Akt Inhibitor MK2206 in Treating Patients With Advanced Breast Cancer
Male Breast Cancer
Recurrent Breast Cancer
Stage IIIB Breast Cancer
Stage IIIC Breast Cancer
Stage IV Breast Cancer
Drug: Akt inhibitor MK2206
Other: laboratory biomarker analysis
Other: pharmacological study
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Trial of AKT Inhibitor MK2206 in Patients With Advanced Breast Cancer Who Have Tumors With a PIK3CA Mutation, or an AKT Mutation, and/or PTEN Loss/PTEN Mutation|
- Response rate defined using RECIST version 1.1 [ Time Frame: Up to 3 weeks after completion of study treatment ] [ Designated as safety issue: No ]
- Progression-free survival [ Time Frame: From start of treatment to time of progression or death, whichever occurs first, assessed up to 3 weeks after completion of study treatment ] [ Designated as safety issue: No ]Kaplan-Meier estimates will be provided for each individual cohort. Cox proportional hazards models will be fit for the progression-free survival time with mutation status as an independent variable adjusting for potential baseline predictive biomarkers.
- Cell proliferation as measured by the change in percent Ki-67 positive cells [ Time Frame: Baseline to 2 weeks ] [ Designated as safety issue: No ]
- Apoptosis assessed by cleaved caspase 3 [ Time Frame: Up to 30 days after completion of study treatment ] [ Designated as safety issue: No ]
|Study Start Date:||March 2011|
|Primary Completion Date:||August 2014 (Final data collection date for primary outcome measure)|
Experimental: Treatment (Akt inhibitor MK2206)
Patients receive Akt Inhibitor MK-2206 PO on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: Akt inhibitor MK2206
Other Name: MK2206Other: laboratory biomarker analysis
Correlative studiesOther: pharmacological study
Other Name: pharmacological studies
I. To determine whether v-akt murine thymoma viral oncogene (Akt) inhibitor MK2206 achieves objective tumor responses (complete response [CR], partial response [PR]) in advanced breast cancer patients who have a phosphoinositide-3-kinase, catalytic, alpha polypeptide (PIK3CA) or Akt mutation and/or phosphatase and tensin homolog (PTEN) loss or mutation.
I. To determine the 6 month progression-free survival on MK2206. II. To determine baseline molecular markers that may predict clinical outcome. III. To determine pharmacodynamic markers in blood and tumor tissue that may predict a decrease in Ki-67 and clinical outcome.
IV. To determine safety and tolerability of MK2206 in previously treated patients with advanced breast cancer.
V. To determine if decrease in Ki-67 at 2 weeks correlates with anti-tumor effect (CR, PR, or stable disease [SD] > 6 months).
VI. To determine concordance of PIK3CA and PTEN status between primary tumor and distant metastasis.
VII. To determine concordance of PIK3CA status of circulating free deoxyribonucleic acid (DNA) and distant metastasis.
Patients receive Akt Inhibitor MK-2206 orally (PO) on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 3 weeks.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01277757
|United States, Massachusetts|
|Beth Israel Deaconess Medical Center|
|Boston, Massachusetts, United States, 02215|
|Dana-Farber Cancer Institute|
|Boston, Massachusetts, United States, 02115|
|United States, New York|
|Columbia University Medical Center|
|New York, New York, United States, 10032|
|United States, Tennessee|
|Vanderbilt-Ingram Cancer Center|
|Nashville, Tennessee, United States, 37232|
|United States, Texas|
|M D Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Funda Meric-Bernstam||M.D. Anderson Cancer Center|