Sorafenib and Bavituximab Plus SBRT in Unresectable Hepatocellular Carcinoma

Inclusion Criteria:

* Advanced, unresectable hepatocellular carcinoma (unsuitable for resection, transplant or ablation)
* Age ≥ 18
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
* Must have normal organ and marrow function
* Childs-Pugh score of A or B7
* Must have measurable/evaluable disease as per RECIST 1.1 criteria
* Females of child-bearing potential must agree to use dual methods of contraception and have a negative serum pregnancy test at screening, and male patients must use an effective barrier method of contraception if sexually active with a female of child-bearing potential. For both males and females, effective methods of contraception must be used throughout the study and for four months following the last dose.
* Able to swallow and retain orally administered medication and does not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels.
* Must be able to understand and be willing to sign the written informed consent form
* No more than 10 lesions in the liver

Exclusion Criteria:

* Have received radiation therapy, major surgery, other locoregional therapy, within 4 weeks prior to the first date of SBRT
* 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
* Any one hepatocellular carcinoma \> 15 cm
* Total maximal sum of hepatocellular carcinomas or a single conglomerate HCC \> 20 cm
* Direct tumor extension into the stomach, duodenum, small bowel or large bowel
* Measureable 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.
* Use of regular phenytoin, carbamazepine, hypericum perforatum \[also known as St. John's wort\] or rifampin
* Have received sorafenib or other systemic therapies for treatment of HCC in the past.
* Active autoimmune disease; Patients with type I diabetes mellitus, hypothyroidism requiring only hormone replacement, psoriasis not requiring systemic treatment, or vitiligo are permitted for enrollment.
* No active malignancy except for nonmelanoma skin cancer or in situ cervical cancer. Patients surviving a cancer that was curatively treated and without evidence of disease for more than 3 years before the trial are allowed.
* Myocardial infarction within past 6 months, congestive heart failure, unstable angina, active cardiomyopathy, unstable ventricular arrhythmia
* Congenital long QT syndrome
* Previous stroke within past 12 months
* Anti-coagulant therapy, bleeding or clotting disorder
* Symptomatic metastatic brain or meningeal tumors
* Presence of a non-healing wound, non-healing ulcer, or bone fracture
* History of organ allograft (including corneal transplant)
* Known or suspected allergy or hypersensitivity to any of the study drugs, study drug classes, or excipients of the formulations given during the course of this trial
* Women who are pregnant or breast-feeding
* Any condition which, in the investigator's opinion, makes the patient unsuitable for trial participation