Bevacizumab (Avastin®) as inhibitor of collateral tumor vessel growth during transarterial chemoembolisation (TACE) for Hepatocellular Carcinoma (HCC): a pilot trial - AVATACE-1

• Conditions: Hepatocellular Carcinoma

• Registration Number: EUCTR2004-004963-32-AT
• Lead Sponsor: niv. Prof. Dr. Markus Peck-Radosavljevic

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2005-06-13
• Last Update Posted: 29 April 2013

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 40

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)
?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 ? 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

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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 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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: to assess the effectiveness of bevacizumab in combination with TACE as measured by patients without tumor progression on MRT after 3 TACE-cycles as well as the number of TACE-cycles applied for recurrent tumor after a maximum of one year treatment and to assess collateral tumor vessel growth on MRT / CT.<br><br>;Secondary Objective: overall survival, time to progression, safety, total number of TACE-cyles 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;Primary end point(s): the effectiveness of bevacizumab in combination with TACE as measured by patients without tumor progression on MRT after 3 TACE-cycles as well as the number of TACE-cycles applied for recurrent tumor after a maximum of one year treatment and the collateral tumor vessel growth on MRT / CT<br><br><br>