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.

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.

http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final\_Updated%20July\_9\_2014.pdf

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