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

Conditions

• BRMS1
• Patient With Progression After Taxanes
• Patient With a Maximum of One Chemotherapy
• Performance Status Zero to Two for Beginning the Study

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Lapatinib Vinorelbine — DRUG
  The starting dose of vinorelbine is 25 mg/m2/ IV days 1 and 8, every 21 days. A daily dose of Lapatinib is 5 tablets (1250 mg of Lapatinib) taken approximately at the same time each day.
• Lapatinib Capecitabine — DRUG
  The starting dose of capecitabine is 2000 mg/m2/day, to be divided and given twice daily orally, 12 hours apart, for 14 days, every 21 days. A daily dose of Lapatinib is 5 tablets (1250 mg of Lapatinib) taken approximately at the same time each day.
• Gemcitabine Lapatinib — DRUG
  The starting dose of gemcitabine is 1000mg/m2/ IV days 1 and 8, every 21 days. A daily dose of Lapatinib is 5 tablets (1250 mg of Lapatinib) taken approximately at the same time each day.

Study Details

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.

Key Dates

Start date

Nov 30, 2009

Status verified

Nov 2010

Primary completion

Dec 31, 2010

Completion

Sep 30, 2011

Study Design

Enrollment

142 participants (actual)

Allocation

RANDOMIZED

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Arms

• Active Comparator: Capecitabine Lapatinib
  The starting dose of capecitabine is 2000 mg/m2/day, to be divided and given twice daily orally, 12 hours apart, for 14 days, every 21 days. A daily dose of Lapatinib is 5 tablets (1250 mg of Lapatinib) taken approximately at the same time each day.
• Experimental: Vinorelbine Lapatinib
  The starting dose of vinorelbine is 25 mg/m2/ IV days 1 and 8, every 21 days. A daily dose of Lapatinib is 5 tablets (1250 mg of Lapatinib) taken approximately at the same time each day.
• Experimental: Gemcitabine Lapatinib
  The starting dose of gemcitabine is 1000mg/m2/ IV days 1 and 8, every 21 days. A daily dose of Lapatinib is 5 tablets (1250 mg of Lapatinib) taken approximately at the same time each day.

Primary Outcome Measure

Clinical benefit rate [ Time Frame: 6 months ]