BRMS1 Clinical Trial
Official title:
A Randomized Open-Label, Phase II Study of Lapatinib-capecitabine or Lapatinib-vinorelbine or Lapatinib/Gemcitabine in Subjects With Her2/Neu Amplified Metastatic Breast Cancer Patients Progression After Taxanes Treatment
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.
In areas where trastuzumab is available with no barriers to access, all patients must have
received trastuzumab in the adjuvant or metastatic setting . However, in countries where
trastuzumab is not approved or is not available to patients due to reimbursement or other
considerations, trastuzumab naïve patients are allowed considering the efficacy data of
Lapatinib in this subset of patients.
This trial uses a design to ensure a selection of one or more of the better treatment
combination for additional clinical Approximately (165), who meet the criteria for efficacy
analysis as defined, will be enrolled in the study in a single stage process. The sample
size will be accrued in 16 months, with further follow-up for a 24 months study period from
randomization or until progression.
The study includes a Screening/Baseline Period, a Treatment Period and a post-treatment
Follow-Up Period. Patients will continue to receive investigational products until disease
progression or early discontinuation from investigational product for other reasons.
Patients who discontinue investigational product(s) without disease progression will
continue to be evaluated for efficacy until progression or until receiving the first
subsequent anti-cancer therapy. Once progression is documented, all patients will be
followed for survival at approximately 3-month intervals until death.
;
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment