Patients with Hepatocellular carcinoma (liver-predominant disease) MedDRA version: 20.0 Level: LLT Classification code 10019829 Term: Hepatocellular carcinoma recurrent System Organ Class: 100000004864 MedDRA version: 20.0 Level: LLT Classification code 10019828 Term: Hepatocellular carcinoma non-resectable System Organ Class: 10000000
Conditions
Interventions
Trade Name: Nexavar
Pharmaceutical Form: Tablet
INN or Proposed INN: SORAFENIB tosylate
CAS Number: 284461-73-0
Concentration unit: mg m
Sponsors
Medical Faculty, University Magdeburg
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age: 18-85 years 2. Hepatocellular carcinoma 3. If extrahepatic metastases: liver-dominant disease 4. Stage BCLC A, B, or C 5. Child-Pugh A, Child-Pugh B up to 7 points 6. Willing to comply with all study procedures 7. Has voluntarily given written informed consent Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 222 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 443
Exclusion criteria
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 2 4. Life expectancy 1.5 times the upper limit of normal 8. uncontrolled infections at the time of microtherapy 9. Child-Pugh score >7 points; 10. Uncontrolled ascites 11. tumor load of the whole liver >70% 12. Contraindications for study medications according to product labeling or procedures 13. Having undergone surgical procedures with resection of the sphincter of Oddi 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. In patients in whom local ablation therapy is appropriate (local ablation group), to determine if the sorafenib in combination with tumor ablation (collectively termed RFA) prolongs the time-to-recurrence (TTR) in comparison with RFA + placebo. 2. In patients in whom tumor ablation is NOT appropriate (palliative treatment group), to determine if the combination of yttrium-90 microspheres (SIRT) + sorafenib improves the overall survival (OS) in comparison to sorafenib alone. 3. To confirm in a 2-step procedure that Primovist-enhanced MRI is non-inferior (first step) or superior (second step) compared with contrast-enhanced multislice CT for stratification of patients to a palliative vs. local ablation treatment strategy. ; Secondary Objective: • to assess health-related quality of life • to compare the number of detected lesions and the diagnostic confidence in Primovist-enhanced MRI with contrast-enhanced CT • to compare Primovist-enhanced MRI with contrast-enhanced CT regarding the detection of recurrence (patients in the local ablation group only) • to assess the safety of the combination of RFA + sorafenib in comparison to RFA + placebo • to assess the safety of the combination of SIR-Spheres therapy and sorafenib in comparison to sorafenib alone • to assess in the palliative study group overall survival separately for patients with and without portal thrombosis ; Primary end point(s): • TTR (local ablation group) • Overall Survival (palliative treatment group) • number of correct assignments to a local ablation / palliative treatment strategy (diagnostic part of the study) ;Timepoint(s) of evaluation of this end point: end of trial | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • to assess health-related quality of life • to compare the number of detected lesions and the diagnostic confidence in Primovist-enhanced MRI with contrast-enhanced CT • to compare Primovist-enhanced MRI with contrast-enhanced CT regarding the detection of recurrence (patients in the local ablation group only) • to assess the safety of the combination of RFA + sorafenib in comparison to RFA + placebo • to assess the safety of the combination of SIR-Spheres therapy and sorafenib in comparison to sorafenib alone • to assess in the palliative study group overall survival separately for patients with and without portal thrombosis ;Timepoint(s) of evaluation of this end point: overall survival: two interim analyses are planned: at 80 and 160 deaths | — |
Countries
Austria, Belgium, Germany, Italy, Netherlands, Poland, Slovenia, Spain, Switzerland, Turkey, United Kingdom
Contacts
Public ContactStudy Lead
pharmtrace klinische Entwicklung GmbH
Outcome results
None listed