Sorafenib and Fulvestrant in Treating Patients With Locally Advanced or Metastatic Breast Cancer That Did Not Respond to Aromatase Inhibitor Therapy
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: fulvestrant; sorafenib tosylate
Intervention description: Loading dose for cycle 1: 500 mg intramuscular(IM) on Day 1;250 mg IM on Day 15 Upon completion of the loading dose, a fixed dose of fulvestrant 250 mg IM will be administered on day 1 of the next 28 day cycle and every consecutive cycle until tumor progression or until unacceptable toxicity occurs requiring discontinuation of study therapy; Subjects will take sorafenib 800 mg/day administered as 400 mg bid (twice daily) each morning and evening approximately 12 hours apart. Treatment will begin on Day 1 of the study and continue daily until tumor progression or until an unacceptable toxicity occurs which would require delay, modification or discontinuation of study therapy
Intervention MeSH terms: Sorafenib; Fulvestrant
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 12.0
Sex: All
Minimum age: 18 Years
Maximum age: 120 Years
Healthy volunteers: No
Keywords: male breast cancer; stage IIIA breast cancer; stage IIIB breast cancer; stage IIIC breast cancer; stage IV breast cancer; recurrent breast cancer

Summary:

      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.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Diagnosis of incurable breast cancer

               -  Locally advanced or metastatic disease

          -  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

                    -  Bone-only metastases that can be imaged with bone scan AND magnetic
                       resonance imaging (MRI) or bone scan AND plain x-ray is considered
                       measurable disease

                    -  Tumor lesions that are situated in a previously irradiated area are
                       considered measurable only if they are progressing at the time of study
                       entry

               -  Evaluable disease includes unresectable skin/chest wall metastases that can be
                  photographed and whose size can be measured with a ruler

                    -  Bone-only metastases that can only be imaged using bone scan or malignant
                       pleural effusion(s) only are not considered evaluable disease

          -  Previously treated with a third-generation aromatase inhibitor (e.g., letrozole,
             anastrazole, or exemestane) AND meets one of the following criteria:

               -  Progressed during palliative aromatase inhibitor therapy

               -  Recurred during adjuvant aromatase inhibitor therapy

               -  Recurred within 12 months of completing adjuvant aromatase inhibitor therapy

          -  Human Epidermal growth factor Receptor 2(HER2/neu)-negative tumor

               -  No Human Epidermal growth factor Receptor 2(HER2/neu) overexpression (i.e., tumor
                  staining 3+ by immunohistochemistry [IHC] or gene amplified by Fluorescence In
                  Situ Hybridization [FISH])

          -  Hormone receptor status:

               -  Estrogen receptor and/or progesterone receptor positive, defined as ≥ 10% of
                  malignant cells with positive nuclear staining

        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:

               -  New York Heart Association(NYHA) class III-IV congestive heart failure

               -  Unstable angina (anginal symptoms at rest) or new-onset angina (within the past 3
                  months)

               -  Myocardial infarction within the past 6 months

               -  Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy

          -  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:

          -  See Disease Characteristics

          -  No prior chemotherapy for metastatic or unresectable locally advanced breast cancer

          -  No prior sorafenib tosylate or other Vascular endothelial growth
             factor(VEGF)-targeting therapies

          -  More than 2 weeks since prior major surgery or open biopsy

          -  No concurrent anticoagulation with warfarin or heparin

          -  No concurrent Hypericum perforatum (St. John wort) or rifampin

          -  No other concurrent anticancer agents, including chemotherapy or biological therapy

          -  No other concurrent investigational drugs

          -  Concurrent bisphosphonates allowed