A Study to Determine the Activity of Caelyx With Trastuzumab and Docetaxel in the Treatment of Metastatic Breast Cancer (Study P03679)
Condition: Breast Neoplasm
MeSH terms: Breast Neoplasms
Intervention: Pegylated Liposomal Doxorubicin; Docetaxel; Trastuzumab
Intervention description: Stage 1: 25 subjects will be treated with Caelyx IV 30 mg/m^2 on day 1, every 3 weeks
Stage 2: 45 new patients will be treated at the recommended dose level (defined in the first step) on day 1, every 3 weeks.; Stage 1 and Stage 2: Docetaxel 60 mg/m2 IV as 1-hour infusion, on day 1, every 3 weeks.; Stage 1 and Stage 2: 4 mg/kg IV 90-minute infusion loading dose. Then 2 mg/kg IV weekly during 6 cycles (18 weeks).
Intervention MeSH terms: Docetaxel; Doxorubicin; Liposomal doxorubicin; Trastuzumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 27.0
Sex: Female
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No

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.