Docetaxel, Gemcitabine and Bevacizumab for Metastatic Breast Cancer

Study Overview
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Brief Summary
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This study will evaluate the efficacy and toxicity of docetaxel, gemcitabine and bevacizumab combination, administered biweekly, as salvage treatment in patients with metastatic and HER2 negative breast cancer.

Detailed Description
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Docetaxel plus gemcitabine is an active combination in the salvage treatment for metastatic breast cancer. Administered every two weeks, this combination has a favorable toxicity profile, and promising activity in > 1st line treatment for metastatic breast cancer. 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 addition of bevacizumab to a biweekly regimen of docetaxel and gemcitabine in the salvage therapy for metastatic breast cancer.

Official Title
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Docetaxel, Gemcitabine and Bevacizumab as Salvage Therapy for Metastatic Breast Cancer

Conditions
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Breast Cancer

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


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 At least one previous chemotherapy regimen for metastatic breast cancer Age ≥18 years Performance status (WHO) 0-2 Life expectancy of at least 12 weeks Measurable disease as defined by at least 1 bidimensionally measurable lesion ≥ 20 X 10 mm Performance status (WHO) 0-2 Adequate liver function (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 upper normal limit in the presence of liver metastases), adequate renal function (serum creatinine <1.5 times the upper normal limit) and bone marrow ≥ 1,500/mm3, PLT ≥ 100,000/mm3, Hgb ≥ 9 g/dL) function Written informed consent Exclusion Criteria: Pregnant or lactating women Progressive brain metastases according to clinical or radiological criteria Brain metastases without prior radiation therapy Radiation therapy within the previous 4 weeks Previous radiation therapy to the only measurable lesion Proteinuria ≥ 500 mgr of protein daily Uncontrolled hypertension Documented hemorrhagic diathesis or coagulation disorder Cardiovascular disease (class II-IV NYHA congestive heart failure, myocardial infarction within the previous 4 months, unstable angina, LVEF < normal, ventricular arrhythmia, uncontrolled hypertension) Thrombotic event within the previous 6 months Concurrent use of aspirin > 325 mgr daily, low molecular weight heparin in therapeutic dose, warfarin or acenocoumarol, non-steroid anti-inflammatory agents Major surgical procedure within the previous 4 weeks Presence of nonhealing wound or fracture Peripheral neuropathy > grade 2 according to the NCI CTCAE (version 3.0) Any sustained chronic toxicity > grade 2 according to the NCI CTCAE (version 3.0) Uncontrolled infection Any serious, uncontrolled comorbidity on the investigator's judgment Other cancer within the previous 5 years, except non-melanoma skin cancer and in situ cervical cancer Serious psychiatric illness

Ages Eligible for Study
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Minimum Age: 18 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: 1<br>Bevacizumab->Docetaxel->Gemcitabine | Drug: Bevacizumab<br>* Bevacizumab (IV) 10 mgr/Kgr on days 1 and 15 every 4 weeks for 6 cycles followed by Bevacizumab (IV) 15 mgr/Kgr on day 1 every 3 weeks until disease progression<br>* Other names: Avastin;Drug: Docetaxel<br>* Docetaxel (IV) 65 mg/m2 on days 1 and 15 every 4 weeks for 6 cycles<br>* Other names: Taxotere;Drug: Gemcitabine<br>* Gemcitabine (IV) 1500 mg/m2 on days 1 and 15 every 4 weeks for 6 cycles<br>* Other names: Gemzar;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate |  | up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival |  | 1 year | 
| Toxicity profile |  | 21 days | 
| Overall Survival |  | 1 year | 
| Quality of life assessment |  | Assessment every two cycles | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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docetaxel, gemcitabine, bevacizumab, chemotherapy