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

Institut Paoli-Calmettes

Status and phase: Completed; Phase 2

Conditions: Breast Cancer

Treatments: Drug: bevacizumab; Drug: no bevacizumab

Study type: Interventional

Funder types: Other

Identifiers

NCT01190345

AVASTEM/IPC 2009-001

Details and patient eligibility

About

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.

Enrollment: 75 estimated patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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75 participants in 2 patient groups

WITH bevacizumab

Experimental group

Description:

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.

Treatment:

Drug: bevacizumab

without bevacizumab

Active Comparator group

Description:

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.

Treatment:

Drug: no bevacizumab