Phase II Study Evaluating the Efficacy and Tolerance of Bevacizumab (Avastin) in HER2- Inflammatory Breast Cancer
18 Years
N/A
Both
Breast Cancer
Trial Information
Phase II Study Evaluating the Efficacy and Tolerance of Bevacizumab (Avastin) in HER2- Inflammatory Breast Cancer
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.
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
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Complete histologic response rate
Outcome Time Frame:
Post surgery
Safety Issue:
No
Principal Investigator
Patrice Viens, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Institut Paoli-Calmettes
Authority:
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Study ID:
PACS09 UC-0140/0802
NCT ID:
NCT00820547
Start Date:
January 2009
Completion Date:
September 2015
Related Keywords:
- Breast Cancer
- inflammatory breast cancer
- stage IIIA breast cancer
- stage IIIB breast cancer
- stage IIIC breast cancer
- male breast cancer
- HER2-negative breast cancer
- Breast Neoplasms
- Inflammatory Breast Neoplasms
Name | Location |
|---|
