LC Drug Eluting Bead for Treatment of Liver Cancer Which Cannot be Surgically Removed (HCC)

• Adults patients (≥ 18 years of age) with a diagnosis of HCC that is not amenable to surgical resection or local ablative therapy
• Histological confirmed HCC or clinical/laboratory diagnosis of HCC or nodules larger than 2cm with typical vascular features or AFP > 200
• Patient must have one lesion < 8cm or up to five lesions with total diameter < 8cm
• Quantifiable disease limited to the liver; 40% of liver must be free of tumor burden

• Patient must have at least one tumor lesion that meets both of the following criteria:

  • Lesion can be accurately measured in at least one dimension according to RECIST criteria
  • Lesion has not been previously treated with surgery, radiation therapy, radiofrequency ablation, percutaneous ethanol or acetic acid injection, or cryoablation.
• ECOG performance status ≤ 2
• No prior systemic chemotherapy
• At least 4 weeks since prior TACE or interferon
• Not pregnant
• No significant baseline liver dysfunction. Child-Pugh class A and B 7-8 (in abscence of ascites)
• No significant renal impairment (creatinine clearance < 30mL/minute) or patients on dialysis
• No current infections requiring antibiotic therapy
• Not on anticoagulation or suffering from a known bleeding disorder
• No unstable coronary artery disease or recent MI

• The following laboratory parameters

  • Hemoglobin ≥ 8.5g/dL
  • Total bilirubin ≤ 3.0mg/dL
  • ALT and AST ≤ 5x upper limit of normal
  • Serum creatinine ≤ 1.5x upper limit of normal
  • INR ≤ 1.5 or a PT/PTT within normal limits
  • Platelet count ≥ 50,000/uL
• Ability to understand the protocol and to agree to and sign a written informed consent document

Exclusion Criteria:

• HCC with gross vascular invasion or extrahepatic disease
• Previous or concurrent cancer that is distinct in primary site or histology from HCC except cervical carcinoma in situ, treated basal-cell carcinoma of the skin, superficial bladder tumors (Ta, Tis & T1), and any cancer curatively treated > 3 years prior to entry is permitted
• Renal failure requiring dialysis
• Child-Pugh B9 or C hepatic impairment
• History of cardiac disease: NYHA class 2 congestive heart failure, active coronary artery disease, cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin, and uncontrolled hypertension. Myocardial infarction more than 6 months prior to study entry is permitted.
• Active clinically serious infections (> CTCAEv3 grade 2)
• Known history of HIV
• Known central nervous system tumors including metastatic brain disease
• History of organ allograft
• Substance abuse (current), psychological, or social conditions that may interfere with the patient's participation in the study or evaluation of the study results.
• Allergy to the investigational agents or any agent given in association with this trial.
• Pregnant or breast-feeding patients. Both men and women enrolled in this trial must use adequate barrier birth control measures during the course of the trial.
• Uncontrolled hypertension defined as systolic blood pressure > 150mmHg or diastolic blood pressure > 90mmHg
• Thrombolic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months
• Pulmonary hemorrhage/bleeding event > CTCAE Grade 2 within 4 weeks of first dose of study drug
• Any other hemorrhage/bleeding event > CTCAE Grade 3 within 4 weeks of first dose of study drug
• Serious non-healing wound, ulcer, or bone fracture

• Any contraindication for doxorubicin administration:

  • serum bilirubin > 3mg/dL
  • WBC < 3000 cells/mm3
  • neutrophil < 1500 cells/mm3
  • cardiac ejection fraction < 50 percent assessed by isotopic ventriculography, echocardiography or MRI
  • MUGA scan < 40% ejection fraction
• Any contraindication for hepatic embolization procedures

Excluded therapies and medications, previous and concomitant:

• Prior use of any systemic anti-cancer chemotherapy for HCC
• Prior use of any systemic investigational agents for HCC
• Major surgery within 6 weeks of start of study drug
• Radiotherapy during study or within 3 weeks prior to start of study drug
• Use of biological response modifiers such as granulocyte colony-stimulating factor (G-CSF)within 3 weeks prio to study entry
• Autologous bone marrow transplant or stem cell rescue within four months of study drug initiation
• Concomitant treatment with rifampin or St. John's wort