Dasatinib in Treating Patients With Advanced Liver Cancer That Cannot Be Removed by Surgery
Condition: Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Recurrent Adult Primary Liver Cancer
MeSH terms: Carcinoma; Carcinoma, Hepatocellular; Liver Neoplasms
Intervention: dasatinib
Intervention description: Given orally
Intervention MeSH terms: Dasatinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 25.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial is studying how well dasatinib works in treating patients with advanced
      liver cancer that cannot be removed by surgery. Dasatinib may stop the growth of tumor cells
      by blocking some of the enzymes needed for cell growth.
    

Eligibility criteria:

        Criteria:

          -  WBC >= 3,000/mm^3

          -  LVEF normal

          -  Histologically or cytologically confirmed hepatocellular carcinoma; Advanced disease,
             unresectable disease, no Childs C criteria

          -  Measurable disease, defined as >= 1 unidimensionally measurable lesion >= 20 mm by
             conventional techniques or >= 10 mm by spiral CT scan

          -  Not a candidate for percutaneous ethanol injection or radiofrequency ablation (RFA)

          -  Prior transarterial chemoembolization, ethanol, and RFA allowed if new lesions are
             present in the liver and there are no other sites of disease

          -  No pleural effusion or ascites requiring paracentesis within the past 4 weeks

          -  No known brain metastases

          -  ECOG performance status (PS) 0-1 OR Karnofsky PS 70-100%

          -  Life expectancy > 3 months

          -  Absolute neutrophil count >= 1,500/mm^3

          -  Platelet count >= 75,000/mm^3

          -  Bilirubin =< 2 times upper limit of normal (ULN)

          -  AST and ALT =<2.5 times ULN (5 times ULN if liver involvement by tumor)

          -  Creatinine =< 2 times ULN

          -  PT =< 1.5 times ULN (no anticoagulation)

          -  Albumin >= 2.5 mg/dL

          -  No history of allergic reactions attributed to compounds of similar chemical or
             biological composition to dasatinib

          -  No evidence of encephalopathy

          -  No condition that would preclude ability to swallow and retain dasatinib tablets,
             including any of the following:

               -  Gastrointestinal tract disease resulting in an inability to take oral medication;

               -  Requirement for IV alimentation;

               -  Prior surgical procedures affecting absorption:

               -  Active peptic ulcer disease

          -  No clinically significant ECG abnormalities

          -  No clinically significant cardiovascular disease, including any of the following:

               -  Myocardial infarction or ventricular tachyarrhythmia within the past 6 months;

               -  Prolonged QTc >= 480 msec (Fridericia correction);

               -  Major conduction abnormality (unless cardiac pacemaker is present)

          -  No other uncontrolled illness, including, but not limited to, any of the following:

               -  Ongoing or active infection;

               -  History of significant bleeding disorder, including congenital (von Willebrand's
                  disease) or acquired disorders (antifactor VIII antibodies);

               -  Psychiatric illness or social situation that would preclude study compliance

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception

          -  Recovered from all prior therapy

          -  One prior systemic chemotherapy regimen allowed

          -  Prior cryosurgery allowed

          -  More than 4 weeks since prior transarterial chemoembolization

          -  More than 4 weeks since prior radiotherapy

          -  Prior or concurrent localized palliative radiotherapy (i.e., bony metastasis) allowed
             provided it was administered for =< 3 days

          -  At least 7 days since prior and no concurrent antithrombotic and/or antiplatelet
             agents (e.g., warfarin, heparin, low molecular weight heparin, acetylsalicylic acid,
             and/or ibuprofen)

          -  At least 7 days since prior and no concurrent agents with proarrhythmic potential

          -  At least 7 days since prior and no concurrent medications or substances that are
             potent inhibitors or inducers of CYP3A4

          -  No concurrent combination antiretroviral therapy for HIV-positive patients

          -  No concurrent embolization or chemoembolization

          -  No concurrent systemic antacids (H2 receptor antagonists or proton pump inhibitors)

          -  Locally active antacids allowed provided they are held for 2 hours before and 2 hours
             after dasatinib dose

          -  No other concurrent investigational agents

          -  No other concurrent anticancer agents or therapies