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About
RATIONALE: 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 more than one drug (combination chemotherapy) may kill more tumor cells. 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. Bevacizumab may also stop the growth of breast cancer by blocking blood flow to the tumor. Giving chemotherapy and bevacizumab before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving bevacizumab after surgery may kill any tumor cells that remain after surgery. It is not yet known which chemotherapy regimen is more effective with or without bevacizumab in treating breast cancer.
PURPOSE: This randomized phase III trial is studying six different chemotherapy regimens to compare how well they work with or without bevacizumab in treating women with stage I, stage II, or stage IIIA breast cancer that can be removed by surgery.
Full description
OBJECTIVES:
Primary
Secondary
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to tumor size (2-4 cm vs > 4 cm), nodal status (negative vs positive), hormone receptor status (estrogen receptor [ER]-positive and/or progesterone-receptor [PgR]-positive vs ER- and PgR-negative), and age (< 50 years vs ≥ 50 years). Patients are randomized to 1 of 6 treatment arms.
Core needle biopsies are performed at baseline. Tumor tissue samples are also collected during definitive surgery. Samples are examined for gene expression and polymorphism by reverse transcriptase-polymerase chain reaction analysis and chemoresponse assay (ChemoFx®).
After completion of study therapy, patients are followed periodically for 10 years.
PROJECTED ACCRUAL: A total of 1,200 patients will be accrued for this study.
Enrollment
Sex
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Volunteers
Inclusion criteria
The patient must have consented to participate and must have signed and dated an appropriate Institutional Review Board (IRB)-approved consent form that conforms to federal and institutional guidelines for the study treatment and submission of pre-entry core biopsy material for correlative studies.
Patients must be female.
Patients must be 18 years of age or older.
Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
The diagnosis of invasive adenocarcinoma of the breast must have been made by core needle biopsy.
The primary breast tumor must be palpable and measure greater than or equal to 2.0 cm on physical exam.
All patients must have their left ventricular ejection fraction (LVEF) assessed by multigated acquisition (MUGA) scan or echocardiogram within 3 months prior to study entry. The LVEF must be greater than or equal to the lower limit of normal (LLN) for the cardiac imaging facility performing the study. Note: If the cardiac imaging facility cannot provide a LLN, use 50% as the LLN value.
All patients must have an EKG within 3 months prior to study entry.
At the time of randomization:
Patients with either skeletal pain or alkaline phosphatase that is greater than ULN but less than or equal 2.5 x ULN are eligible for inclusion in the study if bone scans do not demonstrate metastatic disease. Suspicious findings on bone scan must be confirmed as benign by x-ray, MRI, or biopsy.
Patients with AST or alkaline phosphatase greater than ULN are eligible for inclusion in the study if liver imaging does not demonstrate metastatic disease and adequate bone marrow and liver function results as described above are met.
The following criteria for evidence of adequate renal function must be met:
Serum creatinine less than or equal ULN for the lab.
Calculated creatinine clearance must be greater than 50 mL/min.
Urine protein/urine creatinine (UPC) ratio must be less than 1.0.
Patient must be able to swallow oral medications.
Exclusion criteria
Tumor determined to be strongly human epidermal growth factor receptor 2 (HER2)-positive by immunohistochemistry (3+) or by fluorescent in situ hybridization (positive for gene amplification).
Excisional or incisional biopsy for this primary breast tumor.
Surgical axillary staging procedure prior to study entry. Exceptions: 1) Fine Needle Aspiration (FNA) or core biopsy of an axillary node is permitted for any patient, and 2) although not recommended, a pre-neoadjuvant therapy sentinel lymph node biopsy for patients with clinically negative axillary nodes is permitted.
Tumors clinically staged as T4.
Ipsilateral cN2b or cN3 disease. (Patients with cN1 or cN2a disease are eligible.)
Definitive clinical or radiologic evidence of metastatic disease.
Synchronous bilateral breast cancer (invasive or DCIS).
Treatment including radiation therapy, chemotherapy, biotherapy, and/or hormonal therapy for the currently diagnosed breast cancer prior to study entry.
Any sex hormonal therapy, e.g., birth control pills, ovarian hormonal replacement therapy, etc. (These patients are eligible if this therapy is discontinued prior to randomization.)
Therapy with any hormonal agent such as raloxifene, tamoxifen, or other selective estrogen receptor modulator (SERM), either for osteoporosis or breast cancer prevention. (Patients are eligible only if these medications are discontinued prior to randomization.)
Prior history of breast cancer, including DCIS. (Patients with a history of lobular carcinoma in situ [LCIS] are eligible.)
Prior therapy with anthracyclines, taxanes, capecitabine, 5-FU (fluorouracil), gemcitabine, or bevacizumab for any malignancy.
Other malignancies unless the patient is considered to be disease-free for 5 or more years prior to randomization and is deemed by her physician to be at low risk for recurrence. Patients with the following cancers are eligible if diagnosed and treated within the past 5 years: carcinoma in situ of the cervix, carcinoma in situ of the colon, melanoma in situ, and basal cell and squamous cell carcinoma of the skin.
Cardiac disease that would preclude the use of anthracyclines. This includes:
History of myocardial infarction documented by elevated cardiac enzymes or persistent regional wall abnormalities on assessment of LV function.
History of transient ischemic attack (TIA) or cerebrovascular accident (CVA).
History of other arterial thrombotic event within 12 months before study entry.
Symptomatic peripheral vascular disease.
Any significant non-traumatic bleeding within 6 months before study entry.
Serious or non-healing wound, skin ulcers, or incompletely healed bone fracture.
Gastroduodenal ulcer(s) determined by endoscopy to be active.
Invasive procedures defined as follows:
Known bleeding diathesis or coagulopathy. (Patients on warfarin with an in-range international normalized ratio [INR] [usually between 2 and 3] are eligible.)
Sensory/motor neuropathy greater than or equal grade 2, as defined by the NCI's Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE v3.0).
Other non-malignant systemic disease (cardiovascular, renal, hepatic, etc.) that would preclude treatment with any of the treatment regimens or would prevent required follow-up.
Conditions that would prohibit administration of corticosteroids.
History of severe hypersensitivity reaction to drugs formulated with polysorbate 80.
Administration of any investigational agents within 30 days before study entry.
Pregnancy or lactation at the time of proposed randomization.
Primary purpose
Allocation
Interventional model
Masking
1,206 participants in 6 patient groups
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Data sourced from clinicaltrials.gov
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