A Biomarker Study in Patients With HER2-negative Metastatic Breast Cancer Treated With Bevacizumab and Paclitaxel

Study Overview
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Brief Summary
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To explore molecular biomarkers and/or gene expression signatures that predict response to bevacizumab given in combination with paclitaxel as first line therapy in HER2 negative metastatic breast cancer (MBC).

Detailed Description
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This is a prospective, randomized, 2-arm, open-label, single-center, phase II trial. A total of 30 patients will be included during a period of 2 years. The study will be initiated with a non-randomized, feasibility stage including ten patients who will be treated with bevacizumab and paclitaxel, in order to determine the safety of metastatic tumor biopsies during therapy with bevacizumab. In the second phase, patients will be randomized (1:1) between two treatment arms: A. Bevacizumab + paclitaxel and B. Paclitaxel

Official Title
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A Prospective Randomized Phase II Study to Identify Predictive Biomarkers and Mechanisms of Therapy Resistance in Patients With HER2-negative Metastatic Breast Cancer Treated With the Combination of Bevacizumab and Paclitaxel (BEVPAC).

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Bevacizumab
* Drug: Paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-70 years. Performance status ECOG 0-2. Clinically and / or radiologically proven stage IV or recurrent HER2 negative breast cancer. At least one tumor lesion accessible for biopsy. This lesion may not have been treated previously with irradiation. Clinically and/or radiographically documented measurable disease according to RECIST v1.1 criteria. At least one site of disease must be unidimensionally measurable as follows: CT-scan, physical exam ≥ 10 mm} Chest X-ray ≥ 20 mm }see Eisenhauer et al. for more details Lymph node short axis ≥ 15 mm } All radiology studies must be performed within 28 days prior to registration (35 days if negative). Adequate bone-marrow, hepatic and renal function defined as laboratory tests within 7 days prior to enrollment: Haematology: Absolute granulocytes > 1.5 x 109/L Platelets > 100 x 109/L Biochemistry:Bilirubin within normal limits Serum creatinine within normal limits APTT and INR within normal limits within 7 days prior to enrollment. Adequate cardiac function with Left Ventricular Ejection Fraction (LVEF) within normal limits determined by echocardiogram or MUGA within 28 days prior to inclusion. Written informed consent must be given. Exclusion Criteria: Previous systemic treatment for MBC. Major surgery less than 28 days prior to enrollment. Concurrent malignancy of any site, except adequately controlled limited basal cell carcinoma or squamous-cell carcinoma of the skin or carcinoma in situ of the cervix. Bleeding diathesis, history of thromboembolic disease, or ongoing treatment with warfarin, heparin analogs or antiplatelet drugs. Major cardiac comorbidity. Previous treatment with bevacizumab. Previous allergic reaction to taxane analogs. Ongoing pregnancy or lactation. Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.

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

Sexes Eligible for Study
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All

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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm A<br>Arm A and feasibility phase: Bevacizumab 15mg/kg administered iv every 3 weeks in combination with paclitaxel 80mg/m2 iv weekly. | Drug: Bevacizumab<br>* 15mg/kg administered iv every 3 weeks in combination with paclitaxel 80mg/m2 iv weekly<br>* Other names: Avastin;Drug: Paclitaxel<br>* 80mg/m2 iv weekly<br>* Other names: Taxol;|
| Active Comparator: Arm B<br>Arm B: Paclitaxel 80mg/m2 iv weekly. | Drug: Paclitaxel<br>* 80mg/m2 iv weekly<br>* Other names: Taxol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identification of molecular biomarkers | To explore molecular biomarkers and/or gene expression signatures that predict response to bevacizumab given in combination with paclitaxel as first line therapy in HER2 negative MBC. | After the study completion,After completion of the study, which will take up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of metastatic biopsies during bevacizumab therapy | The safety objective of the study is to assess whether carrying out metastatic tissue biopsies during treatment with bevacizumab is safe. For this reason, the study will be initiated with a feasibility phase of 10 patients and will be continued to the randomized phase only if the study specific procedures prove to be safe. | continuous assessment and after inclusion of 10 patients, After completion of the study which will take up to 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metastatic breast cancer