A Phase II Open-Label Study of Sorafenib Plus Fulvestrant as Salvage Therapy for Hormone Receptor Positive Metastatic Breast Cancer Failing Prior Aromatase Inhibitor Treatment
A Phase II Open-Label Study of Sorafenib Plus Fulvestrant as Salvage Therapy for Hormone Receptor Positive Metastatic Breast Cancer Failing Prior Aromatase Inhibitor Treatment
RATIONALE: Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. 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. Giving sorafenib together with fulvestrant may kill more tumor cells.
PURPOSE: This phase II trial is studying how well giving sorafenib together with fulvestrant works in treating patients with locally advanced or metastatic breast cancer that did not respond to aromatase inhibitor therapy.
OBJECTIVES:
Primary
Secondary
OUTLINE: Patients receive oral sorafenib tosylate twice daily on days 1-28. Patients also receive fulvestrant intramuscularly on days 1 and 15 of course 1 and on day 1 of all subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed at 28-56 days.
DISEASE CHARACTERISTICS:
Diagnosis of incurable breast cancer
Measurable or evaluable disease
Measurable disease is defined as ≥ 1 uni-dimensionally measurable lesion ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral computed tomography(CT) scan
Evaluable disease includes unresectable skin/chest wall metastases that can be photographed and whose size can be measured with a ruler
Previously treated with a third-generation aromatase inhibitor (e.g., letrozole, anastrazole, or exemestane) AND meets one of the following criteria:
Human Epidermal growth factor Receptor 2(HER2/neu)-negative tumor
Hormone receptor status:
PATIENT CHARACTERISTICS:
Postmenopausal
Eastern Cooperative Group(ECOG) performance status 0-1
Life expectancy ≥ 16 weeks
Neutrophil count ≥ 1,500/mm^³
Platelet count ≥ 100,000/mm^³
Hemoglobin ≥ 9.0 g/dL
Creatinine < 2 mg/dL
Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
Alanine aminotransferase (ALT) and aspartate aminotransferase(AST) ≤ 2.5 times ULN (≤ 5 times ULN for patients with liver involvement)
International Normalized Ratio(INR) < 1.5 OR Prothrombin time/ partial thromboplastin time (PT/PTT) normal
Left ventricular ejection fraction(LVEF) normal by Multiple Gated Acquisition(MUGA) or ECHO
No known allergy to sorafenib tosylate or fulvestrant
No cardiac disease, including any of the following:
No uncontrolled hypertension, defined as systolic blood pressure > 150 mm Hg or diastolic blood pressure > 90 mm Hg despite optimal medical management
No thrombotic or embolic events, such as cerebrovascular accident (including transient ischemic attacks), within the past 6 months
No known HIV infection or chronic hepatitis B or C infection
No infection that requires IV antibiotics or produces a fever > 100°F within the past 72 hours
No pulmonary hemorrhage/bleeding event ≥ Common terminology criteria for adverse events(CTCAE) grade 2 within the past 4 weeks
No other hemorrhage/bleeding event ≥ CTCAE grade 3 within the past 4 weeks
No evidence or history of bleeding diathesis or coagulopathy
No significant traumatic injury within the past 2 weeks
No serious, nonhealing wound, ulcer, or bone fracture
No condition that impairs the patient's ability to swallow whole pills
No malabsorption problem
No second malignancy within the past 5 years, except adequately treated and cured basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
No underlying medical condition that, in the principal investigator's opinion, will make the administration of study drug hazardous or would obscure the interpretation of adverse events
PRIOR CONCURRENT THERAPY: