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

Study Overview
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Brief Summary
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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.

Official Title
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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.

Conditions
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Breast Neoplasm

Intervention / Treatment
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* Drug: Pegylated Liposomal Doxorubicin
* Drug: Docetaxel
* Drug: Trastuzumab


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Caelyx, Docetaxel, Trastuzumab<br>Stage 1: subjects will receive Caelyx one day every 3 weeks in combination with docetaxel one day every 3 weeks and trastuzumab once weekly during 6 cycles. At the end of this stage, based on the number of cardiac events, subjects will proceed to a second stage or restart with a lower dose of Caelyx. Stage 2: subjects will be treated with the recommended dose of Caelyx (defined in the first stage) in combination with docetaxel and trastuzumab. | Drug: Pegylated Liposomal Doxorubicin<br>* 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.<br>* Other names: Caelyx;Drug: Docetaxel<br>* Stage 1 and Stage 2: Docetaxel 60 mg/m2 IV as 1-hour infusion, on day 1, every 3 weeks.<br>* Other names: Taxotere;Drug: Trastuzumab<br>* 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).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Had a Tumor Response, According to Standard RECIST (Response Evaluation Criteria in Solid Tumors) Criteria | Those who achieved either complete (disappearance of all target lesions) or partial (at least 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD) response. | Week 09, Week 18, at the end of each patient's treatment, and at 3, 6, 9, and 12 months after end of treatment. |