• To determine the MTD, dose limiting toxicities and overall safety profile of DENSPM intravenous infusion in patients with unresectable HCC.
  

• To evaluate antitumor response as measured by progression free survival when DENSPM is administered for up to eight 28 day cycles in patients with advanced HCC.
  
• To evaluate the pharmacokinetics of DENSPM in plasma and HCC tissue in patients unresectable HCC.
  

Inclusion Criteria:

• Histologically proven HCC, or if the patient is not a medically appropriate candidate for biopsy, then all of the following criteria must be met: A.History of cirrhosis or chronic hepatitis B virus (HBV) or hepatitis C virus (HCV)infection. B.A focal liver lesion ≥ 3 cm on CT or MRI with arterial hypervascularization. C.Confirmation of the liver lesion by a second imaging modality (US/ CT/ MRI).D.AFP ≥1000 ng/ml, or ≥ 4000 ng/ml if Hepatitis B surface Ag positive.
• For recurrent HCC, radiographic evidence of progression.
• Not appropriate for curative therapy (surgical resection) or refuses potentially curative therapy
• Measurable disease, defined as having at least one measurable intrahepatic tumor lesion (using Response Criteria in Solid Tumors [RECIST]). Prior therapy is acceptable only if there is documented progression of the selected measurable lesion(s) following completion of the therapy.
• Required laboratory values
• Renal function: serum creatinine ≤1.2mg/dL Hematologic function: leukocyte count ≥1,500/mm3, platelet count ≥50,000/mm3 Hepatic function: transaminases ≤5x upper limit normal (ULN), albumin ≥2.0g/dL, total bilirubin ≤3.5mg/dL Sodium: ≥130mEq/L
• Karnofsky Performance Status of ≥ 60%
• CLIP Score ≤ 3
• If female and of childbearing potential, must use an effective method of contraception
• Willing and able to provide written informed consent

Exclusion Criteria:

• Has received localized therapy (e.g., radiotherapy, RFA, injection therapy, or chemoembolization)within 6 weeks prior to treatment, Day1. Prior local lesion-specific radiotherapy is acceptable only if the treated lesion(s) is/are not the only source of measurable disease or there is documented progression of the treated lesion(s) following completion of the therapy.
• Has received any other systemic therapy for HCC within 3 weeks prior to treatment, Day 1. Prior therapy is acceptable only if there is documented progression following completion of the therapy.
• Has received another investigational therapy within 30 days prior to study entry
• Has any unstable serious or life-threatening medical condition, other than HCC (e.g., unstable angina, other cancer diagnosis with the exception of basal cell carcinoma, or patients with prior malignancy except for adequately treated basal cell carcinoma(s), in situ cervical cancer, or other cancer for which the patient has been disease-free for five or more years)
• Newly noted clinically significant electrocardiogram (ECG) abnormality
• Clinically significant abnormal laboratory result that is not consistent with patient's clinical course
• Active gastrointestinal bleeding resulting in clinically significant hemodynamic changes or a reduction in hemoglobin.
• Active inflammatory bowel disease (IBD) and/or active gastric or duodenal ulcer disease
• Has a history of central nervous system (CNS) metastases, seizure disorder or neurological exam finding suggestive of CNS metastases
• Has Stage B or C liver cirrhosis according to Child-Pugh-Turcotte Classification
• Has ascites refractory to diuretic therapy
• Has any contraindication for MRI procedure
• If female of childbearing potential, has a positive serum HCG
• If female, is lactating