This phase II trial studies how well erlotinib hydrochloride and bevacizumab work in treating patients with stage IV breast cancer. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. Giving erlotinib hydrochloride and bevacizumab may be an effective treatment for breast cancer.
PRIMARY OBJECTIVES: I. To determine the efficacy of bevacizumab in combination with OSI-774 (erlotinib hydrochloride) in patients with previously treated metastatic breast cancer, as measured by objective response rate. SECONDARY OBJECTIVES: I. To determine the toxicity of bevacizumab in combination with OSI-774 in patients with previously treated metastatic breast cancer. II. To evaluate the efficacy of bevacizumab in combination with OSI-774 in patients with previously treated metastatic breast cancer, as measured by time to disease progression, duration of response and the proportion of patients with stabilization of disease \>= 6 months. III. To determine the molecular profile of the patient's primary breast tumor, and to explore the relationship between these molecular characteristics and the response to treatment. IV. To explore changes in biological markers in pre- and post-treatment tumor tissue in a subset of patients with accessible sites of disease. V. To explore a pre- and post-treatment analysis of circulating endothelial cells and the relationship of this analysis to serum markers of angiogenesis as well as response to treatment. VI. To obtain serial measurements of circulating epithelial cells and explore the relationship of these cells with circulating endothelial cells, markers of angiogenesis, and epidermal growth factor receptor (EGFR) expression. OUTLINE: Patients receive erlotinib hydrochloride orally (PO) once daily (QD) on days 1-21 and bevacizumab intravenously (IV) over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up periodically.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
UCSF Medical Center-Mount Zion
San Francisco, California, United States
Memorial Sloan-Kettering Cancer Center
New York, New York, United States
Level of EGFR Expression
Estimated at the end of the trial Immunoreactivity will be evaluated qualitatively with regard to intensity as follows: Measured on a scale, ranging from 0-3+ 0=negative (no immunoreactivity) 1+ - 3+ = positive: * faint immunoreactivity (weak staining) * intense immunoreactivity (strong staining) Immunohistochemical studies will be performed on the tumor specimen to correlate the anti-tumor efficacy of OSI-774 and bevacizumab with pre-treatment molecular characteristics.
Time frame: Up to 12 years
Response Rate, Defined as Complete Response (CR) + Partial Response (PR), Using the Response Evaluation Criteria in Solid Tumors
Estimated at the end of the trial. Complete Response (CR):Disappearance of all target lesions Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD 55 Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started
Time frame: Up to 12 years
Duration of Response
The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started).Evaluation of Target Lesions Complete Response (CR):Disappearance of all target lesions Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD
Time frame: From the time measurement criteria are met for CR and PR until the first date that recurrent or progressive disease is objectively documented, assessed up to 12 years
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Masking
NONE
Enrollment
38
Time to Progression
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Time frame: From the start of treatment until the first date that recurrent or progressive disease is objectively documented, assessed up to 12 years
Number of Patients Evaluated for Toxicity
graded according to the National Cancer Institute Common Toxicity Criteria version 4.0
Time frame: up to 12 years
Participants With Duration of Stable Disease Greater Than or Equal to 6 Months
Duration of stable disease greater than or equal to 6 months
Time frame: From the start of treatment until the first date that recurrent or progressive disease is objectively documented, assessed up to 12 years