Erlotinib and Bevacizumab in Treating Women With Stage IV Breast Cancer

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed carcinoma of the breast

  • Metastatic (stage IV) disease

• Stable or progressive disease on or after at least 1 but no more than 2 prior conventional chemotherapy regimens for metastatic breast cancer

  • Prior high-dose chemotherapy with autologous stem cell or bone marrow transplantation is considered 1 prior regimen when administered for metastatic disease
  • Prior adjuvant chemotherapy and/or hormonal therapy allowed, and do not count as prior therapy
• Prior trastuzumab (Herceptin) required for HER2/neu-positive patients (3+ by immunohistochemistry or positive by fluorescent in situ hybridization [FISH])

• Unidimensionally measurable disease

  • At least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan
• No prior or concurrent brain metastases or primary brain tumor, as documented by CT scan or MRI

• Hormone receptor status:

  • Not specified

PATIENT CHARACTERISTICS:

Age

• 18 and over

Sex

• Male or female

Menopausal status

• Not specified

Performance status

• ECOG 0-2 OR
• Karnofsky 60-100%

Life expectancy

• More than 3 months

Hematopoietic

• WBC ≥ 3,000/mm^3
• Absolute neutrophil count ≥ 1,000/mm^3
• Platelet count ≥ 75,000/mm^3
• AST/ALT ≤ 2.5 times upper limit of normal
• No bleeding diathesis
• No coagulopathy

Hepatic

• Bilirubin normal
• AST/ALT ≤ 2.5 times upper limit of normal
• INR < 1.5 (for patients receiving warfarin)

Renal

• Creatinine normal OR
• Creatinine clearance ≥ 60 mL/min
• No grade 1 or greater proteinuria OR
• Urinary protein ≤ 500 mg/24 hours

Cardiovascular

• Ejection fraction normal by MUGA or echocardiogram
• No history of stroke
• No clinically significant cardiovascular disease (e.g., uncontrolled hypertension, myocardial infarction, unstable angina pectoris)
• No New York Heart Association class II-IV heart disease
• No symptomatic congestive heart failure
• No serious cardiac arrhythmia requiring medication
• No grade II or greater peripheral vascular disease within the past year
• No transient ischemic attack within the past 6 months
• No cerebrovascular accident within the past 6 months
• No unstable angina within the past 6 months
• No myocardial infarction within the past 6 months
• No clinically significant peripheral artery disease within the past 6 months
• No other arterial thrombotic event within the past 6 months

Ophthalmologic

• No abnormalities of the cornea (e.g., dry eye syndrome or Sjögren's syndrome)
• No congenital ophthalmologic abnormality (e.g., Fuch's dystrophy)
• No abnormal slit-lamp examination using a vital dye (e.g., fluorescein or Bengal-Rose)
• No abnormal corneal sensitivity test (Schirmer test or similar tear production test)

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective barrier contraception
• No significant traumatic injury within the past 28 days
• No prior allergic reaction attributed to compounds of similar chemical or biological composition to erlotinib or bevacizumab
• No history of seizures not controlled with standard medical therapy
• No serious non-healing wound, ulcer, or bone fracture
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study compliance
• No other concurrent uncontrolled illness
• No gastrointestinal tract disease requiring IV alimentation
• Able to take oral medication

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Disease Characteristics
• More than 3 weeks since prior immunotherapy
• No prior cetuximab

Chemotherapy

• See Disease Characteristics
• More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
• No lifetime cumulative doxorubicin dose > 450 mg/m^2
• No lifetime cumulative epirubicin dose > 700 mg/m^2
• No lifetime cumulative doxorubicin HCl liposome dose > 550 mg/m^2
• No lifetime cumulative mitoxantrone dose > 140 mg/m^2

Endocrine therapy

• See Disease Characteristics
• More than 2 weeks since prior hormonal therapy

Radiotherapy

• More than 3 weeks since prior radiotherapy

Surgery

• More than 28 days since prior major surgery or open biopsy
• No prior surgery affecting gastrointestinal absorption

Other

• More than 3 weeks since prior investigational therapy
• No prior kinase insert domain-containing receptor (KDR) inhibitors (e.g., VEGF Trap, SU5416, SU6668, ZD6474, PTK 757, IMC-1CII)
• No prior epidermal growth factor receptor-targeting therapy (e.g., gefitinib or cetuximab)
• More than 10 days since prior full-dose oral or parenteral anticoagulants or thrombolytic agents*
• No concurrent full-dose oral or parenteral anticoagulants or thrombolytic agents*
• No concurrent chronic daily aspirin (dose > 325 mg/day)
• No concurrent nonsteroidal anti-inflammatory medications known to inhibit platelet function (e.g., cyclo-oxygenase-1 inhibitors)
• No other concurrent investigational or commercial anticancer agents or therapies
• No concurrent combination antiretroviral therapy for HIV-positive patients NOTE: *Except for maintaining patency of preexisting, permanent indwelling IV catheters