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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Institut Paoli-Calmettes
ClinicalTrials.gov Identifier:
NCT01190345
First received: August 24, 2010
Last updated: March 19, 2013
Last verified: March 2013
  Purpose

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.


Condition Intervention Phase
Breast Cancer
Drug: bevacizumab
Drug: no bevacizumab
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Institut Paoli-Calmettes:

Primary Outcome Measures:
  • Measure of the anti-cancer stem cell activity [ Time Frame: 4 months ] [ Designated as safety issue: No ]
    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 Outcome Measures:
  • Evaluation of the safety of the treatment [ Time Frame: 8 months ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: 8 months ] [ Designated as safety issue: No ]
    Evaluation of the pathological complete response rate according to the classification of Sataloff


Estimated Enrollment: 75
Study Start Date: May 2010
Estimated Study Completion Date: May 2017
Estimated Primary Completion Date: May 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.

Drug: bevacizumab
Patients receive on day 1 of each cycle : bevacizumab 15 mg/kg (8 injections in total).
Other Name: avastin
Active Comparator: 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.

Drug: no bevacizumab
no bevacizumab

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01190345

Locations
France
Jean-Marc EXTRA, MD
Marseille, France, 13009
Jean-Yves PIERGA
Paris, France
Hervé CURE
Reims, France
Sponsors and Collaborators
Institut Paoli-Calmettes
Investigators
Principal Investigator: Jean-Marc EXTRA, MD Institut Paoli-Calmettes
  More Information

Additional Information:
No publications provided

Responsible Party: Institut Paoli-Calmettes
ClinicalTrials.gov Identifier: NCT01190345     History of Changes
Other Study ID Numbers: AVASTEM/IPC 2009-001
Study First Received: August 24, 2010
Last Updated: March 19, 2013
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Institut Paoli-Calmettes:
breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Bevacizumab
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 18, 2014