A Phase 1/2 interventional study of Sorafenib and Transarterial chemoembolisation (TACE) in Hepatocellular Carcinoma, sponsored by Medical University of Vienna. Completed at 1 site in Austria. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2010-11-09.
Sponsored by Medical University of Vienna · Phase 1/2, Interventional, and Treatment
Hepatocellular carcinoma (HCC) as the third most common cause of cancer-related death has a very poor prognosis. Aim of this open label single arm non randomized pilot trial is the evaluation of the efficacy and safety of sorafenib in combination with TACE in patients with unresectable HCC. Efficacy ad safety will be compared with a historical TACE-only group of a placebo controlled TACE-trial.
Hepatocellular carcinoma (HCC) as the third most common cause of cancer-related death has a very poor prognosis.
Aim 1: Efficacy of Sorafenib in combination with TACE TACE is an established therapy for patients with unresectable HCC and has been shown to significantly improve survival in these patients compared to no treatment. 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 leading to tumor recovery and proliferation. Inhibition of this neoangiogenetic and proliferation activity after TACE by the multikinase inhibitor Sorafenib, already approved for HCC, could lead to significantly improvement in tumor control and survival in patients with advanced stage HCC.Safety will be compared with a historical TACE-only group of a placebo controlled TACE-trial.
Aim 2: Safety of Sorafenib in combination with TACE:
So far there are no reports about the safety of Sorafenib in combination with TACE. Here we evaluate the safety and tolerability of this combination until 12 weeks after the last TACE.
Aim 3: PPG-Measurement:
Development of portal hypertension in cirrhosis occurs due to two main pathophysiologic mechanisms: the increase in resistance to portal blood flow resulting from increased intrahepatic resistance and the decreased arteriolar vascular tone in the splanchnic vascular bed leading to increased splanchnic inflow of blood. Very recently, it has been shown that increased splanchnic inflow does not only result from arteriolar vasodilation due to excess NO-production in the splanchnic vascular bed but also from an increase in neoangiogenesis in the splanchnic circulation. Increased neovessel formation occurred within a few days of onset of portal hypertension both in a cirrhotic and an extrahepatic murine model of portal hypertension. Neoangiogenesis was effectively inhibited by either an antibody against VEGF-R2 or an inhibitor of VEGF-R2 autophosphorylation, resulting in a reduction of splanchnic blood flow.
Most recently, a combination of a VEGF and a PDGF blocker further decreased portal pressure in an experimental preclinical model.
As Sorafenib is a VEGF and PDGF blocker, we aim to analyze the influence of Sorafenib on portal hypertension and systemic and hepatic hemodynamics.
Aim 4: Biomarkers for treatment response:
Furthermore, we aim to analyze methylated tumor DNA in serum of patients with HCC undergoing Sorafenib treatment and TACE as possible marker of treatment response.
3,249 studies on the registry are indexed under Carcinoma, Hepatocellular; 974 are open to participants now.
This study's planned enrollment of 22 is below the median of 55 across 2,347 interventional studies indexed under Carcinoma, Hepatocellular.
Browse Carcinoma, Hepatocellular studies →Medical University of Vienna is the lead sponsor of 1,105 studies on the registry; 182 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Fertile women and men of childbearing potential ( \< 2 years after last menstruation in women) must use effective means of contraception (oral contraceptives, intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly or surgically sterile)
Absolute neutrophil count (ANC) > 1 x 109/L Platelet count > 40 x 109/L Haemoglobin > 9 g/dL (may be transfused to maintain or exceed this level) Prothrombin time ≥ 40%
Total bilirubin \< 5 mg/dL Serum creatinine \< 3.0 mg/dL
Exclusion Criteria:
all patients will be treated with sorafenib
Drug: Sorafenib · Procedure: Transarterial chemoembolisation (TACE)
All patients will receive Sorafenib (800 mg/day) p.o. beginning two weeks before the first TACE and every day thereafter until patient death or premature withdrawal from study.
Also known as: Nexavar (brand name)
TACE will be carried out with doxorubicin (75 - 50 - 25 mg/m2, depending on serum bilirubin levels ≤ 1.5, 1.5 - 3, 3 - 5 mg/dL) : lipiodol (1:1) in a total volume of 20 mL; after administration of doxorubicin:lipiodol, additional embolisation will be carried out with bead block-endospheres. TACE will be repeated every 4 weeks for 3 cycles; additional cycles will be offered if clinically indicated (but no PEI or RF-ablation should be carried out after inclusion into the study)
Time to Progression (Efficacy)
Time frame: Until disease progression
Safety of Sorafenib in combination with TACE
Time frame: Continuously until 12 weeks after the last TACE
The record gives a start of Sep 2008, a primary completion of Oct 2010 and a completion of Nov 2010. It does not say whether these dates are actual or estimated.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Nov 2010. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Studies of the drug tested here: Sorafenib
Medical University of Vienna →