A Phase IB/II Trial of Combination of Vinorelbine With Sorafenib (BAY 43-9006) as First-Line Treatment in Patients With Metastatic Breast Cancer
- Women affected by histologically proven metastatic breast cancer.
- Tumor not susceptible to therapy with trastuzumab, defined as FISH negative for HER-2
amplification or immunohistochemistry 0-1+ for HER-2 expression.
- Female, age ≥ 18.
- Documented measurable disease by appropriate radiologic imaging according to RECIST
criteria (see Appendix E). Lesions in previously irradiated areas are not considered
measurable disease, unless progression has been documented post-radiation.
- ECOG performance status 0-1 (see Appendix B)
- Life expectancy > 6 months.
- Adequate bone marrow function, as indicated by:
- Hemoglobin ≥ 90 g/L
- Neutrophils ≥ 1.5 x 109/L
- Platelets ≥ 100 x 109/L
- Adequate renal function, as indicated by serum creatinine ≤1.5 times the upper limit
of normal and/or Creatinine Clearance calculated as >50% lower normal limit, or
estimated as ≥ 50 ml/min (Appendix C).
- Adequate liver function, as indicated by:
- bilirubin ≤ 1.5 times upper normal limit;
- AST and ALT ≤ 2 times upper normal limit.
- Left ventricular ejection fraction (LVEF) ≥50% as measured by either multigated
acquisition (MUGA) scan or echocardiogram (ECHO).
- No therapy for breast cancer in the 4 weeks preceding the therapy start.
- Women of childbearing potential must be using adequate contraception and have a
negative pregnancy test at the time of enrollment.
- Patient able to understand and give written informed consent.
- Patients with locally advanced breast cancer or stage IIIb only.
- Presence of only non-measurable disease.
- Previous (neo)adjuvant chemotherapy with vinorelbine.
- Any previous anti-angiogenic therapy.
- Any previous chemotherapy for metastatic breast cancer. Previous hormonal treatments
or radiotherapy for metastatic disease are allowed.
- Radiotherapy, chemotherapy or hormonal therapy for breast cancer in the last 4 weeks
prior to starting the study treatment.
- Major surgery within 4 weeks of first study treatment, or minor surgery (including
placement of an access device) within 7 days of therapy start.
- Presence of life-threatening disease or central nervous system localizations.
- Evidence of HER-2 positive breast cancer, defined as FISH-positive for amplification
or score 3+ by immunohistochemistry.
- Any other possibly active primary tumor, except basal cell carcinoma of the skin, or
carcinoma in situ of the cervix.
- Clinically significant hepatic disease with respect to hepatitis B, hepatitis C,
cirrhosis or other liver diseases.
- Uncontrolled bacterial, viral or fungal infection.
- Previous history of ischemic disease.
- Patients with previous history of thrombo-embolic events, or with documented risk
factors for thrombotic disease other than cancer.
- History of gross hemorrhage within the past 6 months (e.g., hemoptysis or hematuria
requiring medical intervention).
- Uncontrolled hypertension.
- Other serious medical conditions, such as uncontrolled cardiac disease, severe
pulmonary disease, uncontrolled diabetes.
- Patient exhibiting confusion or disorientation.
- Any condition (medical, social, psychological, geographical) that would prevent
- Patient is pregnant, or is breast-feeding, or is unwilling to use adequate
- Failure to give informed consent.