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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. Bevacizumab also may stop the growth of breast cancer by blocking blood flow to the tumor. Drugs used in chemotherapy, such as doxorubicin hydrochloride liposome, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving bevacizumab together with doxorubicin hydrochloride liposome may kill more tumor cells.
PURPOSE: This phase II trial is studying the side effects and how well giving bevacizumab together with doxorubicin hydrochloride liposome works in treating women with locally recurrent or metastatic breast cancer.
Full description
OBJECTIVES:
Primary
Secondary
OUTLINE: This is a multicenter study.
Patients receive bevacizumab IV over 30-90 minutes and doxorubicin hydrochloride liposome IV over 30-90 minutes on days 1 and 15. Treatment repeats every 4 weeks for up to 6 courses*. Patients then receive bevacizumab alone IV over 30-90 minutes on days 1 and 15. Courses with bevacizumab repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
NOTE: *Patients may receive additional courses of doxorubicin hydrochloride liposome at the discretion of the primary investigator.
Blood samples are collected at baseline, on day 1 of course 3 and then once every 3 months during study treatment, and after completion of study treatment. Samples are analyzed by enzyme-linked immunosorbent assay to determine the level of circulating angiogenesis-related molecules, including serum vascular endothelial growth factor (VEGF), VEGF receptor 1, and matrix metalloproteinase 9.
After completion of study treatment, patients are followed periodically.
PROJECTED ACCRUAL: A total of 43 patients will be accrued for this study.
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Inclusion and exclusion criteria
DISEASE CHARACTERISTICS:
Cytologically or histologically confirmed breast cancer
Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan
ErbB2-negative disease by immunohistochemistry (negative or 1+) or fluorescent in situ hybridization (FISH)
No known CNS metastases, even if previously treated
Hormone receptor status not specified
PATIENT CHARACTERISTICS:
Female
Menopausal status not specified
WHO performance status 0-1
LVEF ≥ 55%
Hemoglobin ≥ 10.0 g/dL
Absolute neutrophil count ≥ 1,500/mm³
Platelet count ≥ 100,000/mm³
Bilirubin < 2 times upper limit of normal (ULN)
ALT ≤ 2.5 times ULN (5 times ULN if liver metastases are present)
Alkaline phosphatase (AP) ≤ 2.5 times ULN
Creatinine ≤ 1.5 times ULN
Proteinuria < 2+ by dipstick OR protein ≤ 1 g/24hr-urine collection
INR ≤ 1.5 OR Quick ≥ 70%
aPTT ≤ 1.5 times ULN
No peripheral neuropathy > grade 2
No history or evidence of hereditary bleeding diathesis or coagulopathy with the risk of bleeding
No uncontrolled hypertension, defined as systolic blood pressure (BP) > 150 mm Hg and/or diastolic BP > 100 mm Hg, measured repeatedly at > 2 visits despite adequate treatment with ≥ 2 different antihypertensive drugs
No clinically significant cardiovascular disease, including the following:
No serious nonhealing wound, active peptic ulcer, nonhealing bone fracture, or bleeding skin metastases
No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months
No active infection requiring IV antibiotics
No known hypersensitivity to any of the study drugs or excipients
No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies
No evidence of any other disease that contraindicates the use of an investigational drug, that may affect patient compliance with study routines, or places the patient at high risk for treatment-related complications including, but not limited to, the following:
No known CNS disease unrelated to cancer (e.g., uncontrolled seizures), unless adequately treated with standard medical therapy
No high-risk factors for bleeding, including the following:
No other malignancy within the past 5 years except for adequately treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix
No significant traumatic injury within the past 28 days
No known HIV positivity
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for 12 months after completion of study therapy
PRIOR CONCURRENT THERAPY:
No prior chemotherapy for metastatic or inoperable locally recurrent breast cancer
No prior bevacizumab or other anti-vascular endothelial growth factor drug therapy
No prior radiotherapy involving the heart (usual irradiation dose to breast or chest wall allowed)
More than 12 months since prior neoadjuvant or adjuvant chemotherapy
No neoadjuvant or adjuvant doxorubicin hydrochloride with cumulative dose > 360 mg/m² or epirubicin hydrochloride with cumulative dose > 720 mg/m²
More than 6 months since prior adjuvant radiotherapy
More than 28 days since prior major surgical procedure with high risk of bleeding
More than 24 hours since prior minor surgical procedures
More than 10 days since prior acetylsalicylic acid (> 325 mg/day) or clopidogrel bisulfate (> 75 mg/day)
More than 10 days since prior and no concurrent use of full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic purposes
More than 30 days since prior investigational therapies or participation in other investigational studies
No concurrent hormonal therapy
No other concurrent antineoplastic or antitumor therapy
No other concurrent investigational drugs
No concurrent radiotherapy
No concurrent nonsteroidal anti-inflammatory drugs with activity on platelets and gastric mucosa (e.g., dipyridamole, clopidogrel bisulfate, acetylsalicylic acid)
No anticipated need for major surgery during the course of the study treatment
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Data sourced from clinicaltrials.gov
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