Akt Inhibitor MK2206 in Treating Patients With Recurrent or Advanced Endometrial Cancer
Endometrial Adenosquamous Carcinoma
Endometrial Clear Cell Adenocarcinoma
Endometrial Serous Adenocarcinoma
Recurrent Uterine Corpus Carcinoma
Drug: Akt Inhibitor MK2206
Other: Laboratory Biomarker Analysis
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II, 2-Stage, 2-Arm PIK3CA Mutation Stratified Trial of MK-2206 in Recurrent or Advanced Endometrial Cancer|
- Objective tumor response according to RECIST [ Time Frame: Up to 6 months ] [ Designated as safety issue: No ]
- Progression-free survival according to RECIST [ Time Frame: From start of treatment to time of objective disease progression, assessed up to 6 months ] [ Designated as safety issue: No ]
- Duration of overall survival [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]Estimated by using Kaplan-Meier analysis.
- Duration of progression-free survival [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]Estimated by using Kaplan-Meier analysis.
- Incidence of adverse events as assessed by NCI CTCAE version 4.0 [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]
- Association between select biomarkers and response to Akt inhibitor MK2206 such as progression-free survival and objective tumor response, assessed by immunohistochemistry (IHC) [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
|Study Start Date:||March 2011|
|Primary Completion Date:||July 2012 (Final data collection date for primary outcome measure)|
Experimental: Treatment (Akt inhibitor MK2206
Patients receive Akt inhibitor MK2206 PO once weekly. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: Akt Inhibitor MK2206
Other Name: MK2206Other: Laboratory Biomarker Analysis
I. To assess the activity of MK-2206 (Akt inhibitor MK2206) in patients with recurrent or persistent endometrial cancer classified by phosphoinositide-3-kinase catalytic alpha (PIK3CA) mutation. Activity will be ascertained by the proportion of patients who survive progression-free for at least 6 months after initiating therapy or who have objective tumor response.
II. To evaluate the efficacy of MK2206 in patients with serous tumors using a composite endpoint of complete and partial response by Response Evaluation Criteria In Solid Tumors (RECIST) and progression-free interval of 6 months or longer.
I. To determine the duration of progression-free survival and overall survival. II. To determine the nature and degree of toxicity of MK-2206 as assessed by version 4 of the National Cancer Institute (NCI) Common Terminology Criteria For Adverse Events (CTCAE) in these cohorts of patients.
III. To explore the associations between select biomarkers and response to MK-2206 such as progression-free survival, objective tumor response, and overall survival as well as patient characteristics such as histological cell type.
IV. To explore the development of feed-back loop activation (post-treatment biopsy biomarker analysis) and target inhibition using MK-2206 via analysis of pre-treatment and post-treatment biopsies in select patients enrolled in the trial.
V. To determine the duration of progression-free and overall survival, following initiation of therapy with MK-2206.
VI. To determine the toxicities of MK-2206, as assessed with the revised NCI CTCAE version 4.
VII. To explore the association between select biomarkers and response to MK-2206 such as progression-free survival, objective tumor response.
Patients receive Akt inhibitor MK2206 orally (PO) once weekly. 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 years.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01307631
|United States, Massachusetts|
|Beth Israel Deaconess Medical Center|
|Boston, Massachusetts, United States, 02215|
|Dana-Farber Cancer Institute|
|Boston, Massachusetts, United States, 02115|
|Massachusetts General Hospital Cancer Center|
|Boston, Massachusetts, United States, 02114|
|Massachusetts General Hospital|
|Charlestown, Massachusetts, United States, 02129|
|Newton, Massachusetts, United States, 02462|
|United States, New York|
|Memorial Sloan-Kettering Cancer Center|
|New York, New York, United States, 10065|
|United States, Texas|
|M D Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Panagiotis Konstantinopoulos||Dana-Farber Cancer Institute|