Micro and Macro Ateriolar Blockade of Hepatocellular Carcinoma (HCC): Treatment With Sorafenib Before and After Hepatic Arterial Embolization (HAE) Therapy for Liver Cancer.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically or cytologically confirmed hepatocellular carcinoma (HCC)
- Single lesion > 6.5 cm; > 3 tumors, any tumor with a diameter > 4.5 cm; or a
cumulative tumor diameter > 8.0 cm
- Stage B (intermediate) disease according to the Barcelona Clinic Liver Cancer
(BCLC) classification system
- Unresectable, multinodular asymptomatic tumor
- No vascular invasion (including segmental portal invasion)
- No extrahepatic spread
- Stage C disease (according to the BCLC classification system) with portal vein
invasion that is limited to a sub-segmental branch of either the right or left
portal vein (i.e., sub-segmental portal vein invasion)
- Being considered for hepatic arterial embolization
- Must have ≥ 1 tumor lesion that can be accurately measured in ≥ 1 dimension according
to RECIST criteria
- The measurable lesion must not have been previously treated with local therapy
(e.g., surgery, radiotherapy, radiofrequency ablation, PEI, or cryoablation)
- Child Pugh class A-B7 liver function
- No diffuse HCC
- No unstable ascites
- No known brain metastasis or CNS disease
- Patients with neurological symptoms must undergo a CT scan/MRI of the brain to
exclude brain metastasis
PATIENT CHARACTERISTICS:
- ECOG performance status 0-1
- Life expectancy ≥ 12 weeks
- ANC ≥ 1,500/mm³
- Platelet count ≥ 75,000/mm³
- Hemoglobin ≥ 9.0 g/dL
- Total bilirubin ≤ 2 mg/dL
- ALT and AST ≤ 2.5 times upper limit of normal (ULN) (≤ 5 times ULN for patients with
liver involvement)
- Creatinine ≤ 1.5 mg/dL
- INR < 1.5 or PT/PTT normal
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for ≥ 3 months after
completion of study treatment
- No cardiac disease, including any of the following:
- NYHA class III-IV congestive heart failure
- Unstable angina (anginal symptoms at rest) or new onset angina (within the past
3 months)
- Myocardial infarction within the past 6 months
- No cardiac ventricular arrhythmias requiring anti-arrhythmic therapy
- No uncontrolled hypertension, defined as systolic BP > 150 mm Hg or diastolic BP > 90
mm Hg, despite optimal medical management
- No known HIV infection
- No active clinically serious infection > CTCAE grade 2, except hepatitis B or C
- No thrombolic or embolic event (e.g., cerebrovascular accident, including transient
ischemic attacks) within the past 6 months
- No pulmonary hemorrhage or bleeding event ≥ CTCAE grade 2 within the past 4 weeks
- No other hemorrhage or bleeding event ≥ CTCAE grade 3 within the past 4 weeks
- No clinically significant gastrointestinal bleeding within the past 30 days
- No serious non-healing wound, ulcer, or bone fracture
- No evidence or history of bleeding diathesis or coagulopathy
- No significant traumatic injury within the past 4 weeks
- No known or suspected allergy to sorafenib tosylate or any agent given in the course
of this study
- No condition that would impair the ability to swallow whole pills
- No malabsorption problem
- No porto-systemic shunt
- No renal failure
- No severe atheromatosis
- No encephalopathy ≥ grade 1
- No contraindication for any of the following:
- Arterial procedure (e.g., impaired clotting tests [e.g., platelet count <
50,000/mm³ or prothrombin activity < 50%])
- Systemic chemotherapy administration (e.g., serum bilirubin > 5 mg/dL, leukocyte
count < 3,000/mm³)
- Sorafenib tosylate administration
- No substance abuse or medical, psychological, or social condition that would
interfere with study participation or evaluation of study results
- No other prior or concurrent cancer, except cervical carcinoma in situ, treated basal
cell carcinoma, superficial bladder tumor (Ta, Tis, or T1), or cancer that was
curatively treated > 3 years ago
PRIOR CONCURRENT THERAPY:
- More than 4 weeks since prior surgery or open biopsy
- No prior systemic chemotherapy or targeted agents
- No concurrent St. John's wort or rifampin
- No concurrent therapy for hepatitis A, B, or C
- Concurrent anti-coagulation with warfarin or heparin allowed