A Study to Determine the Activity of Caelyx With Trastuzumab and Docetaxel in the Treatment of Metastatic Breast Cancer (Study P03679)

Inclusion criteria

Patients must fulfill all the following criteria:

• Females aged 18 to 70 years-old.
• Willingness to participate in the study and comply with its procedures.
• Documented diagnosis of metastatic breast carcinoma (stage IV) Human Epidermal Growth Factor Receptor 2 (HER2) overexpressing (Immunohistochemistry (IHC) 3+ or Fluorescence In Situ Hybridization(FISH) +).
• No prior chemotherapy for metastatic breast cancer.
• Adjuvant or neo-adjuvant chemotherapy is allowed according to the following rules:

• patients treated with anthracyclines if all the following conditions are met:

• Doxorubicin total dose <= 300 mg/m^2
• Epirubicin total dose <= 480 mg/m^2
• Chemotherapy-free interval of > 12 months
• no taxane-based adjuvant or neo-adjuvant chemotherapy is allowed;
• patients treated with non-anthracycline/taxane adjuvant or neo-adjuvant chemotherapy regimens are freely eligible (i.e. cyclophosphamide/methotrexate/fluorouracil (CMF) or similar regimens).
• At least one measurable lesion according to RECIST criteria.
• Complete hematologic and biologic baseline evaluation within 2 weeks prior to start of treatment.
• Complete Tumor baseline evaluation including a total body computed tomography (CT) scan within 4 weeks prior to start of treatment.
• Left ventricular ejection fraction (LVEF) >= 50% as determined by echocardiogram or Multi Gated Acquisition (MUGA) scan.
• World Health Organization (WHO) performance status 0,1.
• Life expectancy > 3 months.
• Laboratory requirements :

• Hematology :

• Neutrophils > 1.5 x 10^9/L
• Platelets > 100 x 10^9/L
• Hemoglobin > 10 g/dL
• Hepatic function:

• Total bilirubin <= 1.25 x the upper-normal limits (UNL);
• ASAT (Aspartate Aminotransferase or SGOT), ALAT (Alanine aminotransferase or SGPT) <= 2.5 x the upper-normal limits;
• For patients with liver metastases:

• Total bilirubin < 1.5 x the UNL (Upper limit of normal) ;
• ASAT and/or ALAT < 3 x the UNL;
• Renal function :

• Serum Creatinine < 1.5 x the UNL.
• Women of child bearing potential must have a negative serum pregnancy test and be using adequate contraception.
• Patients must be accessible for treatment and follow-up.

Exclusion criteria

Patients will not be enrolled if any of the following criteria apply:

• Prior chemotherapy for metastatic disease.
• History of prior malignancy in the last 10 years (other than non melanoma skin cancer or excised cervical carcinoma in situ).
• Radiation to disease areas within 3 weeks of study initiation.
• Symptomatic peripheral neuropathy > grade 2 according to the National Cancer Institute (NCI) Common Toxicity Criteria.
• Other serious illness or medical condition.
• LVEF < 50% as determined by echocardiogram or MUGA scan.
• Congestive hearth failure or angina pectoris even if it is medically controlled. Previous history of myocardial infarction within 1 year from study entry, uncontrolled high risk hypertension or arrhythmia.
• History of significant neurologic or psychiatric disorders including dementia or seizures.
• Active infection.
• Active peptic ulcer, unstable diabetes mellitus or other contraindications for the use of dexamethasone.
• Concurrent treatment with other experimental drugs. Participation in another clinical trial with any investigational drug within 30 days prior to study screening.
• Concurrent treatment with corticosteroids used for reasons other than for premedication. However patients receiving chronic treatment with corticosteroids (> 6 months) at low dose (< 20 mg of methylprednisolone or equivalent dose of other corticosteroids) for whichever reason are eligible.
• Taxane-based adjuvant or neo-adjuvant chemotherapy < 12 months.
• Other concurrent chemotherapy, immunotherapy, radiotherapy or any other investigational medication, for the treatment of the tumor.
• Pregnant or breast-feeding women.