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AVATACE-1: Bevacizumab (Avastin®) as Inhibitor of Collateral Tumor Vessel Growth During Transarterial Chemoembolisation (TACE) for Hepatocellular Carcinoma (HCC) a Pilot Trial

Phase 2
18 Years
85 Years
Not Enrolling
Hepatocellular Carcinoma

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Trial Information

AVATACE-1: Bevacizumab (Avastin®) as Inhibitor of Collateral Tumor Vessel Growth During Transarterial Chemoembolisation (TACE) for Hepatocellular Carcinoma (HCC) a Pilot Trial

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

Inhibition of these neoangiogenetic activity could lead to significantly improved in tumor
control and survival in patients with advanced stage HCC.


- 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

- to assess collateral tumor vessel growth on MRT / CT

Inclusion Criteria:

- 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) or patients awaiting OLT with an
expected waiting time >12 months

- Child-Pugh Stage A and 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

- Women of childbearing potential must have a negative serum pregnancy test done 1 week
prior to the administration of the study drug. 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)

- Proteinuria at baseline:

- Urine dipstick of proteinuria <2+. Patients discovered to have >2+ proteinuria
on dipstick urinalysis at baseline, should undergo a 24-hour urine collection
and must demonstrate less <= 1 g of protein/24 hr.

- 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

Exclusion Criteria:

- extra hepatic 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

- 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

- Patients with known allergy to Chinese hamster ovary cell proteins or other
recombinant human or humanized antibodies or to any excipients of Bevacizumab
formulation; or to any other study drugs

- 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 randomisation), myocardial infarction
(≤ 6 months prior to randomisation), 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 an investigational drug or patient at high risk from
treatment complications

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Outcome Measure:

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

Outcome Time Frame:

12 months

Safety Issue:


Principal Investigator

Markus Peck-Radosavljevic, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Medizinische Universität Wien


Austria: Federal Ministry for Health and Women

Study ID:




Start Date:

January 2006

Completion Date:

December 2010

Related Keywords:

  • Hepatocellular Carcinoma
  • hepatocellular carcinoma
  • TACE
  • transarterial chemoembolisation
  • portal hypertension
  • angiogenesis
  • VEGF
  • bevacizumab
  • Carcinoma
  • Carcinoma, Hepatocellular