Patients with liver cirrhosis and hepatocellular carcinoma will undergo transarterial chemoembolisation (TACE) as clinically indicated and will be randomized to receive bevacizumab or placebo every 2 weeks up to 1 year. Tumor response will be assessed using MR of the liver and PET-scanning. It will be tested whether the addition of bevacizumab as angiogenic inhibitor will slow down tumor progression, reduce the need for re-embolisation and will improve patient survival.
TACE is an established therapy for patients with advanced stage HCC not amenable to liver transplantation or resection and has been shown to significantly improve survival in these patients compared to no treatment (8). TACE takes advantage of the predominantly arterial blood supply of malignant liver tumors contrary to the surrounding normal liver tissue, which receives more blood supply through the portal venous system. TACE leads to predictable tumor necrosis until new blood vessels grow into the tumor margins to support tumor growth. Quite often after cutting off the blood supply through the hepatic artery, the tumor induces active angiogenesis to promote collateral blood vessel growth from liver capsule arteries or collaterals from the gastroduodenal artery. VEGF seems to be an important player in inducing this angiogenetic activity and tumor control and survival of patients after TACE have been linked to serum VEGF-levels with higher levels showing reduced survival. Inhibition of these neoangiogenetic activity could lead to significantly improved in tumor control and survival in patients with advanced stage HCC. 2\. STUDY OBJECTIVE * to assess the effectiveness of bevacizumab in combination with TACE as measured by patients without tumor progression on MRT after 3 cycles of TACE as well as the number of TACE cycles applied for recurrent tumor after a maximum of one year treatment with bevacizumab * to assess collateral tumor vessel growth on MRT / CT
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
32
bevacizumab 5 mg/kg i.v. every 14 days for 52 weeks
Medizinische Universität Wien
Vienna, Austria
to assess the effectiveness of bevacizumab in combination with TACE as measured by patients without tumor progression after a maximum of one year treatment with bevacizumab
Time frame: 12 months
to assess collateral tumor vessel growth on MRT / CT after 3, 6, and 12 months
Time frame: 12 months
overall survival
Time frame: 12 months
time to progression
Time frame: 12 months
safety
Time frame: 12 months
total number of TACE-cycles applied
Time frame: 12 months
metabolically active tumor size on PET-scan
Time frame: 12 months
circulating endothelial progenitors and pro-angiogenic hematopoietic cells as markers of angiogenesis
Time frame: 12 months
HGF-levels during therapy
Time frame: 12 months
portal hypertension and systemic hemodynamics
Time frame: 12 months
cost
Time frame: 12 months
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