MK2206 in Treating Patients With Stage I, Stage II, or Stage III Breast Cancer
|ClinicalTrials.gov Identifier: NCT01319539|
Recruitment Status : Terminated (terminated early, due to toxicity)
First Posted : March 21, 2011
Results First Posted : August 1, 2017
Last Update Posted : August 30, 2017
|Condition or disease||Intervention/treatment||Phase|
|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|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||12 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Pre-surgical Evaluation of MK-2206 in Patients With Operable Invasive Breast Cancer|
|Study Start Date :||April 2011|
|Actual Primary Completion Date :||July 2013|
|Actual Study Completion Date :||July 2013|
Experimental: Treatment (Akt inhibitor MK2206)
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.
Drug: Akt Inhibitor MK2206
Other Name: MK2206
Procedure: Therapeutic Conventional Surgery
Other: Pharmacological Study
Other Name: pharmacological studies
Other: Laboratory Biomarker Analysis
- Change in pAKT Levels [ Time Frame: Baseline, 2 weeks (Day 0 - surgery) ]This is designed to evaluate response to therapy - comparing changes within group (example: invasive pre-MK-2206-treated core versus post-MK-2206-treated surgical tissue).
- Change in pS6 Levels [ Time Frame: Baseline, 2 weeks (Day 0 - surgery) ]This is designed to evaluate response to therapy - comparing changes within group (example: invasive pre-MK-2206-treated core versus post-MK-2206-treated surgical tissue).
- Change in Ki-67 Expression [ Time Frame: Baseline, 2 weeks (Day 0 - surgery) ]This is designed to evaluate response to therapy - comparing changes within group (example: invasive pre-MK-2206-treated core versus post-MK-2206-treated surgical tissue).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01319539
|United States, New York|
|Columbia University Medical Center|
|New York, New York, United States, 10032|
|Albert Einstein College of Medicine|
|The Bronx, New York, United States, 10461|
|Montefiore Medical Center - Moses Campus|
|The Bronx, New York, United States, 10467-2490|
|Principal Investigator:||Kevin Kalinsky||Montefiore Medical Center - Moses Campus|