ClinicalTrials.gov
ClinicalTrials.gov Menu

Efficacy and Tolerance Study of Bevacizumab in Her2- Inflammatory Breast Cancer Patients (Beverly1)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00820547
Recruitment Status : Active, not recruiting
First Posted : January 12, 2009
Last Update Posted : October 15, 2018
Sponsor:
Information provided by (Responsible Party):
UNICANCER

Brief Summary:

RATIONALE: Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving bevacizumab and combination chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving bevacizumab and radiation therapy after surgery may kill any tumor cells that remain after surgery.

PURPOSE: This phase II trial is studying giving bevacizumab together with chemotherapy before surgery and bevacizumab and radiation therapy after surgery to see how well it works in treating patients with inflammatory breast cancer.


Condition or disease Intervention/treatment Phase
Breast Cancer Biological: bevacizumab Drug: cyclophosphamide Drug: docetaxel Drug: epirubicin hydrochloride Drug: fluorouracil Phase 2

Detailed Description:

OBJECTIVES:

Primary

  • Evaluate the complete histological response rate in patients with inflammatory HER2-negative breast cancer treated with bevacizumab and concurrent chemotherapy followed by bevacizumab and concurrent hormonal therapy after surgery and radiotherapy.

Secondary

  • Evaluate the progression-fee and overall survival of these patients at 3 and 5 years.
  • Evaluate the tolerance of bevacizumab in these patients.
  • Assess circulating metastatic disease before, during, and after treatment.
  • Assess circulating endothelial cells before, during, and after treatment.
  • Assess predictive factors of response by genomic and proteomic studies on frozen tumor samples and fluid samples (i.e., serum and plasma).

OUTLINE: This is a multicenter study.

  • Neoadjuvant induction therapy:

    • Courses 1-4: Patients receive bevacizumab IV over 30-90 minutes, fluorouracil IV, epirubicin hydrochloride IV over 10 minutes, and cyclophosphamide IV over 5 minutes on day 1.
    • Courses 5-8: Patients receive bevacizumab IV over 30-90 minutes and docetaxel IV over 1 hour on day 1.

Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity.

  • Surgery: Patients undergo surgery 4-6 weeks after completion of bevacizumab.
  • Adjuvant therapy: Beginning 2-4 weeks after surgery, patients undergo radiotherapy for 6 weeks. Patients also receive bevacizumab IV over 30-90 minutes beginning 2-4 weeks after surgery, during the radiotherapy period. Treatment with bevacizumab repeats every 3 weeks for 30 weeks in the absence of disease progression or unacceptable toxicity. Patients who are estrogen receptor- or progesterone receptor-positive (≥ 10% by IHC) receive the following concurrent hormonal therapy beginning in week 7:

    • Premenopausal patients: Patients receive tamoxifen citrate for 5 years.
    • Postmenopausal patients: Patients receive aromatase-inhibitor therapy (or tamoxifen citrate if unable to tolerate anti-aromatase therapy) for 5 years.
    • Perimenopausal patients: Patients receive tamoxifen citrate for 2-3 years and aromatase-inhibitor therapy for 2-3 years OR tamoxifen citrate for 5 years followed by aromatase-inhibitor therapy for 2-3 years (if follicle-stimulating hormone > 30 IU/L and/or estradiol < 30 ng/L).

After completion of study treatment, patients are followed for at least 3 years.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 100 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study Evaluating the Efficacy and Tolerance of Bevacizumab (Avastin) in HER2- Inflammatory Breast Cancer
Actual Study Start Date : January 2009
Actual Primary Completion Date : April 2015
Estimated Study Completion Date : December 2018


Arm Intervention/treatment
Experimental: (FEC / Docetaxel) + Bevacizumab
Neoadjuvant treatment: 4 cycles FEC + Bevacizumab followed by 4 cycles Docetaxel + Bevacizumab Adjuvant: Bevacizumab for 1 year
Biological: bevacizumab
During neoadjuvant phase: 15 mg/kg, d1 q3w, 8 cycles During adjuvant phase:15 mg/kg, d1 q3w, 10 cycles

Drug: cyclophosphamide
Neoadjuvant: 500 mg/m2 d1 q3w, 4 cycles

Drug: docetaxel
Neoadjuvant: 100 mg/m2 q3w, 4 cycles

Drug: epirubicin hydrochloride
Neoadjuvant: 100 mg/m2, d1 q3w, 4 cycles

Drug: fluorouracil
Neoadjuvant: 500 mg/m2, d1 q3w, 4 cycles




Primary Outcome Measures :
  1. Complete histologic response rate [ Time Frame: Post surgery ]

Secondary Outcome Measures :
  1. Progression-free survival [ Time Frame: 3 and 5 years ]
  2. Overall survival [ Time Frame: 3 and 5 years ]
  3. Toxicity as assessed by CTCAE v3.0 [ Time Frame: 3 and 5 years ]
  4. Predictive factors of response to bevacizumab [ Time Frame: 3 and 5 years ]
  5. Circulating peripheral cells (circulating endothelial and tumor cells): correlation of initial rate and association with histological response after surgery [ Time Frame: Post-surgery ]
  6. Genomic and proteomic analyses and correlation with histologic response [ Time Frame: Post surgery ]


Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed inflammatory breast cancer, meeting 1 of the following staging criteria:

    • T4d, any N (AJCC stage IIIB or IIIC)
    • Gustave-Roussy Institute (IGR) classification Poussee evolutirie (PEV; measures tumor growth over time) 2

