Study of Lapatinib in Breast Cancer Patients With HER-2 Non-amplified Primary Tumors and HER-2 Positive or EGFR Positive Circulating Tumor Cells

• 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. [ Time Frame: approx. 6 mos ] [ Designated as safety issue: No ]
  

• Antitumour activity of lapatinib [ Time Frame: approx. 6 mos ] [ Designated as safety issue: No ]
  
• Safety of lapatinib as measured by number of AEs [ Time Frame: approx. 6 mos ] [ Designated as safety issue: No ]
  
• Early response of lapatinib on proliferation and the MAP kinase cascade by PET in a substudy in patients with EGFR positive CTCs only. [ Time Frame: approx. 6 mos ] [ Designated as safety issue: No ]
  

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.

Study Design:

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.