Phase II Trial of Fulvestrant and Bevacizumab in Patients With Metastatic Breast Cancer Previously Treated With an Aromatase Inhibitor
Phase II Trial of Fulvestrant and Bevacizumab in Patients With Metastatic Breast Cancer Previously Treated With an Aromatase Inhibitor
RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using fulvestrant may fight breast cancer by blocking the use of estrogen by the 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. Fulvestrant and bevacizumab may also stop the growth of breast cancer by blocking blood flow to the tumor. Giving fulvestrant together with bevacizumab may be an effective treatment for metastatic breast cancer.
PURPOSE: This phase II trial is studying how well giving fulvestrant together with bevacizumab works in treating patients with metastatic breast cancer.
OBJECTIVES:
Primary
Secondary
OUTLINE: This is a multicenter study.
Patients receive fulvestrant intramuscularly on day 1 and bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Quality of life is assessed at baseline, prior to every other course, and at the completion of study treatment.
After completion of study treatment, patients are followed every 3-6 months for 5 years.
PROJECTED ACCRUAL: A total of 51 patients will be accrued for this study.
DISEASE CHARACTERISTICS:
Histologically or cytologically confirmed breast cancer
Must have received an aromatase inhibitor (e.g., letrozole, anastrozole, or exemestane) in an adjuvant or metastatic setting
If tumor is HER2 positive (3+ by immunohistochemistry or amplified by fluorescent in situ hybridization) the patient must have received ≥ 1 prior trastuzumab (Herceptin®)-containing regimen unless there is a contraindication to trastuzumab
Measurable or nonmeasurable disease, including any of the following :
No microscopic residual disease only
Enrolled on or refused enrollment on clinical trial NCCTG-N0392
No evidence of active brain metastasis including leptomeningeal involvement
Hormone receptor status:
PATIENT CHARACTERISTICS:
Male or female
Female patients must be post-menopausal based on any 1 of the following criteria:
ECOG performance status 0-2
Life expectancy > 3 months
Fertile patients must use effective contraception during and for 30 days after completion of study treatment
WBC ≥ 3,000 mg/dL
Hemoglobin > 8 g/dL
Absolute neutrophil count > 1,000/mm³
Platelet count ≥ 100,000/mm³
Bilirubin ≤ 1.5 times upper limit of normal (ULN)
Alkaline phosphatase ≤ 2.5 times ULN
AST and ALT ≤ 2.5 times ULN
Creatinine ≤ 1.5 times ULN
Urine protein < 1+ OR < 1 g of protein by 24-hour urine collection
No uncontrolled hypertension (i.e., blood pressure [BP] > 160/90 mm Hg on ≥ 2 occasions at least 5 minutes apart)
No clinically significant cardiac disease, including any of the following:
No arterial or venous thrombosis within the past 12 months
No hemoptysis or gastrointestinal hemorrhage within the past 6 months
No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 4 weeks
No significant traumatic injury within the past 4 weeks
No active, unresolved infection
No history of hypertensive crisis or hypertensive encephalopathy
No history of bleeding diathesis or uncontrolled coagulopathy
No history of cerebrovascular accident, hemorrhage, or stroke
No allergy or hypersensitivity to drug product excipients, murine antibodies, or agents chemically similar to study drugs
No other malignancy within the past 3 years except for basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
No other serious medical condition that would preclude study therapy or compliance
PRIOR CONCURRENT THERAPY:
See Disease Characteristics
Prior radiotherapy to a target lesion allowed provided there has been clear progression since radiotherapy was completed
At least 4 weeks since prior radiotherapy
No more than 1 prior chemotherapy regimen for metastatic disease
No more than 2 prior endocrine (hormonal) therapy regimens in the neoadjuvant, adjuvant, or metastatic setting
At least 4 weeks since prior major surgery or open biopsy
At least 4 weeks since prior chemotherapy or immunologic therapy
At least 2 weeks since prior and no concurrent use of any of the following agents:
No concurrent treatment in another clinical study with investigational procedures or investigational therapies
No other concurrent anticancer therapy, including chemotherapy, biologic agents, or radiotherapy
No routine use of granulocyte colony-stimulating factors during course 1
No concurrent oprelvekin
Moline, Illinois 61265, United States
Ottawa, Illinois 61350, United States
Peoria, Illinois 61615, United States
Beech Grove, Indiana 46107, United States
Des Moines, Iowa 50309, United States
Des Moines, Iowa 50314, United States
Wichita, Kansas 67214, United States
Dearborn, Michigan 48123-2500, United States
Grosse Pointe Woods, Michigan 48236, United States
Minneapolis, Minnesota 55407, United States
Robbinsdale, Minnesota 55422-2900, United States
St Louis, Missouri 63141, United States
Billings, Montana 59101, United States
Missoula, Montana 59807, United States
Allentown, Pennsylvania 18105, United States
Wilkes-Barre, Pennsylvania 18711, United States
Sioux Falls, South Dakota 57117-5039, United States
Green Bay, Wisconsin 54301-3526, United States