Intervention: Fulvestrant
Trial phase: Phase 2
ATC code: L02BA03
SMILES: [H][C@@]12CC[C@H](O)[C@@]1(C)CC[C@]1([H])c3ccc(O)cc3C[C@@H](CCCCCCCCCS(=O)CCCC(F)(F)C(F)(F)F)[C@@]21[H]
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 33
Group description: Patients receive Fulvestrant 250 mg intramuscularly every 28 days and Bevacizumab 10mg/kg intravenously with a rate-regulating device on days 1 and 15. Loading dose of fulvestrant for the first cycle will consist of an extra 250 mg on day 1 (for total of 500 mg Cycle 1, Day 1). The initial bevacizumab dose will be delivered over 90 minutes. If the first infusion is tolerated without infusion-associated adverse events (fever and/or chills), the second infusion may be delivered over 60 minutes. If the 60-minute infusion is well-tolerated, all subsequent infusions may be delivered over 30 minutes.Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Eligibility criteria:
DISEASE CHARACTERISTICS:

Histologically or cytologically confirmed breast cancer

Metastatic disease
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 :

Bone metastasis
Pleural/pericardial effusion
Ascites
Inflammatory skin changes
No microscopic residual disease only
Enrolled on or refused enrollment on clinical trial NCCTG-N0392

No evidence of active brain metastasis including leptomeningeal involvement

CNS metastasis controlled (i.e., at least 2 months of no symptoms or evidence of progression) by prior surgery and/or raditherapy are allowed

Hormone receptor status:

Estrogen and/or progesterone receptor-positive tumor

PATIENT CHARACTERISTICS:

Male or female

Female patients must be post-menopausal based on any 1 of the following criteria:

Age ≥ 60 years
Age ≥ 45 years with last menstrual period ≥ 12 months prior to study entry
Estradiol and follicle-stimulating hormone levels in postmenopausal range
History of bilateral oophorectomy
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 nephrotic syndrome

No uncontrolled hypertension (i.e., blood pressure [BP] > 160/90 mm Hg on ≥ 2 occasions at least 5 minutes apart)

Patients who have recently started or adjusted antihypertensive medications are eligible provided BP is < 140/90 mm Hg on any new regimen for ≥ 3 different observations in ≥ 14 days

No clinically significant cardiac disease, including any of the following:

Congestive heart failure
Symptomatic coronary artery disease
Unstable angina
Cardiac arrhythmias not well controlled with medication
Myocardial infarction within the past 12 months
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

Single-dose radiation for palliation or to a nontarget lesion only allowed within the past 4 weeks
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:

Aspirin (daily low-dose [81 mg] aspirin allowed])
Thrombolytic agents
Anticoagulants (low-dose anticoagulation therapy to maintain patency of a vascular access device is allowed)
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