Dasatinib in Treating Patients With Advanced Liver Cancer That Cannot Be Removed by Surgery

This is an interventional treatment trial for Adult Primary Hepatocellular Carcinoma Read More

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