A Phase II Study of Akt Inhibitor MK2206 in the Treatment of Recurrent Platinum-Resistant Ovarian, Fallopian Tube, or Peritoneal Cancer
|ClinicalTrials.gov Identifier: NCT01283035|
Recruitment Status : Completed
First Posted : January 25, 2011
Results First Posted : June 24, 2016
Last Update Posted : June 24, 2016
|Condition or disease||Intervention/treatment||Phase|
|Ovarian Sarcoma Recurrent Fallopian Tube Carcinoma Recurrent Ovarian Carcinoma Recurrent Primary Peritoneal Carcinoma||Drug: Akt Inhibitor MK2206 Other: Laboratory Biomarker Analysis||Phase 2|
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.
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.
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 (Clinical Trial)|
|Actual Enrollment :||6 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Study of MK-2206 in the Treatment of Recurrent High-Grade Serous Platinum-Resistant Ovarian, Fallopian Tube, or Primary Peritoneal Cancer|
|Study Start Date :||April 2011|
|Actual Primary Completion Date :||December 2014|
|Actual Study Completion Date :||December 2014|
Experimental: Treatment (Akt inhibitor MK2206)
Akt inhibitor MK2206 will be taken PO once a week for four weeks (one cycle). Treatment will continue for as long as a subject is benefiting from the study drug.
Drug: Akt Inhibitor MK2206
Other Name: MK2206Other: Laboratory Biomarker Analysis
- 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 [ Time Frame: Up to 3 years ]
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
- Association Between Select Biomarkers and Response to Akt Inhibitor MK2206 (as Assessed by Objective Tumor Response, Progression-free Survival, and Overall Survival) [ Time Frame: Up to 3 years ]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.
- 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 [ Time Frame: Up to 3 years ]Distributions will be estimated using Kaplan-Meier analysis.
- Duration of Progression-free Following Initiation of Therapy With Akt Inhibitor MK2206 in the Cohort of Patients Enrolled on This Study [ Time Frame: Up to 3 years ]Distributions will be estimated using Kaplan-Meier analysis.
- 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 ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01283035
|United States, Massachusetts|
|Massachusetts General Hospital Cancer Center|
|Boston, Massachusetts, United States, 02114|
|Dana-Farber Cancer Institute|
|Boston, Massachusetts, United States, 02115|
|Beth Israel Deaconess Medical Center|
|Boston, Massachusetts, United States, 02215|
|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:||Joyce Liu||Dana-Farber Cancer Institute|