Clinical trial NCT01319539
Conditions: 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
Sponsor: National Cancer Institute (NCI)
Start date: 2011-04-01; Completion date: 2013-07-01
Enrollment: 12 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This phase II trial is studies how well Akt inhibitor MK2206 works in treating patients with stage I-III breast cancer that can be removed by surgery. Akt inhibitor MK2206 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed description:
PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

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.

OUTLINE:

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.

Arms: arm 1: Patients receive Akt inhibitor MK2206 PO on days -9 and -2, and undergo segmental resection or total mastectomy (therapeutic conventional surgery) on day 0. Patient samples will be processed for pharmacological study and laboratory biomarker analysis.
Interventions: intervention 1: Akt Inhibitor MK2206 intervention 2: Therapeutic Conventional Surgery intervention 3: Pharmacological Study intervention 4: Laboratory Biomarker Analysis
Intervention descriptions: intervention 1: Given PO intervention 2: Undergo surgery intervention 3: Correlative studies intervention 4: Correlative studies

Protocol documents: