RATIONALE: Erlotinib may stop the growth of tumor cells by blocking the enzymes needed for their growth. Monoclonal antibodies, such as bevacizumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or deliver cancer-killing substances to them. Combining erlotinib with bevacizumab may kill more tumor cells.

PURPOSE: This phase II trial is to see if combining erlotinib with bevacizumab works in treating women who have stage IV breast cancer.

Condition	Treatment or Intervention	Phase
stage IV breast cancer recurrent breast cancer Male Breast Cancer	Drug: bevacizumab  Drug: erlotinib  Procedure: anti-cytokine therapy  Procedure: antiangiogenesis therapy  Procedure: antibody therapy  Procedure: biological response modifier therapy  Procedure: enzyme inhibitor therapy  Procedure: growth factor antagonist therapy  Procedure: monoclonal antibody therapy  Procedure: protein tyrosine kinase inhibitor therapy	Phase II

Further Study Details: 

OBJECTIVES:

• Determine the efficacy of erlotinib and bevacizumab, in terms of objective response rate, in women with previously treated stage IV breast cancer.
• Determine the toxicity of this regimen in these patients.
• Determine the time to disease progression and duration of response of patients treated with this regimen.
• Determine the proportion of patients achieving stabilization of disease for at least 6 months after treatment with this regimen.
• Correlate the molecular profile of the primary breast tumor with response in patients treated with this regimen.
• Correlate an analysis of circulating endothelial cells with serum markers of angiogenesis and response in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive oral erlotinib once daily and bevacizumab IV over 30-90 minutes once every 3 weeks. Courses repeat in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 12-37 patients will be accrued for this study within 4-18.5 months.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

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
• 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

New York
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States

Study chairs or principal investigators

Maura Dickler, MD,  Study Chair,  Memorial Sloan-Kettering Cancer Center   

Study ID Numbers:  CDR0000269900; MSKCC-02119; NCI-5761; NCT00054132
Record last reviewed:  March 2005
Last Updated:  March 28, 2005
Record first received:  February 5, 2003
ClinicalTrials.gov Identifier:  NCT00054132
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08