A Phase II Open Label, Multicenter Study to Evaluate the Efficacy and Safety of Daily Dose of Lapatinib in Advanced Breast Cancer Patients With HER-2 Non-amplified Primary Tumours and HER-2 Positive Circulating Tumour Cells or EGFR Positive Circulating Tumor Cells
Rationale: Despite recent progress in gene-expression profiling studies, the underlying
biology of the various patterns of metastasis observed in different tumour types remains
unclear. The detection and characterization of circulating tumour cells in cancer patients
has provided important new information about the progression of metastatic events. This
information has important implications for cancer prognosis and therapy.
This open label, multicenter phase II study is designed to evaluate overall tumour response
rate in advanced breast cancer patients with HER-2 non amplified primary tumours with
positive HER-2 or EGFR circulating tumour cells treated with the dual tyrosine kinase
inhibitor GW572016 (Lapatinib).
The patients will be allocated into one of the following two strata:
Stratum 1) Italian study group: Advanced breast cancer patients with HER-2 non-amplified
primary tumours and HER-2 positive circulating tumour cells Stratum 2) UK study group:
Advanced breast cancer patients with HER-2 non-amplified primary tumours and EGFR positive
circulating tumour cells.
All of these patients will be treated with GW572016 (Lapatinib) which targets both HER-2 or
EGFR receptors. A subgroup of patients enrolled into stratum 2 will be asked to participate
in an additional sub-study using Positron Emission Tomography (PET) to quantify the
potential early response to lapatinib treatment.
This study will be a multicenter open-label, phase II study to evaluate the efficacy and
safety of daily dose of Lapatinib in advanced breast cancer patients with HER-2 non
amplified primary tumours and positive HER-2 or EGFR circulating tumour cells.
Patients enrolled in this study will be treated with oral Lapatinib at the dose of 1,500 mg
daily on day 1 to 28 every 4 weeks (q 4 weeks).
Patients will carefully be instructed on drug administration as far as Lapatinib oral intake
is concerned. A daily dose of Lapatinib is six 250 mg tablets taken approximately at the
same time each day. Lapatinib must be taken either at least 1 hour before or after meal.
Dose adjustment, modification and delays are permitted according to procedures described in
the protocol. Initially 16 patients in each stratum will be treated; if 1 to 3 responses are
observed, 15 additional patients will be treated, up to a total of 62 subjects with 31
subjects in each stratum.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
The efficacy of lapatinib in advanced breast cancer patients with HER-2 non-amplified primary tumours with HER-2 or EGFR positive circulating tumour cells.
approx. 6 mos
GSK Clinical Trials
ITALY: Dr. BRUNO CRAVEDI, Direttore Generale dell'Azienda USL 4, Viale della Repubblica, 240, 59100 Prato