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

The purpose of this study is to evaluate, in a first stage, the safety (incidence of cardiac toxicity) of Caelyx in combination with Trastuzumab and Docetaxel; and in a second stage, the tumor response rate of this regimen. This study will be conducted in approximately 30 centers. A total of approximately 70 to 95 subjects will be enrolled.


Eligibility Criteria:
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.