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Efficacy and Tolerance Study of Bevacizumab in Her2- Inflammatory Breast Cancer Patients

Phase 2
Completed
Conditions
Breast Cancer
Interventions
Registration Number
NCT00820547
Lead Sponsor
UNICANCER
Brief Summary

RATIONALE: Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving bevacizumab and combination chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving bevacizumab and radiation therapy after surgery may kill any tumor cells that remain after surgery.

PURPOSE: This phase II trial is studying giving bevacizumab together with chemotherapy before surgery and bevacizumab and radiation therapy after surgery to see how well it works in treating patients with inflammatory breast cancer.

Detailed Description

OBJECTIVES:

Primary

* Evaluate the complete histological response rate in patients with inflammatory HER2-negative breast cancer treated with bevacizumab and concurrent chemotherapy followed by bevacizumab and concurrent hormonal therapy after surgery and radiotherapy.

Secondary

* Evaluate the progression-fee and overall survival of these patients at 3 and 5 years.

* Evaluate the tolerance of bevacizumab in these patients.

* Assess circulating metastatic disease before, during, and after treatment.

* Assess circulating endothelial cells before, during, and after treatment.

* Assess predictive factors of response by genomic and proteomic studies on frozen tumor samples and fluid samples (i.e., serum and plasma).

OUTLINE: This is a multicenter study.

* Neoadjuvant induction therapy:

* Courses 1-4: Patients receive bevacizumab IV over 30-90 minutes, fluorouracil IV, epirubicin hydrochloride IV over 10 minutes, and cyclophosphamide IV over 5 minutes on day 1.

* Courses 5-8: Patients receive bevacizumab IV over 30-90 minutes and docetaxel IV over 1 hour on day 1.

Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity.

* Surgery: Patients undergo surgery 4-6 weeks after completion of bevacizumab.

* Adjuvant therapy: Beginning 2-4 weeks after surgery, patients undergo radiotherapy for 6 weeks. Patients also receive bevacizumab IV over 30-90 minutes beginning 2-4 weeks after surgery, during the radiotherapy period. Treatment with bevacizumab repeats every 3 weeks for 30 weeks in the absence of disease progression or unacceptable toxicity. Patients who are estrogen receptor- or progesterone receptor-positive (≥ 10% by IHC) receive the following concurrent hormonal therapy beginning in week 7:

* Premenopausal patients: Patients receive tamoxifen citrate for 5 years.

* Postmenopausal patients: Patients receive aromatase-inhibitor therapy (or tamoxifen citrate if unable to tolerate anti-aromatase therapy) for 5 years.

* Perimenopausal patients: Patients receive tamoxifen citrate for 2-3 years and aromatase-inhibitor therapy for 2-3 years OR tamoxifen citrate for 5 years followed by aromatase-inhibitor therapy for 2-3 years (if follicle-stimulating hormone \> 30 IU/L and/or estradiol \< 30 ng/L).

After completion of study treatment, patients are followed for at least 3 years.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
100
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
(FEC / Docetaxel) + Bevacizumabepirubicin hydrochlorideNeoadjuvant treatment: 4 cycles FEC + Bevacizumab followed by 4 cycles Docetaxel + Bevacizumab Adjuvant: Bevacizumab for 1 year
(FEC / Docetaxel) + BevacizumabbevacizumabNeoadjuvant treatment: 4 cycles FEC + Bevacizumab followed by 4 cycles Docetaxel + Bevacizumab Adjuvant: Bevacizumab for 1 year
(FEC / Docetaxel) + BevacizumabfluorouracilNeoadjuvant treatment: 4 cycles FEC + Bevacizumab followed by 4 cycles Docetaxel + Bevacizumab Adjuvant: Bevacizumab for 1 year
(FEC / Docetaxel) + BevacizumabcyclophosphamideNeoadjuvant treatment: 4 cycles FEC + Bevacizumab followed by 4 cycles Docetaxel + Bevacizumab Adjuvant: Bevacizumab for 1 year
(FEC / Docetaxel) + BevacizumabdocetaxelNeoadjuvant treatment: 4 cycles FEC + Bevacizumab followed by 4 cycles Docetaxel + Bevacizumab Adjuvant: Bevacizumab for 1 year
Primary Outcome Measures
NameTimeMethod
Complete histologic response ratePost surgery
Secondary Outcome Measures
NameTimeMethod
Genomic and proteomic analyses and correlation with histologic responsePost surgery
Progression-free survival3 and 5 years
Overall survival3 and 5 years
Predictive factors of response to bevacizumab3 and 5 years
Circulating peripheral cells (circulating endothelial and tumor cells): correlation of initial rate and association with histological response after surgeryPost-surgery
Toxicity as assessed by CTCAE v3.03 and 5 years

Trial Locations

Locations (28)

Centre Paul Papin

🇫🇷

Angers, France

Centre Hospitalier Regional de Besancon - Hopital Jean Minjoz

🇫🇷

Besancon, France

Institut Sainte Catherine

🇫🇷

Avignon, France

Institut Bergonie

🇫🇷

Bordeaux, France

Polyclinique Bordeaux Nord Aquitaine

🇫🇷

Bordeaux, France

Centre Regional Francois Baclesse

🇫🇷

Caen, France

Centre Jean Perrin

🇫🇷

Clermont-Ferrand, France

Centre de Lutte Contre le Cancer Georges-Francois Leclerc

🇫🇷

Dijon, France

CMC Les Ormeaux

🇫🇷

Le Havre, France

Centre Oscar Lambret

🇫🇷

Lille, France

Marseille Institute of Cancer - Institut J. Paoli and I. Calmettes

🇫🇷

Marseille, France

Centre Hospitalier General Andre Boulloche

🇫🇷

Montbeliard, France

Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle

🇫🇷

Montpellier, France

Centre Catherine de Sienne

🇫🇷

Nantes, France

Centre Antoine Lacassagne

🇫🇷

Nice, France

Institut Curie Hopital

🇫🇷

Paris, France

Clinique Armoricaine De Radiologie

🇫🇷

Saint Brieuc, France

Centre Alexis Vautrin

🇫🇷

Vandoeuvre-les-Nancy, France

Centre Leon Berard

🇫🇷

Lyon, France

Institut Jean Godinot

🇫🇷

Reims, France

Centre Eugene Marquis

🇫🇷

Rennes, France

Centre Rene Huguenin

🇫🇷

Saint Cloud, France

Hopitaux Universitaire de Strasbourg

🇫🇷

Strasbourg, France

Institut Gustave Roussy

🇫🇷

Villejuif, France

Centre Henri Becquerel

🇫🇷

Rouen, France

CRLCC Nantes - Atlantique

🇫🇷

Saint-Herblain, France

Centre Paul Strauss

🇫🇷

Strasbourg, France

Institut Claudius Regaud

🇫🇷

Toulouse, France

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