a study to determine the activity of caelyx with trastuzumab and docetaxel in the treatment of metastatic breast cancer (study p03679)

Conditions: Breast Neoplasm

Summary: 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.