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

NCT01190345 | Completed Phase 2

• 1 other identifier: AVASTEM/IPC 2009-001
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 3

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

Keywords

breast cancer

Outcome Measures

Primary Outcomes (1)

• Measure of the anti-cancer stem cell activity

  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

  4 months

Secondary Outcomes (3)

• Evaluation of the safety of the treatment

  8 months

• Evaluation of the disease-free survival, recurrence-free survival and overall survival

  5 years

• Evaluation of the pathological complete response rate

  8 months

Study Arms (2)

WITH bevacizumab

EXPERIMENTAL

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.

Drug: bevacizumab

without bevacizumab

ACTIVE COMPARATOR

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.

Drug: no bevacizumab

Interventions

bevacizumab DRUG

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

Also known as: avastin

WITH bevacizumab

no bevacizumab DRUG

no bevacizumab

without bevacizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Institut Paoli-Calmettes: lead

Study Sites (3)

Jean-Marc EXTRA, MD

Marseille, 13009, France

Location

Jean-Yves PIERGA

Paris, France

Location

Hervé CURE

Reims, France

Location

Related Links

• institut Paoli-Calmettes web site

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Bevacizumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Jean-Marc EXTRA, MD

  Institut Paoli-Calmettes

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 24, 2010
• First Posted: August 27, 2010
• Study Start: May 1, 2010
• Primary Completion: July 24, 2012
• Study Completion: October 6, 2017
• Last Updated: August 13, 2018

Record last verified: 2018-08

Locations

FR (3)