Evaluation of Sorafenib in combination with local micro-therapy guided by Gd-EOB-DTPA enhanced MRI in patients with inoperable hepatocellular carcinoma

Phase 2

Completed

• Conditions: hepatocellular carcinoma; liver cancer; 10019815

• Registration Number: NL-OMON41292
• Lead Sponsor: Otto-von-Guericke-Universität

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 6 May 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 30

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

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. Pulmonary metastases
6. Patients with known GFR <30 mL/min/1.73m2
7. PT-INR/PTT >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

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Primary objectives<br /><br>1. In patients in whom local ablation therapy is appropriate (local ablation<br /><br>group), to determine if the sorafenib in combination with tumor ablation (RFA)<br /><br>prolongs the time-to-recurrence (TTR) in comparison with RFA + placebo.<br /><br>2. In patients in whom RFA is NOT appropriate (palliative treatment group), to<br /><br>determine if the combination of yttrium-90 microspheres (SIRT) + sorafenib<br /><br>improves the overall survival (OS) in comparison to sorafenib alone.<br /><br>3. T o confirm in a 2-step procedure that Primovist®-enhanced MRI is<br /><br>non-inferior (first step) or superior (second step) compared with<br /><br>contrast-enhanced multislice CT for assignment of patients to a palliative vs.<br /><br>local ablation treatment strategy.<br /><br>The overall study is successful if the primary objectives 1 OR 2 are met AND<br /><br>Primovist®-enhanced MRI is at least non-inferior to contrast-enhanced CT for<br /><br>treatment decisions.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Secondary objectives<br /><br>1.To assess health-related quality of life<br /><br>2.To compare the number of detected lesions and the diagnostic confidence in<br /><br>Primovist-enhanced MRI with contrast-enhanced CT<br /><br>3.To compare Primovist-enhanced MRI with contrast-enhanced CT regarding the<br /><br>detection of recurrence (patients in the local ablation study group only)<br /><br>4.To assess the safety of the combination of RFA + sorafenib in comparison to<br /><br>RFA + placebo<br /><br>5.To assess the safety of the combination of SIR-Spheres and sorafenib therapy<br /><br>in comparison to sorafenib therapy alone<br /><br>6.To assess in the palliative study group overall survival separately for<br /><br>patients with and without portal thrombosis</p><br>