Sorafenib with or without Stereotactic Body Radiation Therapy in Treating Patients with Liver Cancer

Inclusion Criteria

• Patients must have an HCC diagnosis (initial, recurrent, progressive and/or refractory to other therapies) by at least one criterion listed below =< 360 days prior to study entry * Pathologically (histologically or cytologically) proven diagnosis of HCC * 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)
• Patients must have measurable hepatic disease and/or presence of vascular tumor thrombosis (involving portal vein, IVC and/or hepatic vein) which may not be measurable as per Response Evaluation Criteria in Solid Tumors (RECIST) on liver CT or MRI, within 28 days PRIOR TO STUDY ENTRY
• 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 magnetic resonance (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
• Age >= 18
• Absolute neutrophil count (ANC) >= 1,500 cells/mm^3 (obtained within 14 days prior to study entry)
• Platelets >= 60,000 cells/mm^3 (obtained within 14 days prior to study entry)
• Hemoglobin >= 8.0 g/dl (Note: the use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 8.0 g/dl is acceptable) (obtained within 14 days prior to study entry)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 6 times upper limit of normal (ULN) (obtained within 14 days prior to study entry)
• Serum creatinine =< 2 x ULN or creatinine clearance >= 60 mL/min (obtained within 14 days prior to study entry)
• Patients must have 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 (using international normalized ratio [INR] from < 28 days is acceptable)
• 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

Exclusion Criteria

• Prior invasive malignancy (except non-melanomatous skin cancer and T1 renal cell carcinoma) unless disease free for a minimum of 2 years (note that carcinoma in situ of the breast, oral cavity, or cervix are all permissible)
• Prior sorafenib use > 60 days and/or grade 3 or 4 sorafenib related toxicity; note that prior chemotherapy for HCC or a different cancer is allowable
• Prior radiotherapy to the region of the liver that would result in excessive doses to normal tissues due to overlap of radiation therapy fields
• Prior selective internal radiotherapy/hepatic arterial yttrium therapy, at any time
• Severe, active co-morbidity, defined as follows: * Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months PRIOR TO registration * Transmural myocardial infarction within the last 6 months prior to study entry * Unstable ventricular arrhythmia within the last 6 months prior to study entry * Acute bacterial or fungal infection requiring intravenous antibiotics within 28 days prior to study entry * Hepatic insufficiency resulting in clinical jaundice, encephalopathy and/or variceal bleed within 28 days prior to study entry * Bleeding within 28 days prior to study entry due to any cause, requiring transfusion * Thrombolytic therapy within 28 days prior to study entry; subcutaneous heparin is permitted * Known bleeding or clotting disorder * Uncontrolled psychotic disorder
• Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic
• Maximal diameter of any one hepatocellular carcinoma > 15 cm
• Total sum of maximum diameters of each definite parenchymal hepatocellular carcinomas within the liver or maximum diameter of a single conglomerate HCC > 20 cm
• More than 5 discrete intrahepatic parenchymal foci of definite HCC
• Direct tumor extension into the stomach, duodenum, small bowel or large bowel
• Measurable common or main branch biliary duct involvement with HCC
• Extrahepatic metastases or malignant nodes (that enhance with typical features of HCC) > 3.0 cm, in sum of maximal diameters (e.g. presence of one 3.4 cm metastatic lymph node or two 2 cm lung lesions); note that benign non-enhancing periportal lymphadenopathy is not unusual in the presence of hepatitis and is permitted, even if the sum of enlarged nodes is > 2.0 cm
• Prior liver transplant
• Human immunodeficiency virus (HIV) positive with CD4 count < (350) cells/microliter; note that patients who are HIV positive are eligible, provided they are under treatment with highly active antiretroviral therapy (HAART) and have a CD4 count >= (350) cells/microliter, and no known detectable viral load, at the time of study entry; note also that HIV testing is not required for eligibility for this protocol