HepaSphere/Quadrasphere Microspheres for Delivery of Doxorubicin for the Treatment of Hepatocellular Cancer (HiQuality)

• Objective Response Rates (ORR) [ Time Frame: Approx 6 months ] [ Designated as safety issue: No ]
• ORR in the treated area [ Time Frame: Approx 6 months ] [ Designated as safety issue: No ]
• Adverse Events [ Time Frame: Approx 6 months ] [ Designated as safety issue: Yes ]
• Resource utilization [ Time Frame: Approx 6 months ] [ Designated as safety issue: Yes ]

The purpose of this study is to evaluate overall survival in patients treated with HepaSphere/QuadraSphere compared to conventional transarterial chemoembolization with particle PVA.

• Device: HepaSphere/QuadraSphere Microspheres
  HepaSphere/QuadraSphere Microspheres loaded with doxorubicin
• Procedure: PVA, lipiodol, doxorubicin
  Conventional TACE procedure using PVA, lipiodol and doxorubicin

• Experimental: HepaSphere/QuadraSphere TACE
  HepaSphere/QuadraSphere TACE
  Intervention: Device: HepaSphere/QuadraSphere Microspheres
• Active Comparator: Conventional TACE
  Conventional TACE
  Intervention: Procedure: PVA, lipiodol, doxorubicin

Inclusion Criteria:

Patients must meet all of the following inclusion criteria in order to be entered into the study:

1. Age 18 or older
2. Patient has signed informed consent
3. Patient must have a diagnosis of hepatocellular cancer confirmed by at least one of the following:

i. Histological confirmation ii. Magnetic resonance imaging (MRI) result consistent with cirrhosis AND at least one solid liver lesion >2 cm with early enhancement and delayed enhancement washout, regardless of alpha fetoprotein level iii. Alpha fetoprotein level >400 ng/mL AND evidence of at least one solid liver lesion >2 cm, regardless of specific imaging characteristics on MRI

d. Patient must not be suitable for treatment by resection or percutaneous ablation at time of study entry.

Patients not suitable for ablation due to lesion location may be enrolled

e. Patient MUST meet at least ONE of the following criteria:

i. Stage Child-Pugh B 7 ii. Recurrent HCC iii.Performance status ECOG 1

f. Patient has a life expectancy of at least 6 months

g. Absence of occlusive thrombus to the main portal trunk

Exclusion Criteria:

If patients meet any of the following criteria they may not be entered into the study:

1. Current or previous treatment with chemo- or radiation therapy or sorafenib
2. Previous treatment with any form of transarterial embolization for HCC
3. Patients with current or history of any other cancer except non-melanomatous skin cancer
4. Female patients who are pregnant, breastfeeding, or premenopausal and not using an effective method of contraceptive
5. Performance status ECOG > 2
6. Child-Pugh scores >7
7. Active gastrointestinal bleeding
8. Evidence of uncorrectable bleeding diathesis
9. Extra-hepatic spread of the HCC
10. Total Bilirubin > 3 mg/dL
11. >50% tumor involvement of the liver
12. Infiltrative or diffuse HCC
13. Encephalopathy not adequately controlled medically
14. Presence of ascites not controlled medically
15. Presence of medically relevant localized or systemic infection, other than hepatitis B, C, D, E or G
16. Any contraindication for MRI (eg. metallic implants)
17. Allergy to contrast media that cannot be managed with prophylaxis
18. Allergy to iodized oil
19. Any contraindication to arteriography
20. Any contraindication for doxorubicin administration, including the following:

i. White Blood Cell count (WBC) <3000 cells/mm₃

ii. Absolute Neutrophil <1500 cells/mm₃

iii. Cardiac ejection fraction <50%

iv. Other condition deemed exclusionary by physician

u. Any contraindication for hepatic embolization, including the following:

i. Porto-systemic shunt, or an arteriovenous shunt that cannot be adequately closed prior to chemoembolization

ii. Hepatofugal blood flow

iii. Serum creatinine > 2mg/dL

iv. Uncorrectable impaired clotting

1. Platelet <50,000/mm₃
2. International Normalized Ratio (INR) > 1.4

3. Activated Prothrombin Time (aPTT) outside normal limits

   v. AST > 5X upper limit of normal for lab

   vi. ALT > 5X upper limit of normal for lab