MK2206 in Treating Patients With Stage I, Stage II, or Stage III Breast Cancer
|Estrogen Receptor Negative Estrogen Receptor Positive HER2/Neu Negative HER2/Neu Positive Progesterone Receptor Negative Progesterone Receptor Positive Stage IA Breast Cancer Stage IB Breast Cancer Stage IIA Breast Cancer Stage IIB Breast Cancer Stage IIIA Breast Cancer Stage IIIB Breast Cancer Stage IIIC Breast Cancer Triple-Negative Breast Carcinoma||Drug: Akt Inhibitor MK2206 Procedure: Therapeutic Conventional Surgery Other: Pharmacological Study Other: Laboratory Biomarker Analysis||Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Pre-surgical Evaluation of MK-2206 in Patients With Operable Invasive Breast Cancer|
- Change in phospho-Akt (Ser473) levels [ Time Frame: Baseline to day 0 ]A Wilcoxon signed-rank matched-pairs test will be used to compare expression levels in paired pre- and post-MK-2206 tissue.
- Change in PI3K/AKT pathway expression [ Time Frame: Baseline to day 0 ]The Spearman rank correlation coefficient will be used to analyze any relationship between the expression levels of different biomarkers. The Wilcoxon signed-rank (matched-pairs) test will be used to compare expression levels between matched pre-and post-treatment samples. All p-values will be two-sided with statistical significance evaluated at the 0.05 alpha level. Ninety-five percent confidence intervals will be calculated to assess the precision of the obtained estimates.
- Change in KI-67 expression [ Time Frame: Baseline to day 0 ]The Spearman rank correlation coefficient will be used to analyze any relationship between the expression levels of different biomarkers. The Wilcoxon signed-rank (matched-pairs) test will be used to compare expression levels between matched pre-and post-treatment samples. All p-values will be two-sided with statistical significance evaluated at the 0.05 alpha level. Ninety-five percent confidence intervals will be calculated to assess the precision of the obtained estimates.
|Study Start Date:||April 2011|
|Study Completion Date:||May 2014|
|Primary Completion Date:||July 2013 (Final data collection date for primary outcome measure)|
Experimental: Treatment (Akt inhibitor MK2206)
Patients receive Akt inhibitor MK2206 PO on days -9 and -2, and undergo segmental resection or total mastectomy on day 0.
Drug: Akt Inhibitor MK2206
Other Name: MK2206Procedure: Therapeutic Conventional Surgery
Undergo surgeryOther: Pharmacological Study
Other Name: pharmacological studiesOther: Laboratory Biomarker Analysis
I. To assess for a decrease in phosphorylated (phospho)-protein kinase B (Akt) (Ser^473) levels in tissue after a pre-surgical trial of weekly MK2206 (Akt inhibitor MK2206) (2 doses) in patients with operable invasive breast cancer.
I. To evaluate the effects of MK2206 on the immunohistochemical expression of other phosphatidylinositide 3-kinase (PI3K)/AKT pathway biomarkers on pre-and post-MK2206 tumor tissue, such as phospho-S6 kinase.
II. To assess modulation of PI3K/AKT signaling following MK2206 use with reverse-phase protein microarray analysis.
III. To explore whether phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) mutations demonstrate different modulation of PI3K/Akt-pathway signaling as compared to tumors with loss of phosphatase and tensin homolog (PTEN).
IV. To 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. To 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. To determine safety and tolerability of MK2206 in patients with early-stage breast cancer.
VII. To 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.
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 study treatment, patients are followed up for 4 weeks.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01319539
|United States, New York|
|Albert Einstein College of Medicine|
|Bronx, New York, United States, 10461|
|Montefiore Medical Center - Moses Campus|
|Bronx, New York, United States, 10467-2490|
|Columbia University Medical Center|
|New York, New York, United States, 10032|
|Principal Investigator:||Kevin Kalinsky||Montefiore Medical Center - Moses Campus|