Akt inhibitor MK2206 is a drug that may stop cancer cells from growing by blocking a protein called protein kinase B (AKT) inside the cell. AKT interacts with other proteins in the cell that are part of the P13K/AKT pathway, a pathway that is know to play a role in the growth of cancer cells. Mutations in P13K or in AKT, or changes in another protein called phosphatase and tensin homolog (PTEN) in this pathway can lead it to become more active than is normal. This study investigates how effective MK-2206 is in treating ovarian, fallopian tube, or primary peritoneal cancer where there are mutations in P13K or AKT or low levels of PTEN.
PRIMARY OBJECTIVES: I. To assess the activity of MK-2206 (Akt inhibitor MK2206) in patients with recurrent grade 2 or 3 platinum-resistant high-grade serous ovarian, fallopian tube, or peritoneal cancer, as measured by the frequency of patients experiencing an objective tumor response by Response Evaluation Criteria In Solid Tumors (RECIST) criteria or who survive progression-free for at least 6 months after initiation of therapy. SECONDARY OBJECTIVES: I. To assess the duration of progression-free and overall survival following initiation of therapy with MK-2206 in the cohort of patients enrolled on this study. II. To determine the toxicities of MK-2206, as assessed by the active version of the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0 III. To explore the association between select biomarkers and response to MK-2206 (as assessed by objective tumor response, progression-free survival, and overall survival) IV. To explore the development of feedback loop activation and target inhibition with MK-2206 via analysis of pre-treatment and post-treatment biopsies in select patients enrolled in the trial. OUTLINE: Akt inhibitor MK2206 will be taken orally (PO) once a week for four weeks (one cycle). Treatment will continue for as long as a subject is benefiting from the study drug. During each cycle subjects will have a physical exam, blood samples and an electrocardiogram (EKG) (first 2 cycles). Every 2 cycles a computed tomography (CT) scan or magnetic resonance imaging (MRI) of chest, stomach area, and pelvis will be performed. Optional tumor biopsies may be performed.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
6
Given PO
Correlative studies
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States
Newton-Wellesley Hospital
Newton, Massachusetts, United States
Memorial Sloan-Kettering Cancer Center
New York, New York, United States
M D Anderson Cancer Center
Houston, Texas, United States
Efficacy (as Measured by Objective Response Rate) of Akt Inhibitor MK2206 in Patients With Recurrent High-grade Platinum-resistant Serous Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
If 4 or more of the final set of 29 patients demonstrate a response, then the null hypothesis H0: =\< 5% can be rejected in favor of the alternative hypothesis H1: \>= 20% with an alpha of 0.05 and beta of 0.20 (i.e., 80% power). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progression, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression
Time frame: Up to 3 years
Association Between Select Biomarkers and Response to Akt Inhibitor MK2206 (as Assessed by Objective Tumor Response, Progression-free Survival, and Overall Survival)
The frequency of mutations in the PI3K/AKT and RAS pathways, copy number alterations, and PTEN loss and AKT expression as assessed by IHC will be tabulated. Associations between these markers with clinical outcome such as response rate and duration of PFS will be assessed.
Time frame: Up to 3 years
Development of Feedback Loop Activation and Target Inhibition With Akt Inhibitor MK2206 Via Analysis of Pre-treatment and Post-treatment Biopsies in Select Patients Enrolled in the Trial
Time frame: Up to 3 years
Duration of Overall Survival Following Initiation of Therapy With Akt Inhibitor MK2206 in the Cohort of Patients Enrolled on This Study
Distributions will be estimated using Kaplan-Meier analysis.
Time frame: Up to 3 years
Duration of Progression-free Following Initiation of Therapy With Akt Inhibitor MK2206 in the Cohort of Patients Enrolled on This Study
Distributions will be estimated using Kaplan-Meier analysis.
Time frame: Up to 3 years
Toxicities of Akt Inhibitor MK2206, as Assessed by the Active Version of the NCI Common Terminology Criteria for Adverse Events (CTCAE v4.0)
Time frame: Up to 3 years
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