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

NCT ID: NCT00820547

Last Updated: 2019-10-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-01-31
• Study Completion Date: 2019-09-30

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.

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

(FEC / Docetaxel) + Bevacizumab

Neoadjuvant treatment: 4 cycles FEC + Bevacizumab followed by 4 cycles Docetaxel + Bevacizumab Adjuvant: Bevacizumab for 1 year

Group Type: EXPERIMENTAL

bevacizumab

Intervention Type: BIOLOGICAL

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

cyclophosphamide

Intervention Type: DRUG

Neoadjuvant: 500 mg/m2 d1 q3w, 4 cycles

docetaxel

Intervention Type: DRUG

Neoadjuvant: 100 mg/m2 q3w, 4 cycles

epirubicin hydrochloride

Intervention Type: DRUG

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

fluorouracil

Intervention Type: DRUG

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

Interventions

bevacizumab

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

Intervention Type: BIOLOGICAL

cyclophosphamide

Neoadjuvant: 500 mg/m2 d1 q3w, 4 cycles

Intervention Type: DRUG

docetaxel

Neoadjuvant: 100 mg/m2 q3w, 4 cycles

Intervention Type: DRUG

epirubicin hydrochloride

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

Intervention Type: DRUG

fluorouracil

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion 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

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

Sponsors

UNICANCER

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Patrice Viens, MD

Role: PRINCIPAL_INVESTIGATOR

Institut Paoli-Calmettes

Locations

Centre Paul Papin

Angers, , France

Institut Sainte Catherine

Avignon, , France

Centre Hospitalier Regional de Besancon - Hopital Jean Minjoz

Besançon, , France

Institut Bergonie

Bordeaux, , France

Polyclinique Bordeaux Nord Aquitaine

Bordeaux, , France

Centre Regional Francois Baclesse

Caen, , France

Centre Jean Perrin

Clermont-Ferrand, , France

Centre de Lutte Contre le Cancer Georges-Francois Leclerc

Dijon, , France

CMC Les Ormeaux

Le Havre, , France

Centre Oscar Lambret

Lille, , France

Centre Leon Berard

Lyon, , France

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

Marseille, , France

Centre Hospitalier General Andre Boulloche

Montbéliard, , France

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

Montpellier, , France

Centre Catherine de Sienne

Nantes, , France

Centre Antoine Lacassagne

Nice, , France

Institut Curie Hopital

Paris, , France

Institut Jean Godinot

Reims, , France

Centre Eugene Marquis

Rennes, , France

Centre Henri Becquerel

Rouen, , France

Clinique Armoricaine De Radiologie

Saint-Brieuc, , France

Centre Rene Huguenin

Saint-Cloud, , France

CRLCC Nantes - Atlantique

Saint-Herblain, , France

Centre Paul Strauss

Strasbourg, , France

Hopitaux Universitaire de Strasbourg

Strasbourg, , France

Institut Claudius Regaud

Toulouse, , France

Centre Alexis Vautrin

Vandœuvre-lès-Nancy, , France

Institut Gustave Roussy

Villejuif, , France

Countries

France

References

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.

Reference Type: DERIVED

PMID: 27032301 (View on PubMed)

Related Links

https://www.ncbi.nlm.nih.gov/pubmed/27032301

Abstract results

Other Identifiers

UNICANCER-PACS-09-0802

Identifier Type: OTHER

Identifier Source: secondary_id

2008-001807-53

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

PACS09 UC-0140/0802

Identifier Type: -

Identifier Source: org_study_id