MK-2206+Endocrine Therapy in Patients With Hormone Receptor-Positive Breast Cancer

Exclusion Criteria

• •1. Chemotherapy, radiotherapy, or biological therapy within 3 weeks (6 weeks for nitrosoureas, mitomycin C or bevacizumab), or not recovered from the adverse events due to previous agents administered more than 4 weeks prior to Study Day 1. If residual toxicity from prior treatment,toxicity must be ≤ Grade 1
• •2. Must be at least 4 weeks post-major surgical procedure, and all surgical wounds must be fully healed
• •3. Currently participating or has participated in a study with an investigational compound or device within 30 days of Study Day 1
• •4. Known active CNS metastases and/or carcinomatous meningitis. However, patients with CNS metastases who have completed a course of therapy would be eligible for the study provided they are clinically stable for at least 1 month prior to entry as defined as: (1) no evidence of new or enlarging CNS metastasis (2)off steroids used to minimize surrounding brain edema
• •5. Primary central nervous system tumor
• •6. Known hypersensitivity to the components of study drug or its analogs
• •7. History or current evidence of clinically significant heart disease including:
• •* congestive heart failure, unstable angina pectoris,
• •* cardiac arrhythmia,
• •* history or current evidence of a myocardial infarction during the last 6 months,and/or a current ECG tracing that is abnormal in the opinion of the treating Investigator,
• •* baseline QTc prolongation \> 450 msec (Bazett's Formula). Medications included in Arizona CERT Lists 1 and 2 (Appendix D) must be excluded. The concomitant use of drugs that are associated with increased risk for QT prolongation should be avoided in patients with congenital long QT syndrome (Appendix D, Arizona CERT List 3). Similarly, the concomitant use of drugs that are weakly associated with QT prolongation should be generally avoided (Appendix D, Arizona CERT List 4). Arizona CERT List 3 and 4 drugs should be used at the discretion of the Investigator and restricted where applicable. Any therapy given with these drugs should be used with caution, and patients receiving these medications should be carefully monitored.
• •8. Evidence of clinically significant bradycardia (HR \<50), or a history of clinically significant bradyarrhythmias such as sick sinus syndrome, 2nd degree AV block (Mobitz Type 2), or patients taking beta blockers, non-dihydropyridine calcium channel blockers, or digoxin
• •9. Uncontrolled hypertension (i.e., 160/90 mHg SiBP). Patients who are controlled on antihypertensive medication will be allowed to enter the study
• •10. At significant risk for hypokalemia (e.g., patients on high dose diuretics, or with recurrent diarrhea)
• •11. Poorly controlled diabetes defined as HbA1C \> 8%
• •12. History or current evidence of any condition, therapy, or lab abnormality that might confound the study results, interfere with the patient's participation for the full study duration, or is not in the best interest of the patient to participate, in the opinion of the treating Investigator
• •13. Known psychiatric or substance abuse disorders that would interfere with cooperation with trial requirements
• •14. Patient is, at the time of signing informed consent, a regular user (including "recreational use") of any illicit drugs or had a recent history (within the last year) of drug or alcohol abuse
• •15. Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study
• •16. Human Immunodeficiency Virus (HIV)-positive
• •17. Known history of Hepatitis B or C or active Hepatitis A
• •18. Symptomatic ascites or pleural effusion. Patient who is clinically stable following treatment for these conditions is eligible
• •19. Receiving treatment with oral corticosteroids (note: inhaled corticosteroids are permitted)