Phase Ib Dose Escalation and Biomarker Study of MK-2206 in Combination With Standard Doses of Weekly Paclitaxel in Patients With Locally Advanced or Metastatic Solid Tumors With an Expansion in Advanced Breast Cancer
I. To determine the 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)
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 PIK3CA and PTEN status between primary tumor and distant
VIII. To determine concordance of PIK3CA status of circulating tumor cells and distant
OUTLINE: This is a multicenter, 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.
Tumor tissue and blood samples are collected periodically for pharmacodynamic and
After completion of study treatment, patients are followed up for 3 weeks.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
MTD of the combination of MK-2206 and weekly paclitaxel determined by dose-limiting toxicities (Phase I)
Ana Maria Gonzalez-Angulo
M.D. Anderson Cancer Center
United States: Food and Drug Administration
|Dana-Farber Cancer Institute||Boston, Massachusetts 02115|
|M D Anderson Cancer Center||Houston, Texas 77030|