Anti Cancer Stem Cell Activity of Pre-operative Bevacizumab and Chemotherapy in Breast Cancer

Phase 2

Completed

Brief Summary: The purpose of this study is to evaluate anti-cancer stem cell (CSC) activity (measured by the amount of Aldehyde dehydrogenase 1/ALDH1+ cells before and after treatment) of pre-operative bevacizumab in combination with conventional chemotherapy in breast cancer receiving neo-adjuvant treatment, compared to a control arm receiving chemotherapy alone.

Recruitment & Eligibility

Inclusion Criteria

Women older than 18 ys
Primary breast cancer treated in the neoadjuvant setting (synchronous metastatic disease are eligible)
Primary breast tumor accessible to initial biopsy
White Blood Count > 3.000/µl and Absolute neutrophil count ≥ 1.500/µl AND platelets ≥ 100 x 109/L AND Hemoglobin ≥ 9 g/dL, Serum creatinine ≤ 150µm/l• Urine dipstick for proteinuria < 2+. Patients discovered to have ≥ 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate ≤ 1 g of protein in 24 hours, Total bilirubin ≤ 1.5 ULN and ASAT < 2.5 ULN AND ALAT < 1.5 ULN (2.5 if liver metastasis), Adequate coagulation function: International normalized ratio (INR) ≤ 1.5 and TCA ≤ 1.5 x ULN
Left ventricular ejection fraction (LVEF) ≥ 55% (isotopic or
ultrasound methods)
Karnofsky Index > 1 ; Performance status 0 to 1
Patients must have signed a written informed consent form prior to any study specific screening procedures
Patient affiliated to the national "Social Security" regimen or beneficiary of this regimen.

Exclusion Criteria

Previous history of cancer (other than curatively treated basal and squamous cell carcinoma of the skin and/or in-situ carcinoma of the cervix) relapsing within the 5 years before study entry
Known contra-indication to anticancer compounds used
Uncontrolled hypertension (systolic >150 mmHg and/or diastolic >100 mmHg) or history of hypertensive encephalopathy
History of inherited diathesis or recent thrombotic events
Non-healing wound, active peptic ulcer or bone fracture.
Major surgery or significant traumatic injury within 28 days prior to study treatment start
History of abdominal fistula, trachea-oesophageal fistula or urinary fistula
Use of Non Steroid Anti Inflammatory or full dose anticoagulants or antiaggregation treatments within 10 days
Pregnancy and breast feeding, premenopausal patient and no effective contraception
Brain metastasis.
Any unstable severe disease such as : uncontrolled cardiac or vascular disease, uncontrolled hemorrhagy, uncontrolled neuropsychiatric disorders, including dementia, uncontrolled infection or any severe disorders that may preclude study participation
Patient considered geographically, socially or psychologically unable to comply with the treatment and the required medical follow-up.

Arm && Interventions

Group	Intervention	Description
without bevacizumab	no bevacizumab	4 cycles 5-fluorouracil 500 mg/m² IV + epirubicin 100 mg/m² IV + cyclophosphamide 500 mg/m² IV of (FEC100) every 21 days and 4 cycles of docetaxel 100 mg/m² IV every 21 days. Patients with HER2+ disease will receive trastuzumab (8 mg/kg (IV then 6 mg/kg, every 21 days), which will be started with docetaxel and administered for a total duration of 54 weeks, 18 injections.
WITH bevacizumab	bevacizumab	bevacizumab 15 mg/kg on day 1 of each cycle : 4 cycles of 5-fluorouracil 500 mg/m² IV + epirubicin 100 mg/m² IV + cyclophosphamide 500 mg/m² IV (FEC100) every 21 days and 4 cycles of docetaxel 100 mg/m² IV every 21 days. Patients with HER2+ disease will receive trastuzumab (8 mg/kg (IV then 6 mg/kg, every 21 days), which will be started with docetaxel and administered for a total duration of 54 weeks, 18 injections.

Primary Outcome Measures

Name	Time	Method
Measure of the anti-cancer stem cell activity	4 months	The anti-cancer stem cell (CSC) activity is measured by the amount of Aldehyde dehydrogenase 1/ALDH1+ cells after 4 cycles of treatment compared to the amount before treatment

Secondary Outcome Measures

Name	Time	Method
Evaluation of the disease-free survival, recurrence-free survival and overall survival	5 years	The disease-free survival, recurrence-free survival and overall survival are calculated from the inclusion to the time of the event
Evaluation of the safety of the treatment	8 months	Evaluation of the safety of the treatment at each cycle, estimated by the number of patients with clinical and biological adverse events coded according to the CTCAE
Evaluation of the pathological complete response rate	8 months	Evaluation of the pathological complete response rate according to the classification of Sataloff

Locations (3): Jean-Marc EXTRA, MD
🇫🇷
Marseille, France
Jean-Yves PIERGA
🇫🇷
Paris, France
Hervé CURE
🇫🇷
Reims, France