Hepatocellular CarcinomaPhase 1/2NCT00768937
Sorafenib and Transarterial Chemoembolization for Hepatocellular Carcinoma
A Phase 1/2 study testing Sorafenib and Transarterial chemoembolisation (TACE) in people with Hepatocellular Carcinoma, run by Medical University of Vienna at 1 site in Austria.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatocellular Carcinoma
- What is being tested?
- Sorafenib and Transarterial chemoembolisation (TACE)
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteAustria
- Study dates
- Sep 2008to Nov 2010
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with histologically confirmed HCC not suitable for OLT or resection ( > 3 nodules, >5 cm diameter, vascular invasion, clinically significant portal hypertension, other contraindications against OLT)
- Child-Pugh Stage A or B
- Liver disease of any etiology
- Written informed consent (approved by the Institutional Review Board [IRB]/Independent Ethics Committee [IEC]) obtained prior to any study specific screening procedures
- Patient must be able to comply with the protocol
- Age ≥ 18 years
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- Women of childbearing potential must have a negative serum pregnancy test done 1 week prior to the administration of the Sorafenib.
- 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)
- Haematology:
- 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%
- Biochemistry:
- Total bilirubin < 5 mg/dL Serum creatinine < 3.0 mg/dL
- Life expectancy of > 3 months
Who cannot join
- Extrahepatic tumor spread
- Complete portal vein thrombosis (common trunk)
- Child-Pugh-Stage C
- Prior TACE or TAE
- Other experimental therapies for HCC
- Acute variceal bleeding within the last 2 weeks
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- Large oesophageal varices ( > 5 mm diameter) without prophylactic band ligation
- Past or current history (within the last 2 years prior to randomisation) of malignancies except for the indication under this study and curatively treated basal and squamous cell carcinoma of the skin or in situ carcinoma of the cervix
- History or evidence upon physical examination of CNS disease unless adequately treated (e.g., seizure not controlled with standard medical therapy or history of stroke within < 6 months), excluding hepatic encephalopathy
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study treatment start, or anticipation of the need for major surgical procedure during the course of the study
- Current or recent (within 10 days prior to study treatment start) use of full-dose oral or parenteral anticoagulants for therapeutic purposes
- Chronic, daily treatment with aspirin (>325mg/day)
- Pregnancy (positive serum pregnancy test) or lactation
- Uncontrolled hypertension
- Serious, non-healing wound, ulcer, or bone fracture
- Currently or recent (within the 30 days prior to starting study treatment) treatment of another investigational drug or participation in another investigational study
- Clinically significant (i.e. active) cardiovascular disease for example cerebrovascular accidents ( ≤ 6 months prior to study entry), myocardial infarction ( ≤ 6 months prior to study entry), unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication
- Evidence of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of Sorafenib/TACE or patient at high risk from treatment complications
Trial locations and contacts
1 site in 1 country.
Austria1 site
Abteilung Gastroenterologie und Hepatologie, Medizinische Universität und AKH Wien
Vienna, 1090
About this study
Official title: Sorafenib as Inhibitor of Collateral Tumor Vessel Growth During Transarterial Chemoembolisation (TACE) for Hepatocellular Carcinoma (HCC)- a Pilot Trial to Evaluate Safety and Biological Response
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.
Read the detailed description
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.
- Conditions
- Hepatocellular Carcinoma
- Being tested
- Sorafenib, Transarterial chemoembolisation (TACE)
- Keywords
- hepatocellular carcinoma, sorafenib, transarterial chemoembolization, tumor angiogenesis, angiogenic factors
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SorafenibDrug
Also called Nexavar (brand name)
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.
Transarterial chemoembolisation (TACE)Procedure or surgery
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)
| Study group | Role | What they receive |
|---|---|---|
| Treatment arm | Experimental | all patients will be treated with sorafenib Receives: Drug: Sorafenib; Procedure: Transarterial chemoembolisation (TACE) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to Progression (Efficacy)
Measured: Until disease progression
Safety of Sorafenib in combination with TACE
Measured: Continuously until 12 weeks after the last TACE
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Oct 2008 (estimated)
- Study startSep 2008
- Primary completionOct 2010
- Study completionNov 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- More trials run by Medical University of ViennaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 22 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Medical University of Vienna
- Sponsor type
- University, hospital or other
- Investigators
- Markus Peck-Radosavljevic, Prof. Dr., Principal investigator, Abteilung Gastroenterologie und Hepatologie, Medizinische Universität und AKH Wien
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00768937
- Sponsor's protocol ID
- SORATACE1
- Status last verified
- Nov 2010
- First submitted
- 3 Oct 2008
- Last updated
- 9 Nov 2010
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Nov 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sorafenib as Inhibitor of Collateral Tumor Vessel Growth During Transarterial Chemoembolisation (TACE) for Hepatocellular Carcinoma (HCC)- a Pilot Trial to Evaluate Safety and Biological Response
- ClinicalTrials.gov ID
- NCT00768937
- Acronym / sponsor ID
- SORATACE1
- Conditions
- Hepatocellular Carcinoma
- Keywords
- hepatocellular carcinoma, sorafenib, transarterial chemoembolization, tumor angiogenesis, angiogenic factors
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (estimated)
- Lead sponsor
- Medical University of ViennaUniversity, hospital or other
- Study start
- Sep 2008
- Primary completion
- Oct 2010 (actual)
- Study completion
- Nov 2010 (actual)
- First posted
- 8 Oct 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment arm | Experimental | Drug: Sorafenib, Procedure: Transarterial chemoembolisation (TACE)all patients will be treated with sorafenib |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Patients with histologically confirmed HCC not suitable for OLT or resection ( > 3 nodules, >5 cm diameter, vascular invasion, clinically significant portal hypertension, other contraindications against OLT)
- Child-Pugh Stage A or B
- Liver disease of any etiology
- Written informed consent (approved by the Institutional Review Board [IRB]/Independent Ethics Committee [IEC]) obtained prior to any study specific screening procedures
- Patient must be able to comply with the protocol
Key exclusion criteria (18 listed)
- Extrahepatic tumor spread
- Complete portal vein thrombosis (common trunk)
- Child-Pugh-Stage C
- Prior TACE or TAE
- Other experimental therapies for HCC
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SorafenibAlso: Nexavar (brand name)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. | Drug | Treatment arm |
| Transarterial chemoembolisation (TACE)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) | Procedure or surgery | Treatment arm |
Primary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Nov 2010.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Markus Peck-Radosavljevic, Prof. Dr. principal investigator
Abteilung Gastroenterologie und Hepatologie, Medizinische Universität und AKH Wien
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Sorafenib and Transarterial chemoembolisation (TACE) in people with Hepatocellular Carcinoma, run by Medical University of Vienna at 1 site in Austria.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Nov 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Austria. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to Progression (Efficacy) (time frame: Until disease progression). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Nov 2010.