Clinical trial NCT00280007 (phase 2, status: terminated)
Conditions: hepatocellular carcinoma
ICD codes: C22.0, C4A.9, C7B.1, C4A.0, C4A.31, C4A.51, C4A.8
Drugs: bevacizumab
SMILES: [H][N]1([H])[C@@H]2CCCC[C@H]2[N]([H])([H])[Pt]11OC(=O)C(=O)O1
Reason stopped: 
    safety concerns in the treatment arm
  
Eligibility 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 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