Dose Finding Study for Combination of Capecitabine, Lapatinib and Vinorelbine in Metastatic Breast Cancer

Combinational Therapy of Capecitabine, Lapatinib and Vinorelbine for the Treatment of Patients With her2/Neu Positive, Relapsed or Metastatic Breast Carcinoma Following Treatment Failure With Trastuzumab

The purpose of the study is to investigate safety and efficiency of the triple combination of capecitabine, lapatinib and vinorelbine in patients with metastatic breast cancer.

The combination of lapatinib with capecitabine ist a standard therapy für Her2 positive metastatic breast cancer. This study combines this therapy with the additional antimitotic mode of function by vinorelbine.

Key Inclusion Criteria:

• Written informed consent
• Able to comply with the protocol
• ECOG performance status 0-1
• Adequate contraception
• Confirmed Her2/neu-positive, adenocarcinoma of the breast
• At least one measurable lesion according to RECIST 1.1 criteria
• First or second chemotherapy after diagnosis of metastasis
• Lapatinib treatment indicated (adjuvant trastuzumab treatment <12 months ago or progressive disease with trastuzumab treatment)
• No signs and symptoms of CHF (chronic heart failure), LVEF (left ventricular ejection fraction) at study start at least 55%
• Adequate hepatic and renal function value
• Adequate hematologic function values

Exclusion Criteria:

• Pregnant or lactating women
• Concurrent participation in another clinical trial. Prior participation is allowed if the last study medication was administered more than 4 weeks prior to randomization
• Asymptomatic with regards to tumor illness
• Previous treatment with lapatinib, capecitabine or vinorelbine
• Necessity of planned treatment with other chemotherapeutics oder anti-hormone therapy
• Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to randomization, or anticipation of the need for major surgery during the course of the study
• Evidence of cardiovascular disease, e.g. myocardial infection, unstable angina pectoris or arrhythmia
• History of vascular or cardiovascular disease within the past 6 months
• All illnesses that result in malabsorption of oral medication or inability to take oral medication
• Concurrent treatment with anti-viral drugs based on sorivudine or with aminoglycosides
• Concurrent treatment with any drug interfering with study medication, especially, those that induce CYP3A
• Concurrent treatment with allopurinol
• Other malignancies (except for basal cell carcinoma of the skin and cervical carcinoma in situ); patient can be included in the study if no recurrent disease has been observed for at least 5 years
• Concurrent illnesses or other circumstances that could interfere with trial participation, efficacy or safety of the patient