Safety Study in Subjects With Metastatic Breast Cancer Who Progressed After Taxanes Treatment.

2014-08-27 03:16:38 | BioPortfolio


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.

Study Design

Allocation: Randomized, Control: Active Control, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment




Lapatinib Vinorelbine, Lapatinib Capecitabine, Gemcitabine Lapatinib


Dr. Carlos Alberto Sampaio




Grupo Latino Americano de Investigacoes Cli­nicas em Oncologia

Results (where available)

View Results


Published on BioPortfolio: 2014-08-27T03:16:38-0400

Clinical Trials [1762 Associated Clinical Trials listed on BioPortfolio]

Lapatinib in Combination With Vinorelbine

This is a randomized, parallel-arm, open-label, multi-centre, Phase II study to determine the efficacy and safety of lapatinib in combination with vinorelbine or capecitabine in women with...

APRiCOT-B: Study to Evaluate Apricoxib in Combination With Lapatinib and Capecitabine in the Treatment of HER2/Neu+ Breast Cancer (TP2001-202)

This study will compare the anti-tumor efficacy of apricoxib and lapatinib/capecitabine with placebo and lapatinib/capecitabine as measured by time to disease progression and evaluate urin...

Rollover Study Of Lapatinib In Cancer Patients

The EGF19060 study is a rollover study to evaluate the long term safety of lapatinib and to provide lapatinib to patients who had a positive response in previous lapatinib studies until la...

Study For Patients With Untreated Gastric Cancer Who Will Receive Capecitabine And Lapatinib

The study will determine if changes in expression of markers involved in the 5-FU pathways are associated with response to treatment with the combination of lapatinib and capecitabine inde...

Lapatinib in Combination With Vinorelbine

This is a Multicenter, Open-Label, Phase II Study of Lapatinib in Combination with Vinorelbine in women with documented evidence of HER2/neu positive breast cancer which is metastatic or r...

PubMed Articles [185 Associated PubMed Articles listed on BioPortfolio]

A sensitive LC-MS-MS assay for the determination of lapatinib in human plasma in subjects with end-stage renal disease receiving hemodialysis.

Most bioanalytical methods reported in literature for the quantitation of lapatinib in human plasma are either for lapatinib alone or lapatinib administered along with other tyrosine kinase inhibitors...

Phosphoproteomic analysis reveals PAK2 as a therapeutic target for lapatinib resistance in HER2-positive breast cancer cells.

The human epidermal growth factor receptor 2 (HER2)-positive breast cancer with overexpression of HER2 accounts for approximately 25% of breast cancers and is more aggressive than other types of breas...

Lapatinib, a Dual Inhibitor of Epidermal Growth Factor Receptor (EGFR) and HER-2, Enhances Radiosensitivity in Mouse Bladder Tumor Line-2 (MBT-2) Cells In Vitro and In Vivo.

BACKGROUND The aim of this study was to evaluate the effect of lapatinib, a dual inhibitor of epidermal growth factor receptor (EGFR) and HER-2, on the radiosensitivity of murine bladder tumor line-2 ...

Design and development of PEGylated liposomal formulation of HER2 blocker Lapatinib for enhanced anticancer activity and diminshed cardiotoxicity.

Breast cancer is most frequently diagnosed cancer and fifth leading cause of death in women. About 20-30% of all breast cancers overexpress HER2/neu receptors. Lapatinib is a dual tyrosin kinase inhib...

Effect of lapatinib on meningioma growth in adults with neurofibromatosis type 2.

Epidermal growth factor receptors EGFR and ErbB2 are overexpressed in schwannomas and meningiomas. Preclinical and clinical data indicate that lapatinib, an EGFR/ErbB2 inhibitor, has antitumor activit...

Medical and Biotech [MESH] Definitions

A deoxycytidine derivative and fluorouracil PRODRUG that is used as an ANTINEOPLASTIC ANTIMETABOLITE in the treatment of COLON CANCER; BREAST CANCER and GASTRIC CANCER.

More From BioPortfolio on "Safety Study in Subjects With Metastatic Breast Cancer Who Progressed After Taxanes Treatment."

Quick Search


Relevant Topics

Breast Cancer
Track and monitor developments in breast cancer research and commercial development.  Follow the tabs above to read the latest global news, research, clinical trials on breast cancer and follow companies active in the development of breast cancer tr...

Surgical treatments
Surgery is a technology consisting of a physical intervention on tissues. All forms of surgery are considered invasive procedures; so-called "noninvasive surgery" usually refers to an excision that does not penetrate the structure being exci...

Biological Therapy
Biological therapy involves the use of living organisms, substances derived from living organisms, or laboratory-produced versions of such substances to treat disease. Some biological therapies for cancer use vaccines or bacteria to stimulate the body&rs...

Searches Linking to this Trial