          -  Stage III, IVA and IVB disease will be eligible, who are to receive chemoradiation
             therapy as primary treatment (total dose ≥ 65 Gy). Subjects with distant metastases
             (stage IVC) will be excluded.

          -  Willing and able to have a tumour biopsy taken at screening and a second tumour biopsy
             taken during lapatinib/placebo administration.

          -  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 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.

          -  Eastern Cooperative Oncology Group (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 method of Cockcroft and Gault
             [Cockcroft, 1976] 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 three 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) scans.

          -  Able to swallow tablet whole or swallow a suspension of the tablet dissolved in water
             at study inclusion. If necessary, the suspension may be administered via percutaneous
             endoscopic gastrostomy (PEG), percutaneous jejunostomy tube (JTube), or a nasogastric
             tube (NG or Dobhoff type tube).

          -  Life expectancy of at least 6 months as judged by the investigator.

        Exclusion criteria:

          -  Subjects with paranasal sinuses, nasopharyngeal and nasal cavity tumours;

          -  Subjects who have received prior systemic chemotherapy given with curative intent;

          -  Subjects who received prior radiotherapy;

          -  Prior or concurrent treatment with tyrosine kinase inhibitors;

          -  Use of any investigational agent within 30 days or 5 half-lives, whichever is longer,
             preceding the first dose of lapatinib;

          -  Concurrent use of CYP3A4 inducers or inhibitors;

          -  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 of head and neck
             that was successfully treated with surgery, photodynamics or laser, will be permitted;

          -  Distant metastases, ie Stage IVC;

          -  Females or males of child-bearing potential who are sexually active, if they do not
             agree to practice an effective method of contraception. (For example oral
             contraceptives, IUD or diaphragm plus spermicide);

          -  Pregnant or lactating females (female patients of childbearing 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 diuretics or antiemetics (e.g. 5-HT3
             antagonists) to be administered with platinum-based chemotherapy;

          -  The investigator considers the patient unfit for the study as a result of the medical
             interview, physical examinations, or screening investigations;

          -  Subjects taking any prohibited medication (See Section 8.2)

        Other Eligibility Criteria Considerations:

        To assess any potential impact on subject eligibility with regard to safety, the
        investigator must refer to the following document(s) for detailed information regarding
        warnings,precautions, contraindications, adverse events, and other significant data
        pertaining to the investigational product(s) being used in this study: investigator's
        brochure IB and any IB supplements, and expedited investigator safety reports