This phase II trial is studying how well MD2206 works in treating patients with advanced refractory biliary cancer that cannot be removed by surgery.
PRIMARY OBJECTIVES: 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). SECONDARY OBJECTIVES: 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
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
8
Given PO
Correlative studies
Correlative studies
USC / Norris Comprehensive Cancer Center
Los Angeles, California, United States
MedStar Georgetown University Hospital
Washington D.C., District of Columbia, United States
Emory University/Winship Cancer Institute
Atlanta, Georgia, United States
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States
Seidman Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center
Cleveland, Ohio, United States
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Cleveland, Ohio, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States
M D Anderson Cancer Center
Houston, Texas, United States
Overall Response Rate (Complete and Partial Response) as Defined by RECIST 1.1
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.
Time frame: Up to 4 weeks after completion of study treatment, for total treatment time of up to 1 year
Frequency of Adverse Events Related to MK-2206
Severity of adverse events is graded according to the NCI CTCAE 4.0.
Time frame: Up to 4 weeks after completion of study treatment, for total treatment time of up to 1 year
Overall Survival
Analyzed using Kaplan-Meier method.
Time frame: From study initiation to time of death, assessed up to 4 weeks after completion of study treatment
Progression-free Survival
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
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
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