MK2206 and Paclitaxel in Treating Patients With Locally Advanced or Metastatic Solid Tumors or Metastatic Breast Cancer

PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD) of the combination of MK-2206 and weekly paclitaxel. (Dose-escalation phase) II. To determine the safety and anti-tumor activity of the combination in metastatic breast cancer. (Expansion phase) SECONDARY OBJECTIVES: I. To determine the pharmacokinetics of MK-2206 and weekly paclitaxel used in combination. II. To determine the safety of MK-2206 and weekly paclitaxel used in combination. III. To evaluate the toxicities and tolerability of the combination. IV. To document anti-tumor activity. V. To determine baseline molecular markers that may predict clinical activity. VI. To determine pharmacodynamic markers in blood and tumor tissue that may predict an increase in apoptosis (by cleaved caspase 3) and clinical activity. VII. To determine concordance of phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) and phosphatase and tensin homolog (PTEN) status between primary tumor and distant metastasis. VIII. To determine concordance of PIK3CA status of circulating tumor cells and distant metastasis. OUTLINE: This is a dose-escalation study of Akt inhibitor MK2206. Patients receive paclitaxel intravenously (IV) over 1 hour on days 1, 8, and 15 and Akt inhibitor MK2206 orally (PO) once daily (QD) on days 2, 9, and 16. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 3 weeks.