Sorafenib Tosylate and Chemoembolization in Treating Patients With Unresectable Liver Cancer

PRIMARY OBJECTIVE:

I. To evaluate the toxicity and safety of integrating sorafenib with chemoembolization for unresectable hepatocellular carcinoma.

SECONDARY OBJECTIVE:

I. To observe the imaging response (AASLD/EASL modification of RECIST) and time to progression following chemoembolization in conjunction with sorafenib.

OUTLINE:

Patients receive oral sorafenib tosylate twice daily. Beginning 2 weeks later, patients undergo chemoembolization with cisplatin, doxorubicin hydrochloride, and mitomycin C.

Chemoembolizaton repeats once a month for up to 4 procedures in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed at 4 weeks and then every 3 months.

Inclusion

• Histologically confirmed hepatocellular carcinoma
• AND/OR Magnetic Resonance Imaging (MRI) or Computerized Tomography (CT) consistent with liver cirrhosis AND at least one solid liver lesion > 2cm with arterial-phase enhancement and delayed washout regardless of alpha-feto protein levels (AFP)
• AND/OR AFP > 400ng/mL AND evidence of at least one solid liver lesion > 2cm regardless of specific imaging characteristics on CT or MRI
• Patient is not a candidate for transplantation, resection, or ablation; for whom the intended therapy is chemoembolization
• Patient meets clinical criteria for treatment with chemoembolization
• Absolute contraindications to chemoembolization include an uncorrectable bleeding disorder, uncorrectable contrast sensitivity, leukopenia (white blood cell count < 1000/uL), cardiac or renal insufficiency (serum creatinine > 2.0mg/dL), hepatic encephalopathy, jaundice, or dilated intrahepatic bile ducts
• Portal vein occlusion is a relative contraindication and chemoembolization can be performed only if there are collateral vessels with hepato-pedal flow demonstrated angiographically
• Hepatic compromise as determined by the following combination of parameters is a contraindication to therapy: lactate dehydrogenase > 425 U/L, aspartate aminotransferase > 100 U/L, total bilirubin > 2.0 mg/dL and > 50% liver volume replaced by tumor
• Patients may have been treated with ablation or resection in the past, but no sooner than 4 weeks before study registration
• Patients may NOT have been previously treated with sorafenib, chemoembolization, radioembolization, or systemic chemotherapy with cytotoxic agents or molecularly targeted agents
• ECOG performance status =< 2
• Life expectancy of greater than 3 months
• Platelets >= 50,000/mcL
• Total bilirubin =< 2.0 mg/dl
• AST(SGOT)/ALT(SGPT) =< 3X institutional upper limit of normal
• Creatinine =< 1.5 mg/dl
• INR =< 1.5
• Patients must have no clinical signs of heart failure and meet New York Heart Association functional classification I or II defined as:

Class I - Patients with no limitation of activities; they suffer no symptoms from ordinary activities; Class II - Patients with slight, mild limitation of activity; they are comfortable with rest or with mild exertion

• Because agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation
• Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
• Ability to understand and the willingness to sign a written informed consent document

Exclusion

• Patients may not be receiving any other investigational agents
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to sorafenib
• History of radiologic contrast reactions not controlled by standard premedications
• Patients must not be taking cytochrome P450 enzyme inducing drugs
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, uncontrolled hypertension, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women are excluded from this study
• Breastfeeding should be discontinued
• Prophylactic use of G-CSF or GM-CSF is not permitted on this trial