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
18 Years
N/A
Female
Neoplasms, Breast
Trial Information
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.
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.
Inclusion Criteria:
- Female patients at least 18 years old with HER-2 negative breast cancer.
- Patients must have evidence of HER-2 or EGFR positive circulating tumour cells in a
peripheral blood sample taken at screening visit.
- Patients must have measurable, metastatic disease and no brain metastasis requiring
local therapy.
- Other criteria include ECOG score 0 to 2, life expectancy > 12 weeks, baseline organ
function at screening visit,
- Previous treatment with anthracyclines and/or taxanes in the neo-adjuvant, adjuvant
or advanced setting, and at least one line of treatment for metastatic disease.
Exclusion Criteria:
- Unstable medical conditions, pregnant or lactating women.
- Inability to provide informed consent.
- Lack of physical integrity of the upper gastrointestinal (GI) tract.
- Co-existing malignancy or malignancies within the last 5 years with the exception of
basal cell carcinoma or in-situ carcinoma, concurrent anti-cancer therapies (chemo or
hormonal therapy) or investigational drugs other than study drug.
- Concurrent radiotherapy to the only target lesion or concurrent bisphosphonates if
bone metastases are the only target lesions.
- Previous treatment with anti HER-2 or anti-EGFR therapies.
- Protocol specified treatment regimens that would be inappropriate for the management
of the subject.
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
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.
Outcome Time Frame:
approx. 6 mos
Safety Issue:
No
Principal Investigator
GSK Clinical Trials
Investigator Role:
Study Director
Investigator Affiliation:
GlaxoSmithKline
Authority:
ITALY: Dr. BRUNO CRAVEDI, Direttore Generale dell'Azienda USL 4, Viale della Repubblica, 240, 59100 Prato
Study ID:
105594
NCT ID:
NCT00820924
Start Date:
June 2008
Completion Date:
July 2011
Related Keywords:
- Neoplasms, Breast
- HER-2
- Circulating Tumour Cell (CTC)
- EGFR
- Lapatinib (GW572016)
- Breast Cancer
- Breast Neoplasms
- Neoplasms
- Neoplastic Cells, Circulating
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