Sorafenib and Micro-therapy Guided by Primovist Enhanced MRI in Patients With Inoperable Liver Cancer
Condition: Hepatocellular Carcinoma
MeSH terms: Carcinoma; Carcinoma, Hepatocellular
Study type: Interventional
Phase: Phase 2

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.
    


Intervention name(s): RFA; Radioembolization (SIRT)
Intervention type(s): Procedure; Procedure
Intervention description(s): A max.of 2 percutaneous RFA sessions is permitted per patient with a max.of 2 liver lesions treated in each RFA session. Randomization to sorafenib or placebo is performed after completion of RFA. Percutaneous RFA is to be performed according to the manufacturer's instructions and following as far as possible routine procedures of the participating hospital. Typically, RFA will be performed under conscious sedation, general anesthesia is permitted. After local anesthesia of the site of puncture, the applicator is positioned in the center of the lesion using ultrasound-, CT- or MR-guidance. The success of ablation is to be controlled directly after RFA using ultrasound, contrast-enhanced CT, or MR imaging. If for any reason RFA is deemed incomplete within the immediate follow-up (up to 2 weeks after the initial ablation), RFA is to be repeated once (in this case, the total (max.) number of RFA sessions will be three).
The study procedure guide will contain further instructions for RFA.; One SIRT prescription consists of the pre-treatment assessment followed by one or 2 treatment sessions The aim of pre-treatment assessment is to ensure delivery of the microspheres to the target. Evaluation includes a determination of the arterial location and any consequent necessity for coil-embolization of the gastroduodenal artery, right gastric artery and any other accessory arteries to prevent inadvertent administration of microspheres into the gastrointestinal tract or pancreas. In addition, parasitic extrahepatic supply should be coil-embolized.
Patients in whom the shunt fraction indicates potential exposure to the lung to an absorbed radiation dose of more than 30 Gy should be excluded from treatment with SIR-Spheres. Patients who are randomized to receive SIRT but who are not regarded as eligible for SIRT after the pre-treatment assessment will be switched to the sorafenib only group within the palliative treatment arm.
Other intervention name(s): Sorafenib (Nexavar 200 mg film-coated tablets),marketing authorization no.:EU/1/06/342/001; SIR Spheres Microspheres; Sorafenib (Nexavar)
Intervention MeSH terms: Sorafenib
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Liver; HCC