Weekly Paclitaxel/Carboplatin/Bevacizumab as First Line Therapy for Triple Negative Breast Cancer

Study Overview
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Brief Summary
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This study will evaluate the efficacy of weekly paclitaxel-carboplatin combination plus bevacizumab as first line treatment in patients with metastatic triple negative breast cancer. Furthermore, the efficacy of the combination therapy will be correlated with the presence of circulating tumor cells (CTCs) in this population

Detailed Description
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Breast cancer with absent or low expression of hormone receptors and HER2 (triple negative) does not respond to hormonal or biological therapy with trastuzumab. However, triple negative breast cancers are highly sensitive to chemotherapy. The combination of paclitaxel and carboplatin administered on a weekly basis is active and well tolerated. Recently, initial therapy of metastatic breast cancer with paclitaxel plus bevacizumab demonstrated prolonged progression-free survival, as compared with paclitaxel alone

Official Title
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Weekly Paclitaxel-carboplatin Plus Bevacizumab as First Line Therapy for Patients With Triple Negative (ER-,PR-,HER2-) Metastatic Breast Cancer. A Multicenter Phase I-II Study

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Carboplatin
* Drug: Bevacizumab
* Drug: Paclitaxel


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 Absent or low ER or PR expression No previous therapy for metastatic breast cancer is allowed Age 18-75 years 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 upper normal limit in the presence of liver metastases) adequate renal function (serum creatinine <1.5 times the upper normal limit) bone marrow (neutrophils ≥ 1.5x 109 /L, and platelets ≥ 100x 109 /L) No radiation of measurable disease (except brain metastases) No progressive brain metastases according to clinical or radiological criteria No brain metastases without prior radiation therapy Written informed consent Exclusion Criteria: Active infection 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Paclitaxel/Carboplatin/Bevacizumab | Drug: Carboplatin<br>* Carboplatin (IV) 2 AUC on day 1,8,15. Treatment repeats every 4 weeks until progression<br>Drug: Bevacizumab<br>* Bevacizumab (IV) 10 mg/kg on day 1,15. Treatment repeats every 4 weeks until progression<br>* Other names: Avastin;Drug: Paclitaxel<br>* Paclitaxel (IV) 90 mg/m2,on day 1,8,15. Treatment repeats every 4 weeks until progression<br>* Other names: Taxol;|

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 profile |  | Toxicity assessment of each chemotherapy 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, Triple negative, Chemotherapy, Anti-angiogenesis therapy