LC Drug Eluting Bead for Treatment of Liver Cancer Which Cannot be Surgically Removed
Condition: Hepatocellular Carcinoma
MeSH terms: Carcinoma; Carcinoma, Hepatocellular
Intervention: LC Bead loaded with doxorubicin
Intervention description: LC Bead is a new product specifically designed for TACE. LC Bead microspheres will be loaded with between 50-100mg of doxorubicin for each of several TACE procedures. The bead will utilize embolic induced ischemia as well as local chemotherapy in an effort to downstage unresectable HCC to liver transplantation
Intervention MeSH terms: Doxorubicin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 2.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Advanced HCC represents a high unmet medical need with a poor prognosis and few therapeutic
      options. Patients who present with HCC beyond the currently accepted Milan criteria are not
      eligible to be listed for liver transplantation. The proposed study offers local regional
      therapy to a defined population of patients beyond Milan criteria as an attempt to downstage
      them to eligibility for liver transplant.
    

Eligibility criteria:

        -  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