Study to Compare Vinorelbine In Combination With the mTOR Inhibitor Everolimus vs. Vinorelbin Monotherapy for Second-line Treatment in Advanced Breast Cancer

Inclusion criteria

1 .Dated and signed patient informed consent before start of any in the protocol specified procedures 2. Histologically or cytologically confirmed Her2/neu negative, metastatic or locally advanced breast cancer, including inoperable local relapse, with measurable or non-measurable lesions for which

• a palliative second line chemotherapy is indicated. Antihormone palliative pretreatments do not count as separate treatment lines
• treatment with anthracycline and/or taxanes has failed or is not suitable
• which cannot be adequately treated by operation or radiotherapy on its own 3. An exclusive anti-hormone therapy is not indicated for the patient 4. ECOG Performance Status of 0-2 5. Women >= 18 years of age 6. Life expectancy of at least 12 weeks 7. Adequate bone marrow, liver and renal function (according to SmPC of Vinorelbine, Afinitor®) based on laboratory assessments raised within 7 days prior to start of study treatment:
• Haemoglobin >= 9.0 g/dl
• Absolute neutrophil count (ANC) >= 2/mm³
• Thrombocytes >= 100/µl
• INR >= 2
• Serum bilirubin =< 1.5x upper limit of normal ( in patients with known Gilbert syndrome, total bilirubin =< 3x upper limit of normal, with direct bilirubin =< 1.5x upper limit of normal
• ALT and AST =< 2.5x upper limit of normal (=< 5x upper limit of normal in subjects with liver metastases)
• Serum cholesterol =< 300 mg/dl or 7.75 mmol/l and triglycerides =< 2.5x upper limit of normal (with lipid lowering drugs permitted)
• Serum creatinin =< 2x upper limit of normal 8. Documentation of a negative pregnancy test in women of childbearing potential within 7 days prior to start of study. Sexual active pre-menopausal women are required to use adequate contraception throughout the duration of the study, except for oestrogen containing contraceptives

Exclusion criteria

• Previous treatment with Vinorelbine or an inhibitor of mTOR
• Treatment with other study medication within 28 days before start of treatment
• Patients who have received prior radiotherapy to ≥ 25% of the bone marrow
• Other tumours in the previous 5 years with exception of an adequately treated basal cell carcinoma of the skin or a preinvasive cervix carcinoma
• Simultaneous use of known CYP3A4 inducers (e.g. Phenytoin, Rifampicin) or inhibitors of this enzyme (e.g. Itraconazole, Ketoconazole), therefore also use of mistletoe, St John's wort or grapefruit juice
• Patients to whom at least one of the conditions applies:

• Substance abuse
• medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results as judged by the investigator
• Legal incapacity or limited legal capacity
• Subjects who are unable to take oral medication
• Any condition that could jeopardise the safety of the patient and their compliance in the study as judged by the investigator
• History of cardiac dysfunction including one of the following:

• Myocardial infarction by elevated cardiac enzymes or persistent regional wall abnormalities on assessment of LV function
• History of documented congestive heart failure (NYHA ≥ 3)
• Documented cardiomyopathy
• Known HIV infection or chronic hepatitis B or C or history of hepatitis B / C
• Active clinically relevant infection (> grade 2 NCI-CTC Version 4.03)
• Clinical or radiological detection of CNS metastases
• Patients receiving concomitant immunosuppressive agents or chronic use of corticosteroids at the time of study entry except in cases outlined below:

• topical applications (e.g. rash,) inhaled sprays, (e.g. obstructive airway diseases) eye drops or local injections (e.g. intraarticular) are allowed
• Active bleeding diathesis or an oral anti-vitamin K medication (except low-dose warfarin and aspirin or equivalent, as long as the INR ≤ 2)
• Kidney function disorder requiring dialysis
• Seriously impaired liver function (Child-Pugh, class C)
• Known hypersensitivity reaction to Vinorelbine or Everolimus
• Pregnant or breast-feeding subjects