MK2206 in Treating Patients With Advanced Liver Cancer That Did Not Respond to Previous Therapy
Condition: Adult Hepatocellular Carcinoma; Advanced Adult Hepatocellular Carcinoma; Localized Non-Resectable Adult Liver Carcinoma; Recurrent Adult Liver Carcinoma
MeSH terms: Carcinoma; Carcinoma, Hepatocellular; Liver Neoplasms
Intervention: Akt Inhibitor MK2206; Laboratory Biomarker Analysis
Intervention description: Given PO; Correlative studies
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 15.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial is studying how well MK2206 works in treating patients with advanced
      liver cancer that did not respond to previous therapy. MK2206 may stop the growth of tumor
      cells by blocking some of the enzymes needed for cell growth.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Unresectable or metastatic HCC for which standard curative measures do not exist

               -  The diagnosis of hepatocellular carcinoma should be based on at least one of the
                  following:

                    -  The presence of one or more liver lesions, measuring >= 2 cm, with
                       characteristic arterial enhancement and venous washout in the setting of
                       liver cirrhosis and/or hepatitis B or C infection

                    -  The presence of liver lesion(s) with AFP >= 400

                    -  Tissue confirmation in the absence of either or both of the above

                    -  Tissue availability is desired and will be sought, but tissue availability
                       is not mandated for accrual to the study

          -  Patients must have measurable disease, defined as at least one lesion that can be
             accurately measured in at least one dimension, and that has not been the target of
             local or regional therapy including transarterial chemoembolization, intra-arterial
             chemotherapy, ethanol, or RFA ablation

          -  One prior line of systemic anti-angiogenic therapy is required; this type of therapy
             includes, but is not restricted to, sorafenib, bevacizumab, sunitinib, or brivanib
             given as single agents or in combination with other agents

          -  No clinically evident ascites (minimal, medically controlled ascites detectable on
             imaging studies only is allowed)

          -  No Child-Pugh C cirrhosis or Child-Pugh B cirrhosis with more than 7 points

          -  No fibrolamellar carcinoma or any mixed variants of HCC with dominant fibrolamellar
             histology

          -  Patients with known brain metastases should be excluded from this clinical trial

          -  ECOG 0-1

          -  Life expectancy of greater than 3 months

          -  Leukocytes >= 3,000/mcL

          -  Absolute neutrophil count > 1,000 mcL

          -  Platelets >= 70,000/mcL

          -  Total bilirubin =< 1.5 institutional upper limit of normal

          -  AST (SGOT)/ALT (SGPT) < 5 x institutional upper limit of normal

          -  Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min

          -  Serum albumin >= 2.8 g/dL

          -  Not pregnant or nursing

          -  Fertile patients 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

          -  Must agree to collection of correlative blood samples during the study

          -  No patients unable to swallow pills or diagnosed with a gastrointestinal disorder that
             is likely to interfere with the absorption of MK-2206 or with the patient's ability to
             take regular oral medication

          -  Patients with hyperglycemia should be well controlled on oral agents before the
             patient enters the trial

          -  Patients with HgbA1C levels >= 8% or fasting blood glucose >= 150 mg/dL are not
             eligible for this study

          -  Baseline QTcF > 450 msec (male) or QTcF> 470 msec (female) will exclude patients from
             entry on study

          -  Patients with hepatitis B infection, defined by a positive hepatitis B surface antigen
             test, should be on suppressive anti-viral therapy

               -  Only the following anti-viral therapies are allowed while a patient is on study:
                  tenofovir disoproxil fumarate and entecavir

               -  Patients with hypothyroidism must be on a stable dose of thyroid replacement and
                  be clinically euthyroid

          -  No esophageal or gastric variceal bleeding within the last 6 months

               -  Patients with prior history of variceal bleeding must have had an upper endoscopy
                  (EGD) with appropriate treatment of varices within 6 months prior to study entry

          -  No uncontrolled intercurrent illness including, but not limited to:

               -  Ongoing or active infection

               -  Symptomatic congestive heart failure

               -  Unstable angina pectoris

               -  Cardiac arrhythmia

               -  Psychiatric illness/social situations that would limit compliance with study
                  requirements

          -  None of the following:

               -  Uncontrolled hypertension (systolic BP > 150 or diastolic BP > 100 on two
                  occasions within two weeks of beginning therapy on this protocol)

               -  Myocardial infarction within 6 months

               -  NYHA class > II

               -  Clinically significant bradycardia related to underlying cardiac disease

               -  Clinically significant bundle branch block related to underlying cardiac disease

          -  No patients with second primary cancer (except adequately treated nonmelanoma skin
             cancer, curatively treated in-situ cancer of the cervix, or other solid tumors
             including lymphomas without bone marrow involvement curatively treated with no
             evidence of disease for ≥ 5 years)

               -  The exception to this criterion is prostate cancer treated definitively with
                  surgery and/or radiation with normal PSA and no clinical evidence of residual or
                  recurrent prostate cancer

          -  HIV-positive patients on combination antiretroviral therapy are ineligible

          -  No history of allergic reactions attributed to compounds of similar chemical
             orbiologic composition to MK-2206 or other agents used in the study

          -  No medications that cause QTc interval prolongation

          -  Any number of prior regional therapies with transarterial chemoembolization,
             intra-arterial chemotherapy, or ablative therapy is allowed

               -  No more than 1 prior line of systemic therapy for advanced and/or unresectable
                  disease

          -  No patients who have had anti-angiogenic therapy, chemotherapy, radiotherapy or
             regional therapy (such as transarterial chemoembolization, intra-arterial
             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

               -  Localized radiation for palliation (i.e., bony metastasis, etc.) given for < 3
                  days is allowed before therapy and is not subject to the 4-week waiting
                  requirement

               -  Local ablative therapy such as radiofrequency ablation or cryotherapy must have
                  been completed more than 2 weeks prior to study entry

          -  Patients may not be receiving any other investigational or non-investigational agents
             or therapies directed at treating their hepatocellular carcinoma

          -  Patients may not be receiving any other investigational agents for any condition

          -  Patients receiving any medications or substances that are inhibitors or inducers of
             CYP3A4 are ineligible