S1222 Trial (Everolimus, Anastrozole and Fulvestrant) in Post-Menopausal Stage IV Breast Cancer

Exclusion Criteria

• •Patients who have taken luteinizing hormone-releasing hormone (LHRH) analogue as adjuvant therapy are eligible provided they have a) discontinued such therapy at least 12 months prior to registration AND b) have not resumed their menstrual periods.
• •Patients must not have had prior exposure to fulvestrant or mTOR inhibitors (e.g., rapamycin, everolimus, temsirolimus, deforolimus). Concurrent bisphosphonate therapy is allowed. Patients must not have prior treatment with any investigational drug within 28 days prior to registration and must not be planning to receive any other investigational drug for the duration of the study.
• •Patients must have an International Normalized Ratio (INR) ≤ 1.6 within 28 days prior to registration.
• •Patients must have adequate bone marrow function, as defined by Absolute Neutrophil Count (ANC) of ≥ 1,500/mL, hemoglobin ≥ 9 g/dL and a peripheral platelet count ≥ 100,000/ mL, all within 28 days prior to registration.
• •Patients must have adequate hepatic function obtained within 28 days prior to registration and documented by all of the following:
• •* Bilirubin ≤ 1.5 mg/dL (or ≤ 3.0 mg/dL if due to Gilbert's Syndrome)
• •* alanine aminotransferase (ALT) (SGPT) and aspartate aminotransferase (AST) (SGOT) ≤ 2.5 x Institutional Upper Limit of Normal (IULN), or ≤ 5 x IULN if hepatic metastases are present.
• •Patients must have adequate renal function with serum creatinine level ≤ IULN within 28 days prior to registration.
• •Patients must have a fasting cholesterol ≤ 300 mg/dL and triglycerides ≤ 2.5 x IULN obtained within 28 days prior to registration. Patients may be on lipid lowering agents to reach these values.
• •Patients must have a complete history and physical examination within 28 days prior to registration.
• •Patients must have a performance status of 0 - 2 by Zubrod criteria.
• •Patients must not have any Grade III/IV cardiac disease as defined by the New York Heart Association Criteria (i.e., patients with cardiac disease resulting in marked limitation of physical activity or resulting in inability to carry on any physical activity without discomfort), unstable angina pectoris, myocardial infarction within 6 months, or serious uncontrolled cardiac arrhythmia.
• •Patients must not have uncontrolled diabetes (defined as an Hg A1C \>7% within 28 days prior to registration).
• •Patients must not have an organ allograft or other history of immune compromise. Patients must not be receiving chronic, systemic treatment with corticosteroids or other immunosuppressive agent. Topical or inhaled corticosteroids are allowed.
• •Patients must be able to take oral medications. Patient may not have any impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of everolimus (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection).
• •Patients must not have received immunization with an attenuated live vaccine (e.g. intranasal influenza, MMR, oral polio, varicella, zoster, yellow fever and BCG vaccines) within seven days prior to registration nor have plans to receive such vaccination while on protocol treatment.
• •Patients must not have taken within 14 days prior to registration, be taking, nor plan to take while on protocol treatment, strong CYP3A4 inhibitors, and/or CYP3A4 inducers.
• •No other prior malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer or other cancer for which the patient has been disease-free for 5 years.