Cohort Study of Prospective Validation of Predictive Factors and Biological Imaging of Response to Bevacizumab and Paclitaxel in Patients With Metastatic Breast Cancer

Study Overview
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Brief Summary
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Bevacizumab plus chemotherapy improves response rates and prolongs PFS when used as first- and second-line therapy for advanced breast cancer. However, bevacizumab has not improved OS in the individual studies currently reported. In Europe, EMA has maintained its indication associated with weekly paclitaxel in first line metastatic breast cancer and more recently with capecitabine based on RIBBON 1 trial's results. The identification of patient subsets that receive the most clinical benefit would enable more specific treatment administration of bevacizumab and allow patients unlikely to benefit the opportunity to seek other treatment modalities. Unfortunately, despite efforts to identify patient subsets with a differential benefit from bevacizumab, no validated biomarkers have been defined. The Avastin cohort is a unique opportunity to investigate various biological and imaging parameters which could be related to clinical benefit of the combination of bevacizumab and weekly paclitaxel in first line metastatic breast cancer in a homogeneously treated population in French cancer centers. This trial will gather the expertise of several translational research platforms of different cancer centers from the UNICANCER consortium.

Official Title
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Cohort Study of Prospective Validation of Predictive Factors and Biological Imaging of Response to Bevacizumab (AVASTIN ®) in Combination With Weekly Paclitaxel Chemotherapy in First Line Treatment Patients With Metastatic Breast Cancer

Conditions
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Metastatic, 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: Male or female ≥18 years old. Histologically confirmed breast adenocarcinoma, metastatic (measurable or unmeasurable lesion), HER2 negative (on the last tumor tissue analyzed), Patient to receive first-line chemotherapy paclitaxel and bevacizumab in a weekly manner as recommended by the EMEA. Hormone receptor status known Eastern Cooperative Oncology Group (ECOG) performance status ≤2. Life expectancy ≥12 weeks. Women of childbearing age (except amenorrhea of at least 24 months) must have a negative pregnancy test serum within 28 days before starting treatment. In the absence of serum test, a urine pregnancy test (within 7 days before the first dose of bevacizumab) is required. Informed consent form duly signed and dated by patient Exclusion Criteria: Prior chemotherapy for metastatic disease ; Concomitant hormone therapy The patient must not have undergone radiation therapy for the treatment of metastatic disease (except cases of analgesic radiotherapy for bone pain due to metastases). Pregnant or nursing woman or woman of childbearing age (except amenorrhea for at least 24 months) who does not use an effective nonhormonal contraceptive method (intrauterine device, barrier method associated with the use of a spermicidal gel or surgical castration) for the duration of the study and 6 months after paclitaxel administration and / or bevacizumab. Man who does not accept to use effective contraception during the study period and 6 months after paclitaxel administration and / or bevacizumab. Known hypersensitivity to paclitaxel and / or to bevacizumab or to any excipients. Patient unable to undergo medical test for geographical, social or psychological reasons. Patient deprived of liberty or placed under the authority of a tutor

Ages Eligible for Study
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Minimum Age: 18 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cohort<br>first line treatment for metastatic breast cancer | Drug: Bevacizumab<br>* Treatments received by patients in this study are prescribed in the context of standard care<br>Drug: paclitaxel<br>* Treatments received by patients in this study are prescribed in the context of standard care<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measure of the initial rates and changes in CEC / CLC (Biological study) and measure of the visceral fat (imaging study) as predictors of progression-free survival (PFS) and response to bevacizumab and paclitaxel |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identification of new biomarkers as predictive factors of progression free survival (PFS), overall survival (OS) and of response to bevacizumab and paclitaxel. | These biomarkers will be selected from biological studies, proteomics and pharmacogenetics. | 2 years | 
| Quality of Life assessment |  | 2 years | 
| The Biomarkers selected from our biological, proteomic and pharmacogenetic studies will be correlated to the safety. |  | 2 years |