Pre-surgical Evaluation of MK-2206 in Patients With Operable Invasive Breast Cancer
I. Assess for a decrease in phospho-Akt (Ser^473) levels in tissue after a pre-surgical
trial of weekly protein Kinase B (Akt) inhibitor MK2206 (MK2206) (2 doses) in patients with
operable invasive breast cancer.
I. Evaluate the effects of MK2206 on the immunohistochemical expression of other PI3K/AKT
pathway biomarkers on pre-and post-MK2206 tumor tissue, such as phospho-S6 kinase.
II. Assess modulation of PI3K/AKT signaling following MK2206 use with reverse-phase protein
III. Explore whether PIK3CA mutations demonstrate different modulation of PI3K/Akt-pathway
signaling as compared to tumors with loss of phosphatase and tensin homolog(PTEN).
IV. Explore whether MK2206 alters PI3K/Akt pathway signaling differently in hormone
receptor-positive/human epidermal growth factor receptor (HER)2-negative tumors, as compared
to triple-negative or HER2-positive breast cancers.
V. Evaluate whether tumor proliferation, as measured by Ki-67 staining of breast tumor
cells, is reduced in patients taking MK2206 pre-surgically and correlate Ki-67 modulation
with changes in PI3K/AKT signaling.
VI. Determine safety and tolerability of MK2206 in patients with early-stage breast cancer.
VII. Collect fasting blood for evaluation of predictive markers of drug effect, such as
markers in the insulin growth-factor receptor pathway (i.e., fasting insulin, c-peptide,
insulin-like growth factor (IGF)-1, and IGF binding protein (BP)-1 and 3), as well as
modulation of phospho-markers in peripheral blood mononuclear cells.
OUTLINE: This is a multicenter study.
Patients receive Akt inhibitor MK2206 orally (PO) on days -9 and -2, and undergo segmental
resection or total mastectomy on day 0.
After completion of therapy, patients are followed up for 4 weeks.
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Change in phospho-Akt (Ser473) levels
A Wilcoxon signed-rank matched-pairs test will be used to compare expression levels in paired pre- and post-MK-2206 tissue.
Baseline and day 0
Montefiore Medical Center
United States: Food and Drug Administration
|Montefiore Medical Center||Bronx, New York 10467-2490|