MK2206 in Treating Patients With Advanced Refractory Biliary Cancer That Cannot Be Removed by Surgery
Condition: 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
MeSH terms: Carcinoma; Carcinoma, Hepatocellular; Gallbladder Neoplasms; Bile Duct Neoplasms; Liver Neoplasms; Recurrence
Intervention: Akt Inhibitor MK2206; Diagnostic Laboratory Biomarker Analysis; Pharmacological Study
Intervention description: Given PO; Correlative studies; Correlative studies
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 8.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial is studying how well MD2206 works in treating patients with advanced
      refractory biliary cancer that cannot be removed by surgery.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically confirmed biliary tract carcinoma that is surgically
             unresectable

               -  Cytological confirmation is not allowed on this study, as tissue is needed for
                  correlative science analysis

               -  Either fresh-frozen tissue (FFT) or paraffin-embedded tissue blocks (PETB) will
                  be required from patients before enrolling on this study

               -  No biopsies will be required unless there is insufficient tissue or if the PETB
                  available is more than 12 months old

          -  Patients must have measurable disease, defined as at least one lesion that can be
             accurately measured in at least one dimension (longest diameter to be recorded) as ≥
             10 mm with spiral CT scan (CT scan slice thickness no greater than 5 mm)

               -  Malignant lymph nodes will be considered measurable if they are ≥ 15 mm in short
                  axis

          -  Patients must have received one prior therapy for metastatic disease

               -  No prior Akt inhibitors allowed

          -  Patients with known brain metastases should be excluded from this clinical trial

          -  Life expectancy greater than 12 weeks

          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) =<2 (Karnofsky >=
             60%)

          -  Leukocytes >= 3,000/mcL

          -  Absolute neutrophil count (ANC) >= 1,500/mcL

          -  Platelet count >= 100,000/mcL

          -  Total bilirubin =< 1.5 x institutional upper limit of normal (IULN)

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
             [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT] =<
             2.5 x IULN

          -  Creatinine within normal institutional limits OR creatinine clearance >= 60
             mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
             (measured or calculated using the Cockroft-Gualt formula)

          -  Women of childbearing potential and men must use two forms of contraception (hormonal
             or barrier method of birth control; abstinence) prior to study entry and for the
             duration of study participation

          -  Not pregnant or nursing

          -  Able to swallow oral tablets

          -  No history of allergic reactions attributed to compounds of similar chemical or
             biologic composition to Akt Inhibitor MK2206 (MK2206) or other agents used in the
             study

          -  Patients with diabetes or in risk for hyperglycemia should not be excluded from trials
             with MK2206, but the hyperglycemia should be well controlled on oral agents before the
             patient enters the trial

          -  Cardiovascular: baseline QTcF > 450 msec (male) or QTcF > 470 msec (female) will
             exclude patients from entry on study

          -  Patients with clinically significant bundle branch block or pre-existing clinically
             significant bradycardia will be excluded from the study

          -  No uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection; symptomatic congestive heart failure; unstable angina pectoris; cardiac
             arrhythmia; or psychiatric illness/social situations that would limit compliance with
             study requirements

          -  No concurrent grapefruit or grapefruit juice

          -  For patients having prior cryotherapy, radiofrequency ablation, ethanol injection,
             transarterial chemoembolization (TACE), or photodynamic therapy, the following
             criteria must be met:

               -  6 weeks has elapsed since that therapy

               -  Indicator lesion(s) is/are outside the area of prior treatment or, if the only
                  indicator lesion is inside the prior treatment area, there must be clear evidence
                  of disease progression associated with that lesion

               -  Edges of the indicator lesion are clearly distinct on CT scanning

               -  Prior radiation therapy with or without the use of a fluoropyrimidine as a
                  radiosensitizer in the adjuvant setting will be allowed on study if > 12 weeks
                  have elapsed since therapy

               -  Prior palliative radiation therapy will allowed as long as > 4 weeks have elapsed
                  since therapy

          -  No patients who have had chemotherapy within 4 weeks (6 weeks for nitrosoureas or
             mitomycin C) prior to entering the study or those who have not recovered from adverse
             events due to agents administered more than 4 weeks earlier

          -  Patients may not be receiving any other investigational agents

          -  Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral
             therapy are ineligible

          -  Patients receiving any medications or substances that are inhibitors or inducers of
             CYP 450 3A4 are ineligible