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Inclusion Criteria:

1. Male or female, age \> or = 18 years with HCC refractory to currently available therapies.
2. Documented HCC by at least 2 out of 3 mentioned criteria and evidence of non-resectability by a multidisciplinary team:

   A. Radiological - MRI with arterial enhancement and rapid venous washout B. Biopsy C. Serum alpha-fetoprotein level \> or = 200
3. Positive staining for RB-function on tumor biopsy.
4. Subject must be able to give written informed consent and be able to follow protocol requirements
5. Life expectancy greater than 3 months
6. Be Child's-Pugh class A or B
7. ECOG Performance status of \< or = 2
8. If female of childbearing potential must have negative pregnancy test at screening and may not be breast-feeding
9. Females of child-bearing potential (\< one year post-menopausal with documented FSH greater than 30 IU/L or surgically not sterile), must agree to practice an effective method of avoiding pregnancy (including oral or implanted contraceptives, intrauterine device, condom, diaphragm with spermicidal, cervical cap, abstinence or sterile sex partner) from the time informed consent is signed through follow-up. Males must agree to take appropriate precautions to avoid fathering a child from screening through follow-up.
10. No other active malignancy requiring treatment in the last 3 years other than adequately treated non-melanomatous skin cancer, adequately treated cervical carcinoma in-situ, superficial adequately treated bladder cancer or prostatic intraepithelial neoplasia without evidence of prostate cancer.
11. Adequate bone marrow, liver and renal function as assessed by the following:

    A. Hemoglobin \> or = 8 g/dL B. WBC \> or = 4,000/uL C. Absolute neutrophil count \> or = 1,500/uL D. Platelets \> or = 75,000/uL E. Total bilirubin \< or = 1.5 times ULN F. ALT and AST \< or = 5 times ULN G. Creatinine \< or = 1.5 times ULN H. Albumin \> or = 2.5 mg/dL
12. Subjects who have received previous radiotherapy, loco-regional, or systemic therapy are eligible. A minimum interval of 4 weeks since the last anti-cancer treatment of any kind is required.
13. Subjects with brain metastases or a history of previously treated brain metastasis are eligible but must:

A. Have been treated by surgery or stereotactic radiosurgery (SRS) at least 4 weeks prior to enrollment B. AND have a baseline MRI or CT that shows no evidence of active intercranial disease C. AND be off steroids for at least 1 week prior to study enrollment

Exclusion Criteria:

1. Any concurrent active malignancy requiring treatment (other than basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, superficial bladder tumors, or other malignancies curatively treated \> 3 years prior to study entry)
2. History of severe cardiovascular disease within the last 12 months: symptomatic congestive heart failure, myocardial infarction, coronary artery disease (CAD), life threatening arrhythmias, uncontrolled hypertension
3. Renal failure requiring hemo- or peritoneal dialysis
4. Unstable systemic diseases or active uncontrolled infection
5. Known history of HIV infection
6. Clinically significant gastrointestinal bleeding within 30 days prior to study entry
7. Major surgery, open biopsy or significant traumatic injury within 4 weeks prior to study entry
8. Child's-Pugh Class C
9. Any malabsorption problem that, in the investigator's opinion, would prevent adequate absorption of the study drug
10. Presence of any other medical complications that in the investigator's opinion, suggests a survival of \< 3 months
11. Substance abuse, or medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results
12. Patient inability to swallow oral medications
13. Any condition that is unstable or which could jeopardize the safety of the patient and his/her compliance in the study
14. Pregnant or breast-feeding patients
15. Being of reproductive potential and unable or unwilling to practice an effective contraceptive method
16. Lack of positive staining for RB-function on tumor biopsy.

• Philadelphia, Pennsylvania, United States