MK2206 in Treating Patients With Advanced Refractory Biliary Cancer That Cannot Be Removed by Surgery
|ClinicalTrials.gov Identifier: NCT01425879|
Recruitment Status : Completed
First Posted : August 30, 2011
Results First Posted : April 15, 2016
Last Update Posted : June 17, 2016
|Condition or disease||Intervention/treatment||Phase|
|Advanced Adult Hepatocellular Carcinoma Localized Non-Resectable Adult Liver Carcinoma Recurrent Adult Liver Carcinoma Recurrent Gallbladder Carcinoma Stage IV Distal Bile Duct Cancer Stage IV Gallbladder Cancer Unresectable Extrahepatic Bile Duct Carcinoma Unresectable Gallbladder Carcinoma||Drug: Akt Inhibitor MK2206 Other: Diagnostic Laboratory Biomarker Analysis Other: Pharmacological Study||Phase 2|
I. To evaluate the objective response rate (complete and partial response), as defined by the Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria, in patients with advanced refractory biliary cancers (BC) receiving Akt inhibitor MK2206 (MK2206).
I. To determine the frequency and severity of adverse events and tolerability of the regimen in patients with advanced refractory BC receiving MK2206.
II. To determine the overall and progression-free survival of patients with advanced refractory BC receiving MK2206.
III. To determine the presence of genetic mutations of PI3-kinase/ Akt pathway signaling-pathway genes relevant to BC and how these correlate with objective response to treatment with MK2206.
IV. To determine the pharmacokinetic and pharmacogenetic profile as a way of assessing inter-individual variability as well as how these relate to clinical outcomes.
V. To determine genetic variants and mutations in genes encoding drug-metabolizing enzymes and transporters, and genes involved in tumor biology, and how these may be related to response to treatment.
OUTLINE: This is a multicenter study.
Patients receive Akt inhibitor MK2206 orally (PO) on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Blood samples are collected at baseline and periodically during study for pharmacokinetic, pharmacogenetic, and other correlative studies. Previously collected tumor tissue is also analyzed.
After completion of study therapy, patients are followed up for 4 weeks.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||8 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Multi-Institutional Phase II Study of the Akt Inhibitor MK-2206 in Refractory Biliary Cancers|
|Study Start Date :||April 2011|
|Primary Completion Date :||May 2013|
|Study Completion Date :||May 2014|
Experimental: Treatment (Akt inhibitor MK2206)
Patients receive Akt inhibitor MK2206 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: Diagnostic Laboratory Biomarker Analysis
Correlative studiesOther: Pharmacological Study
- Overall Response Rate (Complete and Partial Response) as Defined by RECIST 1.1 [ Time Frame: Up to 4 weeks after completion of study treatment, for total treatment time of up to 1 year ]Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) 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; Overall Response (OR) = CR + PR.
- Frequency of Adverse Events Related to MK-2206 [ Time Frame: Up to 4 weeks after completion of study treatment, for total treatment time of up to 1 year ]Severity of adverse events is graded according to the NCI CTCAE 4.0.
- Overall Survival [ Time Frame: From study initiation to time of death, assessed up to 4 weeks after completion of study treatment ]Analyzed using Kaplan-Meier method.
- Progression-free Survival [ Time Frame: From start of treatment to time of documented progression or death whichever occurs first, assessed up to 4 weeks after completion of study treatment ]Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), 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
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01425879
|United States, California|
|USC / Norris Comprehensive Cancer Center|
|Los Angeles, California, United States, 90033|
|United States, District of Columbia|
|MedStar Georgetown University Hospital|
|Washington, District of Columbia, United States, 20007|
|United States, Georgia|
|Emory University/Winship Cancer Institute|
|Atlanta, Georgia, United States, 30322|
|United States, North Carolina|
|University of North Carolina at Chapel Hill|
|Chapel Hill, North Carolina, United States, 27599|
|United States, Ohio|
|Seidman Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center|
|Cleveland, Ohio, United States, 44106|
|Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center|
|Cleveland, Ohio, United States, 44195|
|Ohio State University Comprehensive Cancer Center|
|Columbus, Ohio, United States, 43210|
|United States, Texas|
|M D Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Tanios Bekaii-Saab||Ohio State University Comprehensive Cancer Center|