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

Breast Cancer Clinical Trial

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Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00820547
• Other study ID #: PACS09 UC-0140/0802
• Secondary ID: UNICANCER-PACS-0
• Status: Completed
• Phase: Phase 2
• Start date: January 2009
• Est. completion date: September 2019

Study information

• Verified date: October 2019
• Source: UNICANCER
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: September 2019
• Est. primary completion date: April 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

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
• docetaxel
Neoadjuvant: 100 mg/m2 q3w, 4 cycles
• epirubicin hydrochloride
Neoadjuvant: 100 mg/m2, d1 q3w, 4 cycles
• fluorouracil
Neoadjuvant: 500 mg/m2, d1 q3w, 4 cycles

Locations

Country	Name	City	State
France	Centre Paul Papin	Angers
France	Institut Sainte Catherine	Avignon
France	Centre Hospitalier Regional de Besancon - Hopital Jean Minjoz	Besancon
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	Montbeliard
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	Vandoeuvre-les-Nancy
France	Institut Gustave Roussy	Villejuif

Sponsors (1)

Lead Sponsor	Collaborator
UNICANCER

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete histologic response rate		Post surgery
Secondary	Progression-free survival		3 and 5 years
Secondary	Overall survival		3 and 5 years
Secondary	Toxicity as assessed by CTCAE v3.0		3 and 5 years
Secondary	Predictive factors of response to bevacizumab		3 and 5 years
Secondary	Circulating peripheral cells (circulating endothelial and tumor cells): correlation of initial rate and association with histological response after surgery		Post-surgery
Secondary	Genomic and proteomic analyses and correlation with histologic response		Post surgery

External Links

•   Abstract results