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Breast CancerPhase 2Beverly1NCT00820547

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

A Phase 2 study testing bevacizumab, cyclophosphamide and docetaxel in people with Breast Cancer, run by UNICANCER at 28 sites in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Breast Cancer
What is being tested?
bevacizumab, cyclophosphamide and docetaxel
Could I receive a placebo?
No, everyone receives an active treatment
How many people
100 participants
Where
28 sitesFrance
Study dates
Jan 2009to Sep 2019
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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

Trial locations and contacts

28 sites in 1 country.

28 sites in 1 country

France28 sites

  • Centre Paul Papin

    Angers, 49036

  • Institut Sainte Catherine

    Avignon, 84000

  • Centre Hospitalier Regional de Besancon - Hopital Jean Minjoz

    Besançon, 25030

  • Institut Bergonie

    Bordeaux, 33076

  • Polyclinique Bordeaux Nord Aquitaine

    Bordeaux, 33300

  • Centre Regional Francois Baclesse

    Caen, 14076

  • Centre Jean Perrin

    Clermont-Ferrand, 63011

  • Centre de Lutte Contre le Cancer Georges-Francois Leclerc

    Dijon, 21079

  • CMC Les Ormeaux

    Le Havre, 76600

  • Centre Oscar Lambret

    Lille, 59020

  • Centre Leon Berard

    Lyon, 69373

  • Marseille Institute of Cancer - Institut J. Paoli and I. Calmettes

    Marseille, 13273

  • Centre Hospitalier General Andre Boulloche

    Montbéliard, 25209

  • Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle

    Montpellier, 34298

  • Centre Catherine de Sienne

    Nantes, 02

  • Centre Antoine Lacassagne

    Nice, 06189

  • Institut Curie Hopital

    Paris, 75248

  • Institut Jean Godinot

    Reims, 51056

  • Centre Eugene Marquis

    Rennes, 35042

  • Centre Henri Becquerel

    Rouen, 76038

  • Clinique Armoricaine De Radiologie

    Saint-Brieuc, F-22015

  • Centre Rene Huguenin

    Saint-Cloud, 92211

  • CRLCC Nantes - Atlantique

    Saint-Herblain, 44805

  • Centre Paul Strauss

    Strasbourg, 67065

  • Hopitaux Universitaire de Strasbourg

    Strasbourg, 67091

  • Institut Claudius Regaud

    Toulouse, 31052

  • Centre Alexis Vautrin

    Vandœuvre-lès-Nancy, 54511

  • Institut Gustave Roussy

    Villejuif, F-94805

Other trials in France

About this study

Official title: Phase II Study Evaluating the Efficacy and Tolerance of Bevacizumab (Avastin) in HER2- Inflammatory Breast Cancer

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.

Read the 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.

Conditions
Breast Cancer
Being tested
bevacizumab, cyclophosphamide, docetaxel, epirubicin hydrochloride, fluorouracil
Keywords
inflammatory breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer, male breast cancer, HER2-negative breast cancer
Medical subject headings
Breast Neoplasms, Inflammatory Breast Neoplasms, Breast Neoplasms, Male

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • bevacizumabBiological

    During neoadjuvant phase: 15 mg/kg, d1 q3w, 8 cycles During adjuvant phase:15 mg/kg, d1 q3w, 10 cycles

  • cyclophosphamideDrug

    Neoadjuvant: 500 mg/m2 d1 q3w, 4 cycles

  • docetaxelDrug

    Neoadjuvant: 100 mg/m2 q3w, 4 cycles

  • epirubicin hydrochlorideDrug

    Neoadjuvant: 100 mg/m2, d1 q3w, 4 cycles

  • fluorouracilDrug

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

Study groups in NCT00820547
Study groupRoleWhat they receive
(FEC / Docetaxel) + BevacizumabExperimentalNeoadjuvant treatment: 4 cycles FEC + Bevacizumab followed by 4 cycles Docetaxel + Bevacizumab Adjuvant: Bevacizumab for 1 year
Receives: Biological: bevacizumab; Drug: cyclophosphamide; Drug: docetaxel; Drug: epirubicin hydrochloride; Drug: fluorouracil

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Complete histologic response rate

    Measured: Post surgery

Secondary outcomes (6)

  1. Progression-free survival

    Measured: 3 and 5 years

  2. Overall survival

    Measured: 3 and 5 years

  3. Toxicity as assessed by CTCAE v3.0

    Measured: 3 and 5 years

  4. Predictive factors of response to bevacizumab

    Measured: 3 and 5 years

  5. Circulating peripheral cells (circulating endothelial and tumor cells): correlation of initial rate and association with histological response after surgery

    Measured: Post-surgery

  6. Genomic and proteomic analyses and correlation with histologic response

    Measured: Post surgery

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Jan 2009 (estimated)
  2. Study startJan 2009
  3. Primary completionApr 2015
  4. Study completionSep 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
100 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00820547
Sponsor's protocol ID
PACS09 UC-0140/0802
Other IDs
UNICANCER-PACS-09-0802, 2008-001807-53, 2008
Acronym
Beverly1
Status last verified
Oct 2019
First submitted
9 Jan 2009
Last updated
22 Oct 2019
Results posted
No
Data monitoring committee
Yes
Individual data sharing
Yes: Unicancer will share de-identified individual data that underlie the results reported under the following conditions: the data shared will be limit to that required for independent mandated verification of the published results, the applicant will need authorization from Unicancer for personal access, and data will only be transferred after signing of a data access agreement. A decision concerning the sharing of other study documents, including protocol and statistical analysis plan will be examined upon request.

Publications

  • Bertucci F, Fekih M, Autret A, Petit T, Dalenc F, Levy C, Romieu G, Bonneterre J, Ferrero JM, Kerbrat P, Soulie P, Mouret-Reynier MA, Bachelot T, Lerebours F, Eymard JC, Deblock M, Lortholary A, Hardy-Bessard AC, Barthelemy P, Bonnefoi H, Charafe-Jauffret E, Bidard FC, Viens P, Lemonnier J, Pierga JY. Bevacizumab plus neoadjuvant chemotherapy in patients with HER2-negative inflammatory breast cancer (BEVERLY-1): a multicentre, single-arm, phase 2 study. Lancet Oncol. 2016 May;17(5):600-11. doi: 10.1016/S1470-2045(16)00011-5. Epub 2016 Mar 28.

    PubMed 27032301

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing bevacizumab, cyclophosphamide and docetaxel in people with Breast Cancer, run by UNICANCER at 28 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 28 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Complete histologic response rate (time frame: Post surgery). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00820547, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Oct 2019.

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