Safety Study in Subjects With Metastatic Breast Cancer Who Progressed After Taxanes Treatment.
Status:
Completed
Trial end date:
2011-09-01
Target enrollment:
Participant gender:
Summary
Despite these initial positive signals in recent statistics, breast cancer continues to claim
a substantial number of lives approximately 500,000 deaths worldwide in 2005 Thus the current
treatment paradigm - surgery, radiation and systemic chemo and or hormonal therapy and
biological therapies -still fails to cure a significant number of women with early breast
cancer and new treatment strategies are needed to improve current results both in early and
advance disease.
Recurrent or metastatic breast cancer is an incurable malignancy with a median survival of
20-24 months [Hortobagyi , 1998] and this has not changed significantly over the last decade
with fewer than 20% of patients still alive at 5 years after a diagnosis of recurrence.
Although there have been small improvements in survival with the new therapies, metastatic
breast cancer remains an incurable and, ultimately, fatal disease. The introduction of novel
combination therapies have the potential to target different pathways in the cancer cell,
leading to improved efficacy. Further studies to optimize combination therapy, while
ameliorating AEs, are critically important to patients with metastatic breast cancer.
Lapatinib is an oral tyrosine kinase inhibitor which potently inhibits both EGFR and
HER2[Spector, 2005]. Lapatinib in combination with capecitabine is approved in more than 20
countries for the treatment of patients with advanced or metastatic breast cancer whose
tumors overexpress HER2. All patients in the study leading to the lapatinib approval had
received prior therapy including an anthracycline, a taxane, and trastuzumab.
The relevance of the HER2/neu target in breast cancer, combined with the promising
preclinical and clinical data regarding the use of lapatinib, provide the rationale for a
formal evaluation of this agent combined with other non taxane agents as gemcitabine or
vinorelbine after progression on taxanes and trastuzumab based therapies in metastatic
disease setting as these chemotherapy options are used in daily practice in this subset of
patients.
This is a randomized phase II, open label,multicentric , international, 3 arms treatment
study in patients with confirmed HER2+ metastatic breast cancer after taxane progression .
The main objective is to investigate the (CBR) and safety in 3 different combinations of
Lapatinib therapy (plus capecitabine or gemcitabine or vinorelbine) and to determine whether
either, or both, of Lapatinib /Vinorelbine or Lapatinib/Gemcitabine can be considered a
reasonable alternative to the established Lapatinib/Capecitabine standard combination . The
decision as to whether to study either of the new combinations further will be based on both
the toxicity and the efficacy profiles.