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

NCT ID: NCT01190345

Last Updated: 2018-08-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 75 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-05-31
• Study Completion Date: 2017-10-06

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.

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

bevacizumab

Intervention Type: DRUG

Patients receive on day 1 of each cycle : bevacizumab 15 mg/kg (8 injections in total).

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.

Group Type: ACTIVE_COMPARATOR

no bevacizumab

Intervention Type: DRUG

no bevacizumab

Interventions

bevacizumab

Patients receive on day 1 of each cycle : bevacizumab 15 mg/kg (8 injections in total).

Intervention Type: DRUG

no bevacizumab

no bevacizumab

Intervention Type: DRUG

Other Intervention Names

avastin

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Institut Paoli-Calmettes

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jean-Marc EXTRA, MD

Role: PRINCIPAL_INVESTIGATOR

Institut Paoli-Calmettes

Locations

Jean-Marc EXTRA, MD

Marseille, , France

Jean-Yves PIERGA

Paris, , France

Hervé CURE

Reims, , France

Countries

France

Related Links

http://www.institutpaolicalmettes.fr/

institut Paoli-Calmettes web site

Other Identifiers

AVASTEM/IPC 2009-001

Identifier Type: -

Identifier Source: org_study_id