Study of ThermoDox With Standardized Radiofrequency Ablation (RFA) for Treatment of Hepatocellular Carcinoma (HCC)

Inclusion Criteria:

1. Male or female ≥ 18 years of age.

2. Diagnosed with a single HCC lesion ≥ 3.0 cm but ≤ 7.0 cm in maximum diameter basedon diagnosis at screening.

• Subjects meeting the American Association for the Study of Liver Disease (AASLD) criteria may be randomized without a biopsy, but will undergo a biopsyduring the RFA procedure unless contraindicated or unattainable.

• Subjects not meeting the AASLD criteria for HCC will need a biopsy to confirmHCC prior to randomization.

3. Be an appropriate candidate for receiving RFA as a medically indicated treatment asevaluated by the following factors:

• The position and accessibility of the target lesion allows for the safeadministration of multiple ablation cycles or deployments to achieve a probedwell time of ≥ 45 minutes.

• Not a candidate for surgical resection according to the local guidelines forresection and in the Investigator's judgment.

4. Child-Pugh Class A without either current encephalopathy or ascites.

5. Left Ventricular Ejection Fraction (LVEF) ≥ 50%.

6. Eastern Cooperative Oncology Group (ECOG) performance status 0.

7. Willing to sign an informed consent form, indicating awareness of theinvestigational nature of this study that is in keeping with the policies of theinstitution.

Exclusion Criteria:

1. Is scheduled for liver transplantation

2. Expected ablation volume > 30% of total liver volume or removal of 3 hepaticsegments

3. More than 1 lesion identified during baseline.

4. Have previously received therapeutic treatment for HCC outside the study protocol oris expected to receive concomitant HCC treatment prior to PFS event.

5. Have serious medical illnesses including, but not limited to, congestive heartfailure, myocardial infarction or cerebral vascular accident within the last sixmonths, or life threatening cardiac arrhythmias.

6. Have previously received any anthracycline outside the protocol

7. Have extrahepatic metastasis.

8. Have portal or hepatic vein tumor invasion/thrombosis.

9. Have body temperature >101ºF (38.3ºC) immediately prior to study treatment.

10. Baseline laboratories (repeat lab tests are permitted to evaluate eligibility duringthe Screening Period. Lab results must be within protocol range prior to studytreatment.)

• Absolute neutrophil count < 1500/mm3

• Platelet count < 75,000/mm3

• Hgb < 10.0 g/dL (unless the hemoglobin value has been stable, the subject iscardiovascularly stable, asymptomatic and judged able to withstand the RFAprocedure) Note: If clinically indicated, subjects may receive platelets orpacked red blood cell (RBC) transfusions and be re-evaluated after condition istreated.

11. Baseline Chemistry

• Serum creatinine ≥ 2.5 mg/dL or calculated creatinine clearance (CrCl) ≤25.0mL/min.

• Serum bilirubin > 3.0 mg/dL.

• Serum albumin < 2.8 g/dL.

12. Have any known allergic reactions to any of the drugs or liposomal components orintravenous imaging agents that prohibit the ability to complete the imagingrequirements.

13. Are pregnant or breast-feeding. In women of childbearing potential, a negative serumpregnancy test is required prior to study treatment.

14. Women of childbearing potential and men who are not practicing an acceptable form ofbirth control (i.e. diaphragm, cervical cap, condom, surgical sterility or birthcontrol pills. Women whose partner has or men who have undergone a vasectomy mustuse a second form of birth control).

15. Have INR > 1.5 times the institution's upper normal limit (UNL), except in subjectswho are therapeutically anticoagulated for medical conditions unrelated to HCC suchas atrial fibrillation. Subjects may be re-screened after condition is treated oranticoagulant is withheld.

16. Have contraindications to receiving doxorubicin hydrochloride (HCl).

17. Are being treated with other investigational agents.

18. Use of an investigational drug outside this study within 30 days or 5 half-lives,whichever is longer, preceding the first dose of study medication.

19. Have other concurrent malignancy (subjects with treated squamous cell carcinoma ofthe skin or basal cell carcinoma of the skin may be included), evidence ofextrahepatic cancer from their primary malignancy, or ongoing, medically significantactive infection.

20. HIV positive.

21. NYHA class III or IV functional classification for heart failure.

22. Evidence of hemachromatosis.