Clinical trial NCT01190345: Anti Cancer Stem Cell Activity of Pre-operative Bevacizumab and Chemotherapy in Breast Cancer
Official title: Phase II" Proof of Concept " Trial Evaluating Anti Cancer Stem Cell Activity of Pre-operative Bevacizumab in Combination With Chemotherapy in Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: breast cancer
Lead sponsor: Institut Paoli-Calmettes
Sponsor class: OTHER
First posted: 2010-08-27
Enrollment: 75
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Measure of the anti-cancer stem cell activity
timeFrame: 4 months
Secondary outcomes:
measure: Evaluation of the safety of the treatment
timeFrame: 8 months
measure: Evaluation of the disease-free survival, recurrence-free survival and overall survival
timeFrame: 5 years
measure: Evaluation of the pathological complete response rate
timeFrame: 8 months
Other outcomes:
Locations:
city: Marseille
country: France
facility: Jean-Marc EXTRA, MD
city: Paris
country: France
facility: Jean-Yves PIERGA
city: Reims
country: France
facility: Hervé CURE
Study officials:
affiliation: Institut Paoli-Calmettes
name: Jean-Marc EXTRA, MD
role: PRINCIPAL_INVESTIGATOR
References: