Erlotinib Plus Bevacizumab in Hepatocellular Carcinoma (HCC) as Second-line Therapy

Inclusion Criteria: 1. Patients with histological or cytologically documented HCC not amenable to curative resection (documentation of original biopsy for diagnosis is acceptable if tumor tissue is unavailable) or clinical diagnosis by American Association for the Study of Liver Diseases (AASLD) criteria in cirrhotic subjects is required. For subjects without cirrhosis, histological or cytological confirmation is mandatory. 2. Patients must have measurable disease as per the modified RECIST criteria. Measurable target lesions are defined at baseline as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) \>/= 20 mm using conventional techniques (CT or MRI) or \>/= 10 mm using spiral CT scan. Lesion must not be chosen from a previously irradiated field, unless there has been documented disease progression in that field after irradiation. 3. Patients who have progressed on, or were intolerant to, one prior systemic therapy with sorafenib, completed ≥ 14 days prior to treatment day 1. Previous treatments also allowed that do not count as systemic therapy include: surgical resection, transarterial embolization/chemoembolization (TAE/TACE), radiofrequency ablation (RFA), percutaneous ethanol injection (PEI), provided that the lesion(s) to be evaluated in this study are separate from the previously treated lesions(s). 4. Eastern Cooperative Oncology Group (ECOG) performance status of \</= 2. 5. Childs-Pugh liver function status of A or B (only 7 points allowed). 6. Organ function: Absolute peripheral granulocyte count of \>/= 1500 mm\^3, platelet count of \>/= 40,000 mm\^3, hemoglobin \>/= 10 gm/dL. Total bilirubin \</= 2.0 gm/dL; serum albumin \>/= 2.5 gm/dL; aspartate aminotransferase (AST) and alanine aminotransferase (ALT) up to 5 X the upper limit of institutional normal (AST - 46 and ALT - 56); and prothrombin time prolonged not more than 3 seconds greater than institutional normal, once attempts to correct a prolonged PT have been made. 7. (Continuation of # 6) Patients who require full dose anticoagulation, who are otherwise eligible for this trial, are allowed to have an appropriately prolonged International Normalized Ratio (INR). 8. Negative serum pregnancy test in women with childbearing potential (those who are not surgically sterilized or who are not amenorrheic for \>/= 12 months), within one week prior to initiation of treatment. 9. Men and women of childbearing potential must agree to use effective means of contraception prior to study entry and for at least 180 days after the last dose of study treatment. They must agree to use two forms of birth control, for example, barrier methods (such as a diaphragm, cervical cap, contraceptive sponge, female condom, or male condom), and an intrauterine device (IUD). 10. Age \>/= 18 years. The agents bevacizumab and erlotinib have not been studied in pediatric patients, thus the doses to be used in this study cannot be assumed to be safe in children. 11. Radiographic evidence of disease progression during or following prior treatment with sorafenib. 12. Patients must have proteinuria \< 2+ or a urine protein:creatinine (UPC) ratio \< 1.0. Patients who have proteinuria \>/= 2+ and UPC ratio \>/= 1.0 must undergo a 24 hour urine collection and must demonstrate \</= 1g of protein in 24 hours to be eligible. Exclusion Criteria: 1. Patients who have had prior systemic therapy other than sorafenib. Patients may not have received any systemic chemotherapy \</=14 days of Treatment Day 1. 2. Active malignancy other than superficial basal cell and superficial squamous (skin) cell, or carcinoma in situ of the cervix within last five years. 3. Current, recent (within 4 weeks of Treatment Day 1) or planned participation in an experimental drug study, other than this study. 4. Gastrointestinal disease resulting in an inability to take oral medication or a requirement for intravenous hyperalimentation. 5. History of rupture of existing HCC lesion, or HCC lesion with large necrotic areas seen on conventional imaging studies, as determined by the Principal Investigator, if there is no measurable solid tumor area \> 1.5 cm. 6. Inadequately controlled hypertension (defined as systolic blood pressure \>140 and/or diastolic blood pressure \> 90). 7. Prior history of hypertensive crisis or hypertensive encephalopathy. 8. New York Heart Association Class II or greater congestive heart failure. 9. Cardiac arrhythmia not controlled by medication. 10. History of myocardial infarction or unstable angina within 6 months of Treatment Day 1. 11. History of stroke or transient ischemic attack within 6 months prior to Day 1 of treatment. 12. Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Day 1. 13. Evidence of clinically significant \[Common Terminology Criteria (CTC) Grade 3 or 4\] venous or arterial thrombotic disease within previous 6 months. 14. Radiographic evidence of major tumor thrombus in the vena cava. 15. History of hemoptysis (\>/= 1/2 teaspoon of bright red blood per episode) within 1 month prior to Day 1. 16. Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation). 17. History of significant gastrointestinal bleeding requiring procedural intervention (eg variceal banding, Transjugular Intrahepatic Portosystemic Shunts (TIPS) procedure, arterial embolization) within three months prior to treatment day 1. Patients at risk for varices (based on the following: known history of esophageal or gastric varices; evidence of hepatic cirrhosis and/or portal hypertension including biopsy-proven cirrhosis, radiographic evidence of cirrhosis, hypersplenism, or radiographic findings of varices) will be screened for esophageal varices. 18. (Continuation of # 17) If varices are identified that require intervention (banding), that patient will not be eligible for the trial until the varices have been adequately treated. 19. Known CNS disease, except for treated brain metastases. Treated brain metastases are defined as having no evidence of progression or hemorrhage after treatment and no ongoing requirement for dexamethasone, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period. Anticonvulsants (stable dose) are allowed. Treatment for brain metastases may include whole brain radiotherapy (WBRT), radiosurgery (RS; Gamma Knife, linear accelerator (LINAC), or equivalent) or a combination as deemed appropriate by the treating physician. 20. (Continuation of # 20) Patients with CNS metastases treated by neurosurgical resection or brain biopsy performed within 3 months prior to Day 1 will be excluded. 21. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1, or anticipation of need for major surgical procedure during the course of the study. 22. Core biopsy, fine needle aspiration, or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to Day 1. 23. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 1. 24. Serious, non-healing wound, active ulcer, or untreated bone fracture. 25. 0ngoing or active infection requiring parenteral therapy. 26. Known HIV disease. 27. Uncontrolled psychiatric illness. 28. Known hypersensitivity to any component of bevacizumab and erlotinib. 29. Pregnancy (positive pregnancy test) or lactation. 30. Inability to comply with study and/or follow-up procedures.