Study of Fulvestrant +/- Everolimus in Post-Menopausal, Hormone-Receptor + Metastatic Breast Ca Resistant to AI

Inclusion Criteria

• Signed informed consent.
• ≥18 years.
• ECOG Performance Status 0 or 1.
• Histologically or cytologically confirmed adenocarcinoma of the breast.
• Stage IV disease or inoperable locally advanced disease.
• ER and/or PR-positive disease. Tumors must be HER-2/neu negative or equivocal.
• Aromatase Inhibitor (AI) resistant, defined as:
• relapsed while receiving adjuvant therapy with an AI or,
• progressive disease while receiving an AI for metastatic disease
• Received one prior cycle of fulvestrant within 28 days of randomization are eligible.
• ≥2 prior doses of fulvestrant are not eligible
• Must be female and postmenopausal.
• May have received ≤1 prior systemic chemotherapy regimen for metastatic disease.
• Adequate organ function:
• Whole Blood Cells (WBC) ≥3.0 x 10⁹/L, Absolute neutrophil count (ANC) ≥1.5 x 10⁹/L and platelet count ≥100 x 10⁹/L
• hemoglobin ≥9 g/dL
• serum bilirubin ≤1.5 X ULN (Upper Limit of Normal)
• Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) ≤2.5 X ULN (≤5 x ULN in patients with liver metastases)
• serum creatinine ≤1.5 X ULN
• serum albumin ≥3 g/dL
• fasting serum cholesterol ≤300 mg/dL OR ≤7.75 mmol/L AND fasting triglycerides ≤2.5 x ULN.
• Prothrombin time (PT) with international normalized ratio (INR) ≤1.5
• May have measurable disease, non-measurable disease, or both.
• Basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix within the past five years treated with curative intent. History of prior malignancy are eligible if disease-free for >3 years.

Exclusion Criteria

• Major surgery or significant traumatic injury within 4 weeks of randomization or patients that may require major surgery during the course of the study.
• Investigational agents within 4 weeks of randomization.
• Anticancer treatment within 4 weeks of randomization, with the following exceptions:
• Bisphosphonates or Zometa for bone metastases
• a GnRH analog is permitted if the patient had progressive disease on a GnRH (Gonadotropin-Releasing Hormone) analog plus a SERM (Selective Estrogen Receptor Modulators) or an AI; the GnRH analog may continue but the SERM or AI must be discontinued.
• Prior treatment with an mTOR inhibitor.
• Receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent ≥ 5 mg prednisone or equivalent daily.
• Receive immunization with attenuated live vaccines within one week of randomization or during the study period.
• Current or a prior history of brain metastases or leptomeningeal disease. Must not have rapidly progressive, life-threatening metastases.
• Known hypersensitivity/history of allergic reactions attributed to compounds of similar chemical or biologic composition to everolimus or fulvestrant.
• Congenital or acquired immune deficiency at increased risk of infection.
• Impairment of gastrointestinal function/disease that may significantly alter the absorption of everolimus.
• Active, bleeding diathesis.
• History of any condition or uncontrolled intercurrent illness that in the opinion of the local investigator might interfere with or limit the patient's ability to comply with the protocol or pose additional or unacceptable risk to the patient.
• Severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
• Symptomatic congestive heart failure of New York Heart Association Class III or IV
• Unstable angina pectoris, myocardial infarction within 6 months of randomization, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease
• History of symptomatic pulmonary disease or non-malignant pulmonary disease requiring treatment.
• Uncontrolled diabetes as defined by fasting serum glucose >1.5 x ULN
• Active (acute or chronic) or uncontrolled severe infections
• Liver disease such as cirrhosis or severe hepatic impairment (Child-Pugh Class C). Note: Detailed assessment of Hepatitis B/C medical history and risk factors must be done at screening.