RTOG 1112: This phase III trial is trying to determine how well radiotherapy and an oral drug (sorafenib tosylate) work together in the treatment of patients with liver cancerRandomized Phase III Study of Sorafenib Versus Stereotactic Body Radiation Therapy Followed by Sorafenib in Hepatocellular Carcinoma

Inclusion

• Patients must have a diagnosis of HCC by at least one criterion listed below within 360 days prior to study entry:

  • Pathologically (histologically or cytologically) proven diagnosis of HCC,(biopsies are recommended, and are to be submitted for research evaluation if patients consent)
  • At least one solid liver lesion or vascular tumor thrombosis (involving portal vein, inferior vena cava (IVC) and/or hepatic vein) > 1 cm with arterial enhancement and delayed washout on multi-phasic computerized tomography (CT) or magnetic resonance imaging (MRI) in the setting of cirrhosis or chronic hepatitis B or C without cirrhosis.
  • For patients whose CURRENT disease is vascular only: enhancing vascular thrombosis (involving portal vein, IVC and/or hepatic vein) demonstrating early arterial enhancement and delayed washout on multi-phasic CT or MRI in a patient with known HCC (diagnosed previously <720 days) using the above criteria.
• Measureable hepatic disease and/or presence of vascular tumor thrombosis (involving portal vein, IVC and/or hepatic vein) which may not be measureable as per Response Evaluation Criteria in Solid Tumors (RECIST) on liver CT or MRI, within 28 days of registration

• Appropriate for protocol entry based upon the following minimum diagnostic workup:

  • History/physical examination including examination for encephalopathy, ascites, weight, height, and blood pressure within 14 days prior to study entry
  • Assessment by radiation oncologist and medical oncologist or hepatologist who specializes in treatment of HCC within 28 days prior to study entry
  • Pre-randomization Scan (REQUIRED for All Patients): Within 28 days prior to study entry, multiphasic liver CT or multiphasic liver MR scan.
  • Within 28 days prior to study entry CT chest with CT or MR abdomen and CT or MR pelvis, or positron emission tomography (PET) CT chest/abdomen/pelvis.
• Zubrod performance status 0-2 within 28 days prior to study entry

• All blood work obtained within 14 days prior to study entry with adequate organ marrow function defined as follows:

  • Absolute neutrophil count (ANC) >= 1,500 cells/mm^3
  • Platelets >= 60,000 cells/mm^3
  • Hemoglobin >= 8.0 g/dl (note: the use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 8.0 g/dl is acceptable)
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 6 times upper limit of normal (ULN)
  • Serum creatinine =< 2 x ULN or creatinine clearance >= 60 mL/min
• Barcelona Clinic Liver Cancer (BCLC) stage: intermediate (B) or advanced (C) within 28 days prior to study entry
• Child-Pugh score A within 14 days prior to study entry
• Women of childbearing potential and male participants must agree to practice adequate contraception while on study and for at least 6 months following the last dose of radiation therapy (RT) and for at least 28 days following the last dose of sorafenib (whichever is later)
• Unsuitable for resection or transplant or radiofrequency ablation (RFA)

• Unsuitable for or refractory to transarterial hepatic chemo-embolization (TACE) or drug eluting beads (DEB) for any of the following reasons, as described by Raoul et al (2011):

  • Technical contraindications: arteriovenous fistula, including, surgical portosystemic shunt or spontaneous portosystemic shunt
  • Severe reduction in portal vein flow: due to tumor portal vein, IVC or atrial invasion or bland portal vein occlusion
  • Medical contraindications including congestive heart failure, angina, severe peripheral vascular disease
  • Presence of extrahepatic disease
  • No response post TACE (or DEB) or progressive HCC despite TACE; prior TACE or DEB is allowed but must be > 28 days from study entry
  • Serious toxicity following prior TACE (or DEB); prior TACE or DEB must be > 28 days from study entry
  • Other medical comorbidities making TACE (or DEB) unsafe and/or risky (e.g. combination of relative contraindications including age > 80 years, tumor > 10 cm, > 50% replacement of the liver by HCC, extensive multinodular bilobar HCC, biliary drainage)
• Patients treated with prior surgery are eligible for this study if they otherwise meet eligibility criteria
• Patient must be able to provide study-specific informed consent prior to study entry