Sorafenib and Micro-therapy Guided by Primovist Enhanced MRI in Patients With Inoperable Liver Cancer (SORAMIC)

Inclusion Criteria

1. Age: 18-85 years
2. Diagnosis of hepatocellular carcinoma

3. If primary diagnosis of HCC: diagnosis based on the following criteria:

   1. cyto-histological criteria, OR
   2. radiological criteria: Focal lesion >1 cm with arterial hypervascularization in 2 coincident imaging techniques (CT, MRI, or US), OR
   3. combined criteria: one imaging technique showing a focal lesion 1-2 cm with arterial hypervascularization AND AFP levels >400 ng/mL, OR
   4. combined criteria: one imaging technique showing a focal lesion >2 cm with arterial hypervascularization AND AFP levels >200 ng/mL
4. If extrahepatic metastases: liver-dominant disease
5. Stage BCLC A, B, or C
6. Child-Pugh A, Child-Pugh B up to 7 points (in patients receiving anticoagulant therapy: Child-Pugh score up to 5 points; INR category not regarded for calculation of the Child-Pugh score)
7. Willing to comply with all study procedures
8. Has voluntarily given written informed consent

Exclusion Criteria

1. If female, pregnant or breast feeding (females of child-bearing potential must use adequate contraception and must have a negative pregnancy test performed within 7 days prior to inclusion into this study)
2. If male, not using adequate birth control measures

3. One or more of the following:

   • Hemoglobin <10g/dL,
   • WBC <2,500 cells/mm3,
   • ANC <1,500 cells/mm3,
   • platelets <50,000/mm3,
   • ECOG performance status >2
4. Life expectancy <16 weeks or medically unstable
5. Extrahepatic metastases (except metastases to bone, lymph nodes, and adrenal glands which do not constitute an exclusion criterion), but, see Additional Criteria for the Local Ablation Group, below (Section 4.2 of the study protocol)
6. Patients with known GFR <30 mL/min/1.73m2
7. PT-INR/PTT >1.5 times the upper limit of normal (patients on anticoagulation therapy will be allowed to participate provided that no prior evidence exists of an underlying abnormality in anticoagulation)
8. Uncontrolled infections at the time of microtherapy
9. Child-Pugh score >7 points; in patients receiving anticoagulant therapy: Child-Pugh score >5 points (INR category not regarded for calculation of the Child-Pugh score)
10. Uncontrolled ascites
11. Tumor load of the whole liver >70%
12. Contraindications for study medications according to product labeling or procedures (sorafenib, Primovist®, x-ray contrast agents, SIR-Spheres®, RFA, MWA, MRI, CT) incl. any contraindication to the transarterial interventional procedure (e.g., allergy against x-ray contrast agents, uncontrolled hyperthyroidism)
13. Prior resection of the papilla of Vater (e.g., Whipple procedure) or bile duct stent across the papilla
14. Significant cardiovascular disease; e.g., myocardial infarction within 6 months of inclusion, chronic heart failure (New York Heart Association class III or IV), unstable coronary artery disease
15. Uncontrolled hypertension
16. Thrombotic or embolic events including transient ischemic attacks within the past 6 months (tumor-related portal vein thrombosis allowed in the palliative part of the trial).
17. History of GI bleeding within 30 days before inclusion into this study
18. History of esophageal varices bleeding which has not been controlled by effective therapy and/or therapy to prevent bleeding recurrence
19. Previous malignancy other than carcinoma in situ of the skin or the cervix uteri within 5 years prior to inclusion
20. History of organ transplant (including prior liver transplantation)
21. HIV, congenital immune defect, any immunosuppressive therapy for autoimmune disease (rheumatoid arthritis) or inflammatory bowel disease
22. Mental conditions rendering the subject incapable to understand the nature, scope, and consequences of the trial
23. Close affiliation with the investigational site; e.g. first-degree relative of the investigator
24. Participating in another therapeutic clinical trial or has completed study participation in another therapeutic clinical trial within 30 days of enrolment into this trial
25. Having been previously enrolled in this clinical trial