Phase II Study of Concurrent Sorafenib and Intensity-modulated Radiotherapy (IMRT) for Advanced Hepatocellular Carcinoma
Condition: Hepatocellular Carcinoma, Radiotherapy, Sorafenib
MeSH terms: Carcinoma; Carcinoma, Hepatocellular
Study type: Interventional
Phase: Phase 2

Summary: 
      This is a single-arm phase II clinical trial to investigate the efficacy and toxicity of
      concurrent sorafenib and intensity-modulated radiotherapy (IMRT) for advanced hepatocellular
      carcinoma with portal vein or hepatic vein tumor thrombosis or lymph node involved.
      Eligibility patients will receive IMRT to hepatic primary tumor, vein tumor thrombosis, and
      metastasis lymph node with concurrently sorafenib with a dose of 400mg twice daily.
      Prescription of IMRT will be a conventional fraction dose of 2Gy to a total dose of 40 to
      60Gy. Sorafenib will be maintained with a dose of 400mg twice daily after IMRT until disease
      progression, or unacceptable adverse events. Six months of sorafenib maintenance is
      recommended.
    

Detailed description: 
      With the clinical application of three-dimensional conformal radiotherapy (3DCRT) and
      intensity modulated radiotherapy (IMRT), radiotherapy (RT) has shown important role in the
      treatment of hepatocellular carcinoma (HCC). Meta-analysis has demonstrated that
      transcatheter arterial chemoembolization (TACE) combined RT was more therapeutically
      beneficial than TACE alone. Especially for advanced disease with portal vein tumor thrombosis
      (PVTT), or hepatic vein tumor thrombosis, or lymph node involved, RT was more effective than
      other treatment methods. Previous studies had showed that RT could receive response rate of
      50% to 60% for HCC with PVTT. But for those patients, high accidence of out RT field failure
      of liver and distance metastasis was found. Effective systemic therapy was necessary to
      advanced HCC. Based on two phase III trials, sorafenib was recommended as systemic therapy to
      advanced HCC. But tumor response rate of sorafenib alone was only 2.3-3% by RICIST criteria.
      More than half of patients was received survival benefit by maintaining in stable disease. It
      is feasible to improve survival by combining IMRT and sorafenib for advanced HCC with portal
      vein tumor thrombosis (PVTT), or hepatic vein tumor thrombosis, or lymph node involved. In
      addition, it was demonstrated that sorafenib could potentiate irradiation in HCC cell lines
      through inhibiting radiation-induced proliferation and DNA repair and promoting
      radiation-induced apoptosis.
    

Intervention name(s): concurrent sorafenib and IMRT, followed sorafenib maintenance
Intervention type(s): Radiation
Intervention description(s): IMRT 40-60Gy/20-30f; concurrent sorafenib 400mg bid po (it can be given to patients in four weeks before IMRT is applied, so that it can control disease during waiting for IMRT); maintenance sorafenib 400mg bid po until disease progress or unacceptable adverse events; six months is recommended but not mandatory.
Intervention MeSH terms: Sorafenib
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: hepatocellular carcinoma; intensity-modulated radiotherapy; sorafenib; portal vein thrombosis; lymph node metastasis