Sorafenib and Micro-therapy Guided by Primovist Enhanced MRI in Patients With Inoperable Liver Cancer
- Conditions
- Hepatocellular Carcinoma
- Interventions
- Procedure: RFAProcedure: Radioembolization (SIRT)
- Registration Number
- NCT01126645
- Lead Sponsor
- University of Magdeburg
- Brief Summary
The purpose of this study is to evaluate Sorafenib and local microtherapy guided by Primovist enhanced MRI in patients with inoperable liver cancer (HCC).
Methodology:
Patients with a diagnosis of hepatocellular carcinoma will receive either:
* local ablation therapy of liver lesions by radiofrequency ablation followed by sorafenib or placebo (local ablation group), or
* radioembolization (SIRT) + sorafenib or sorafenib alone (palliative treatment group).
In each study group, patients will be randomized to one of the two treatment arms following a pre-defined randomization plan. Randomization will be on a 1:1 basis in the local ablation group and on the basis of 10 (sorafenib only) : 11 (SIRT + sorafenib) in the palliative treatment group.
Patients in the local ablation group will be followed at 2 months intervals for recurrence and overall survival, patients in the palliative treatment group will be followed for overall survival. Follow-up in each study group will end 24 months after inclusion of the last patient into the respective study group.
The assignment of patients to the local ablation or palliative study group will be based on the ablative potential of RFA (local ablation if ≤4 tumors, each ≤5 cm in size). Diagnostic imaging will be used to guide this decision. The assignment to the local ablation or the palliative treatment group will be made by the local investigator.
As a sub-study, all patients will undergo Primovist®-enhanced MRI in addition to contrast-enhanced CT before assignment to one treatment group. The goal of the sub-study is to assess the value of Primovist®-enhanced MRI to correctly stratify patients for a local ablation or palliative treatment strategy. Primovist®-enhanced MRI will be compared with contrast-enhanced multislice CT using a truth panel assessment as the standard of reference. In addition, Primovist-enhanced MRI and contrast-enhanced CT will be obtained during follow-up of patients in the local ablation group to assess its potential for detection of recurrence.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 529
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description local ablation group RFA 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. palliative treatment group Radioembolization (SIRT) 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.
- Primary Outcome Measures
Name Time Method overall survival 10-15 months (average survival) In patients in whom RFA 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.
Interim analysis will be conducted after 60 and 180 deaths and a final analysis after 240 deaths.time to recurrence 13-18 months (average time to recurrence) In patients in whom local ablation therapy is appropriate, to determine if the sorafenib in combination with radiofrequency ablation (RFA) prolongs the time-to-recurrence (TTR) in comparison with RFA + placebo.
Primovist®-enhanced MRI is non-inferior or superior compared with contrast-enhanced multislice CT 3 years 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 assignment of patients to a palliative vs. local ablation treatment strategy.
The overall study is successful, if the primary objectives 1 OR 2 are met, AND Primovist-enhanced MRI is at least non-inferior to contrast-enhanced CT for treatment stratification.
- Secondary Outcome Measures
Name Time Method safety of RFA 3 years To assess the safety of the combination of RFA + sorafenib in comparison to RFA + placebo
safety of SIR Spheres 3 years To assess the safety of the combination of SIR-Spheres therapy and sorafenib in comparison to sorafenib alone.
quality of life 3 years assess health-related quality of life via ECOG questionnaire
Trial Locations
- Locations (1)
University of Magdeburg
🇩🇪Magdeburg, Germany