Pegylated Liposomal Doxorubicin (Caelyx) in Combination With Herceptin and Taxotere as First-line Chemotherapy in Metastatic Breast Cancer Patients: A 2 Stage Phase II, Open Label, Multicenter Study.
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
- 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.
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
- 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.