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

About this trial
This is an interventional treatment trial for Hepatocellular Carcinoma focused on measuring Liver, HCC
Eligibility Criteria
Inclusion Criteria
- Age: 18-85 years
- Diagnosis of hepatocellular carcinoma
If primary diagnosis of HCC: diagnosis based on the following criteria:
- cyto-histological criteria, OR
- radiological criteria: Focal lesion >1 cm with arterial hypervascularization in 2 coincident imaging techniques (CT, MRI, or US), OR
- combined criteria: one imaging technique showing a focal lesion 1-2 cm with arterial hypervascularization AND AFP levels >400 ng/mL, OR
- combined criteria: one imaging technique showing a focal lesion >2 cm with arterial hypervascularization AND AFP levels >200 ng/mL
- If extrahepatic metastases: liver-dominant disease
- Stage BCLC A, B, or C
- 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)
- Willing to comply with all study procedures
- Has voluntarily given written informed consent
Exclusion Criteria
- 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)
- If male, not using adequate birth control measures
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
- Life expectancy <16 weeks or medically unstable
- 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)
- Patients with known GFR <30 mL/min/1.73m2
- 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)
- Uncontrolled infections at the time of microtherapy
- 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)
- Uncontrolled ascites
- Tumor load of the whole liver >70%
- 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)
- Prior resection of the papilla of Vater (e.g., Whipple procedure) or bile duct stent across the papilla
- 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
- Uncontrolled hypertension
- 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).
- History of GI bleeding within 30 days before inclusion into this study
- History of esophageal varices bleeding which has not been controlled by effective therapy and/or therapy to prevent bleeding recurrence
- Previous malignancy other than carcinoma in situ of the skin or the cervix uteri within 5 years prior to inclusion
- History of organ transplant (including prior liver transplantation)
- HIV, congenital immune defect, any immunosuppressive therapy for autoimmune disease (rheumatoid arthritis) or inflammatory bowel disease
- Mental conditions rendering the subject incapable to understand the nature, scope, and consequences of the trial
- Close affiliation with the investigational site; e.g. first-degree relative of the investigator
- Participating in another therapeutic clinical trial or has completed study participation in another therapeutic clinical trial within 30 days of enrolment into this trial
- Having been previously enrolled in this clinical trial
Sites / Locations
- University of Magdeburg
Arms of the Study
Arm 1
Arm 2
Other
Active Comparator
local ablation group
palliative treatment group
Local ablation group: Potentially curative treatment of early HCC includes surgical resection and local ablation (RFA, PEI, BT). Recurrence rates after such approaches are reported to amount to 50% at 3 years and 70% at 5 years. Tumor recurrence may be either due to de novo development of new primary tumors or due to intrahepatic (unrecognized) metastases. Prevention of recurrence after local ablation is an important strategy to improve overall survival. So far, adjuvant chemoembolization and chemotherapy have not proven to be effective in preventing recurrences. There is, however, a strong rationale to assume that sorafenib will be of value in the adjuvant treatment of HCC as sorafenib has a dual mechanism of action (inhibition of tumor proliferation and antiangiogenesis) and has proven efficacy in HCC.
Radioembolization has been reported to be effective in patients with unresectable HCC with preserved liver function from a number of trials. Successful downstaging of disease rendering patients eligible for potentially curative therapies, and even histologically confirmed complete responses of unresectable HCC, have repeatedly been reported providing the rationale to evaluate SIRT+sorafenib in comparison to sorafenib alone. The impact of cirrhosis as a concomitant disease in most patients with HCC is that it limits the ability of many patients to tolerate chemotherapy and is an independent cause of death in HCC patients. Thus, the historical difficulty in demonstrating an effect of therapy on survival in patients with advanced-stage, unresectable HCC (the majority). A new therapy that is effective in controlling hepatic disease, is less toxic than traditional chemotherapy, and improves the quality of life for patients in the advanced stages of HCC could represent an alternative.