      • PEV 2: tumor with underlying breast tissue, especially skin, that is affected by subacute inflammation and edema involving < ½ of breast surface
    • IGR classification PEV 3

      • PEV 3: acute or subacute inflammation and edema involving > ½ of breast surface
    • Biopsy-confirmed presence of tumor embolism in surface lymph nodes
  • HER2-negative (HER2 0 or 1+, or HER2 2+ by IHC if FISH-negative allowed)
  • No metastatic disease
  • No non-inflammatory breast cancer with edema, ulceration, or satellite skin nodules
  • No bilateral breast cancer
  • Hormone receptor status known

PATIENT CHARACTERISTICS:

  • Any menopausal status allowed
  • WHO performance status 0-2
  • Life expectancy ≥3 months
  • LVEF normal by ECHO
  • ANC >1.5 x 10^9/L
  • Platelet count >100 x 10^9/L
  • INR ≤1.5 (except for patients on prophylactic anticoagulants)
  • aPTT ≤1.5 times upper limit of normal (ULN)
  • Total bilirubin normal
  • SGOT and SGPT ≤1.25 times ULN
  • Alkaline phosphatase ≤2.5 times ULN
  • Creatinine clearance ≥60 mL/min
  • Proteinuria <2+ or 24-hour urine protein ≤1 g
  • No unhealed wound, stomach ulcer, or bone fracture
  • No history of thrombotic or hemorrhagic disorders
  • No significant cardiovascular disease including the following:

    • Cerebrovascular accident within the past 6 months
    • Unstable angina
    • Cardiac failure
    • Myocardial infarction
    • Arrhythmia requiring treatment
  • No uncontrolled hypertension (i.e., systolic BP >150 mm Hg and/or diastolic BP >100 mm Hg)
  • No other active infection or serious illness that would preclude patient from receiving study treatment
  • No hypersensitivity to any active products or excipients of study drugs
  • Not pregnant or nursing
  • Fertile patients must use effective contraception during and for 6 months after completion of study treatment
  • No social or psychologic reasons that would prevent study compliance or follow-up
  • No patients who are incarcerated or on probation

PRIOR CONCURRENT THERAPY:

  • No prior chemotherapy, radiotherapy, or hormonal therapy for this disease
  • More than 4 weeks since prior surgery (diagnostic biopsy or installation of implant allowed)
  • More than 10 days since prior chronic non-inflammatory steroids (e.g., acetylsalicylic acid >325 mg/day) or platelet anticoagulation treatment (e.g., dipyridamole, ticlopidine, clodiprogel, cilostazol)
  • More than 10 days since prior oral or parenteral anticoagulant or thrombolytic drugs (preventative thrombolytic drugs allowed)
  • No concurrent participation in another experimental clinical trial

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00820547


Locations
France
Centre Paul Papin
Angers, France, 49036
Institut Sainte Catherine
Avignon, France, 84000
Centre Hospitalier Regional de Besancon - Hopital Jean Minjoz
Besancon, France, 25030
Institut Bergonie
Bordeaux, France, 33076
Polyclinique Bordeaux Nord Aquitaine
Bordeaux, France, 33300
Centre Regional Francois Baclesse
Caen, France, 14076
Centre Jean Perrin
Clermont-Ferrand, France, 63011
Centre de Lutte Contre le Cancer Georges-Francois Leclerc
Dijon, France, 21079
CMC Les Ormeaux
Le Havre, France, 76600
Centre Oscar Lambret
Lille, France, 59020
Centre Leon Berard
Lyon, France, 69373
Marseille Institute of Cancer - Institut J. Paoli and I. Calmettes
Marseille, France, 13273
Centre Hospitalier General Andre Boulloche
Montbeliard, France, 25209
Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle
Montpellier, France, 34298
Centre Catherine de Sienne
Nantes, France, 02
Centre Antoine Lacassagne
Nice, France, 06189
Institut Curie Hopital
Paris, France, 75248
Institut Jean Godinot
Reims, France, 51056
Centre Eugene Marquis
Rennes, France, 35042
Centre Henri Becquerel
Rouen, France, 76038
Clinique Armoricaine De Radiologie
Saint Brieuc, France, F-22015
Centre Rene Huguenin
Saint Cloud, France, 92211
CRLCC Nantes - Atlantique
Saint-Herblain, France, 44805
Centre Paul Strauss
Strasbourg, France, 67065
Hopitaux Universitaire de Strasbourg
Strasbourg, France, 67091
Institut Claudius Regaud
Toulouse, France, 31052
Centre Alexis Vautrin
Vandoeuvre-les-Nancy, France, 54511
Institut Gustave Roussy
Villejuif, France, F-94805
Sponsors and Collaborators
UNICANCER
Investigators
Principal Investigator: Patrice Viens, MD Institut Paoli-Calmettes

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: UNICANCER
ClinicalTrials.gov Identifier: NCT00820547     History of Changes
Other Study ID Numbers: PACS09 UC-0140/0802
UNICANCER-PACS-09-0802 ( Other Identifier: Internal Id Number )
2008-001807-53 ( EudraCT Number )
First Posted: January 12, 2009    Key Record Dates
Last Update Posted: October 15, 2018
Last Verified: October 2018

Keywords provided by UNICANCER:
inflammatory breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer
male breast cancer
HER2-negative breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Inflammatory Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Bevacizumab
Docetaxel
Cyclophosphamide
Fluorouracil
Epirubicin
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Antimetabolites
Antimetabolites, Antineoplastic
Antibiotics, Antineoplastic