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 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 multicenter open-label study is designed as a two-stage three-outcome phase II trial. The aim is 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 or EGFR positive circulating tumour cells. Evaluation of HER-2 and EGFR status on circulating tumour cells will be performed by the means of the CellSearch equipment (Immunicon, Huntingdon Valley, PA, USA) and FISH method (PathVysion Kit -Abbott Laboratories).

Sex

Female

Minimum age

18 Years

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.

• DERIVEDStebbing J, Payne R, Reise J, Frampton AE, Avery M, Woodley L, Di Leo A, Pestrin M, Krell J, Coombes RC. The efficacy of lapatinib in metastatic breast cancer with HER2 non-amplified primary tumors and EGFR positive circulating tumor cells: a proof-of-concept study. PLoS One. 2013 May 7;8(5):e62543. doi: 10.1371/journal.pone.0062543. Print 2013. PMID 23667487
• DERIVEDPestrin M, Bessi S, Puglisi F, Minisini AM, Masci G, Battelli N, Ravaioli A, Gianni L, Di Marsico R, Tondini C, Gori S, Coombes CR, Stebbing J, Biganzoli L, Buyse M, Di Leo A. Final results of a multicenter phase II clinical trial evaluating the activity of single-agent lapatinib in patients with HER2-negative metastatic breast cancer and HER2-positive circulating tumor cells. A proof-of-concept study. Breast Cancer Res Treat. 2012 Jul;134(1):283-9. doi: 10.1007/s10549-012-2045-1. Epub 2012 Apr 4. PMID 22476856