Breast Cancer
Conditions
Keywords
breast cancer
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.
Interventions
DRUGno bevacizumab
no bevacizumab
DRUGbevacizumab
Patients receive on day 1 of each cycle : bevacizumab 15 mg/kg (8 injections in total).
Sponsors
Institut Paoli-Calmettes
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 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 pathological complete response rate | 8 months | Evaluation of the pathological complete response rate according to the classification of Sataloff |
Countries
France
Outcome results
None listed