Docetaxel/Epirubicin/Bevacizumab as First Line Therapy for Metastatic HER2 Negative Breast Cancer

Study Overview
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Brief Summary
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This study will evaluate the efficacy and toxicity of docetaxel-epirubicin combination plus bevacizumab as first line treatment in patients with metastatic and HER2 negative breast cancer.

Detailed Description
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A phase II trial with 142 patients demonstrated that therapy with docetaxel plus epirubicin is highly active first-line therapy for metastatic breast cancer, with acceptable toxicity profile. Recently initial therapy of metastatic breast cancer with paclitaxel plus bevacizumab demonstrated prolonged progression-free survival, as compared with paclitaxel alone. This study will evaluate the efficacy and toxicity of docetaxel-epirubicin combination plus bevacizumab as first line treatment in patients with metastatic and HER2 negative breast cancer. Furthermore, the efficacy of the combination therapy will be correlated with the presence of circulating tumor cells (CTCs) in this population.

Official Title
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Docetaxel-epirubicin Plus Bevacizumab as First Line Therapy for Patients With Metastatic and HER2 Negative Breast Cancer. A Multicenter Phase I-II Study

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Docetaxel
* Drug: Epirubicin
* Drug: Bevacizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically- or cytologically- confirmed metastatic breast adenocarcinoma No HER2 overexpression or gene amplification No previous therapy for metastatic breast cancer is allowed Age 18-75 years At least 12 months interval since prior adjuvant therapy with taxanes and/or anthracyclines Measurable disease as defined by the presence of at least one measurable lesion (except bone metastases, ascites or pleural effusions) Performance status (WHO) 0-2 Adequate liver (serum bilirubin <1.5 times the upper normal limit, AST and ALT <2.5 times the upper normal limit in the absence of demonstrable liver metastases, or <5 times the UNL in the presence of liver metastases) Adequate renal function (serum creatinine <1.5 times the upper normal limit Adequate bone marrow function (neutrophils ≥ 1.5x 109 /L, and platelets ≥ 100x 109 /L) Written informed consent Exclusion Criteria: Active infection Brain metastases History of significant cardiac disease (unstable angina, congestive heart failure, myocardial infarction within the previous 6 months, ventricular arrhythmias) History of stroke Anticoagulation therapy (except of low dose aspirin <325mg) Other invasive malignancy except nonmelanoma skin cancer Psychiatric illness or social situation that would preclude study compliance Pregnant or lactating women

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Bevacizumab->Epirubicin->Docetaxel | Drug: Docetaxel<br>* Docetaxel as an IV infusion over 1h at the dose of 75mg/m2 every 3 weeks for 6 cycles<br>* Other names: Taxotere;Drug: Epirubicin<br>* Epirubicin as an IV infusion over 10 min at the dose of 75mg/m2 every 3 weeks for 6 cycles<br>* Other names: Farmorubicine;Drug: Bevacizumab<br>* Bevacizumab as an IV infusion over 1h at the dose of 15 mg/kg every 3 weeks for 6 cycles<br>* Other names: Avastin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate |  | Objective responses confirmed by CT or MRI (on 3rd and 6th cycle) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity assessment |  | Toxicity assessment on each cycle | 
| Time to Tumor Progression |  | 1 year | 
| Overall Survival |  | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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breast cancer, chemotherapy, biological therapy