TRC105 and Sorafenib Tosylate in Treating Patients with Liver Cancer

Inclusion Criteria

• Patients must have histopathological confirmation of hepatocellular carcinoma (HCC) by the Laboratory of Pathology of the National Cancer Institute (NCI) prior to entering this study OR
• Histopathological confirmation of carcinoma in the setting of clinical and radiological characteristics which, together with the pathology, are highly suggestive of a diagnosis of HCC
• Patients must have disease that is not amenable to potentially curative resection or ablative techniques; in addition, disease must not be amenable to or have progressed on transhepatic arterial chemoembolization (TACE); patients must not be considered potential candidates for liver transplantation; this determination will be made after hepatobiliary surgical input at the NCI multidisciplinary conference
• If liver cirrhosis is present, patient must have a Child-Pugh A or B (7 points) classification
• Patients with cirrhosis must have had esophagogastric endoscopy within the previous 6 months prior to study entry for the assessment of varices; if the patient has not had this done they must be willing to undergo this procedure prior to study entry
• Life expectancy of greater than 3 months
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Absolute neutrophil count >= 1,500/mcL
• Platelets >= 60,000/mcL without transfusion support within the past 30 days
• Total bilirubin =< 3 mg/dl
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 10 × upper limit of normal
• Creatinine =< 1.5 x upper normal limits OR creatinine clearance >= 40 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal, as calculated by the Cockcroft Gault formula
• Patients must have recovered from any acute toxicity related to prior therapy, including surgery; toxicity should be =< grade 1 or returned to baseline
• Patients must not have other invasive malignancies within the past 5 years (with the exception of non-melanoma skin cancers or non-invasive bladder cancer)
• Patient must be able to understand and willing to sign a written informed consent document
• PHASE I: Patients may have measurable or evaluable disease only
• PHASE I: Prior systemic therapy with sorafenib is allowed
• PHASE II: All patients will be required to have measurable disease
• PHASE II: Prior systemic therapy with sorafenib is allowed

Exclusion Criteria

• Patients who have had chemotherapy (other than sorafenib treatment), large field radiotherapy, or major surgery must wait 4 weeks prior to entering the study
• Patients may not be receiving any agents not approved by the Food and Drug Administration (FDA) within the past 4 weeks
• Patients with known brain metastases will be excluded from this clinical trial
• Proteinuria, as demonstrated by a 24-hour protein of >= 2000 mg; urine protein will be screened by urine protein-creatinine ratio (UPC); for UPC ratio > 1.0, a 24-hour urine protein will need to be obtained and the level should be < 2000 mg for patient enrollment
• Uncontrolled intercurrent illness including, but not limited to, hypertension (systolic blood pressure [BP] > 140, diastolic BP > 90), ongoing or active systemic infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia or psychiatric illness/social situations that would limit compliance with study requirements
• No anti-coagulation therapy is allowed with the exception of low-dose aspirin
• No bleeding diathesis
• Patients with a history of bleeding varices in previous 1 year are excluded (unless patient has subsequently had a liver transplant); those with gastric varices or varices that are deemed as high risk by the endoscopist should be placed on appropriate medical therapy as advised by the gastroenterologist
• History of peptic ulcer disease or hemorrhagic gastritis within 6 months of TRC105 administration, unless patient has received adequate treatment for peptic ulcer disease or hemorrhagic gastritis and has evidence of complete resolution documented by esophagogastroduodenoscopy (EGD); mild gastritis is allowed
• Corrected QT (QTc) interval > 500 msec
• Human immunodeficiency virus (HIV)-positive patients receiving anti-retroviral therapy are excluded from this study; HIV positive patients not receiving antiretroviral therapy are excluded
• History of hypersensitivity reaction to human or mouse antibody products
• Patients with a history of familial bleeding disorders
• Patients with a history of hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome)
• Pregnancy and breast feeding are exclusion factors; enrolled patients must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, the duration of study participation and 3 months after the end of the treatment
• Patients with unhealed wounds for more than 30 days