Phase II" Proof of Concept " Trial Evaluating Anti Cancer Stem Cell Activity of Pre-operative Bevacizumab in Combination With Chemotherapy in Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 75
- 试验地点
- 3
- 主要终点
- Measure of the anti-cancer stem cell activity
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
WITH 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.
干预措施: bevacizumab (Drug)
without 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.
干预措施: no bevacizumab (Drug)
结局指标
主要结局
Measure of the anti-cancer stem cell activity
时间窗: 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
次要结局
- Evaluation of the disease-free survival, recurrence-free survival and overall survival(5 years)
- Evaluation of the safety of the treatment(8 months)
- Evaluation of the pathological complete response rate(8 months)