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Transarterial Chemoembolisation Plus Bevacizumab for Treatment of Hepatocellular Carcinoma
This study is currently recruiting participants.
Verified by Medical University of Vienna, January 2006
Sponsored by: Medical University of Vienna
Information provided by: Medical University of Vienna
ClinicalTrials.gov Identifier: NCT00280007
  Purpose

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 reembolisation and will improve patient survival.


Condition Intervention Phase
Hepatocellular Carcinoma
Drug: bevacizumab
Phase II

MedlinePlus related topics: Cancer High Blood Pressure
Drug Information available for: Bevacizumab Chlorotrianisene
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title: AVATACE-1: Bevacizumab (Avastin®) as Inhibitor of Collateral Tumor Vessel Growth During Transarterial Chemoembolisation (TACE) for Hepatocellular Carcinoma (HCC) a Pilot Trial

Further study details as provided by Medical University of Vienna:

Primary Outcome Measures:
  • 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
  • to assess collateral tumor vessel growth on MRT / CT after 3, 6, and 12 months

Secondary Outcome Measures:
  • at 12 months:
  • overall survival
  • time to progression
  • safety
  • total number of TACE-cycles applied
  • metabolically active tumor size on PET-scan
  • circulating endothelial progenitors and pro-angiogenic hematopoietic cells as markers of angiogenesis
  • HGF-levels during therapy
  • portal hypertension and systemic hemodynamics
  • cost

Estimated Enrollment: 40
Study Start Date: January 2006
Detailed Description:

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
  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 Committe [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 £ 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 ³ 40%
  • Biochemistry:

    • Total bilirubin £ 5 mg/dL
    • Serum creatinine < 3.0 mg/dL
    • Life expectancy of >3 months

Exclusion Criteria:

  • 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
  • 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 cerebravascular 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00280007

Contacts
Contact: Markus Peck-Radosavljevic, M.D. +43 1 40400 ext 6589 markus.peck@meduniwien.ac.at
Contact: Gregor Ulbrich, M.D. +43 1 40400 ext 6589 gregor.ulbrich@meduniwien.ac.at

Locations
Austria
Medizinische Universität Wien Recruiting
Vienna, Austria, A-1090
Principal Investigator: Markus Peck-Radosavljevic, M.D.            
Sub-Investigator: Gregor Ulbrich, M.D.            
Sponsors and Collaborators
Medical University of Vienna
Investigators
Principal Investigator: Markus Peck-Radosavljevic, M.D. Medizinische Universität Wien
  More Information

Study ID Numbers: MPR-2
Study First Received: January 19, 2006
Last Updated: September 7, 2006
ClinicalTrials.gov Identifier: NCT00280007  
Health Authority: Austria: Federal Ministry for Health and Women

Keywords provided by Medical University of Vienna:
hepatocellular carcinoma
TACE
transarterial chemoembolisation
portal hypertension
angiogenesis
VEGF
bevacizumab

Study placed in the following topic categories:
Liver Diseases
Digestive System Neoplasms
Carcinoma, Hepatocellular
Liver neoplasms
Bevacizumab
Hypertension, Portal
Portal hypertension
Carcinoma
Liver Neoplasms
Digestive System Diseases
Gastrointestinal Neoplasms
Adenocarcinoma
Hypertension
Neoplasms, Glandular and Epithelial
Hepatocellular carcinoma

Additional relevant MeSH terms:
Neoplasms
Neoplasms by Site
Neoplasms by Histologic Type
Antineoplastic Agents
Therapeutic Uses
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Angiogenesis Modulating Agents
Angiogenesis Inhibitors
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 15, 2009