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Diffuse HCC or presence of vascular invasion or extrahepatic spread or more than 7 lesions or at least one lesion >= 7 cm
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Clinically relevant ascites
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Uncontrolled pleural effusion or pericardial effusion
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History or presence of hepatic encephalopathy
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Co-infection of HBV and HCV
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Patients on a liver transplantation list
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Prior systemic therapy for HCC
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Prior treatment with TACE or selective internal radiation treatment (SIRT)
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Any condition representing a contraindication to TACE
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Major gastrointestinal bleeding within 4 weeks prior to randomization, untreated or incompletely treated varices with bleeding or high-risk for bleeding
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Active or history of autoimmune disease or immune deficiency
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Prior allogeneic stem cell or solid organ transplantation
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History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
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Active tuberculosis
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Severe infection requiring antibiotics within 4 weeks prior to randomization
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Significant cardiovascular disease
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History of congenital long QT syndrome or corrected QT interval >500 ms at screening ECG
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Inadequately controlled arterial hypertension or prior history of hypertensive crisis or hypertensive encephalopathy
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Significant vascular disease including aortic aneurysm requiring surgical repair or peripheral arterial thrombosis with 6 months prior to randomization
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History of abdominal or tracheoesophageal fistula or gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to randomization
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History or clinical signs of gastrointestinal obstruction or requirement for routine parenteral hydration, parenteral nutrition, or tube feeding. Evidence of abdominal free air that is not explained by paracentesis or recent surgical procedure
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History of intra-abdominal inflammatory process within 6 months prior to randomization, including but not limited to peptic ulcer disease, diverticulitis, or colitis
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Evidence of bleeding diathesis or significant coagulopathy
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Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications
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Uncontrolled tumor-related pain. Patients requiring pain medication must be on a stable regimen at enrollment
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Severe, non healing or dehisced wound, active ulcer, or untreated bone fracture
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History of malignancy other than HCC, with the exception of patients who have been disease-free for at least five years before enrollment or patients with adequately treated and completely resected basal cell or squamous cell skin cancer, in situ cervical, breast or prostate cancer, stage I uterine cancer
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Current or recent (within 10 days of randomization) use of acetylsalicyclic acid or treatment with dipyramidole, ticlopidine, clopidogrel, and cilostazol
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Current or recent (within 10 days prior to randomization) use of full dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic purpose
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Chronic daily treatment with a nonsteroidal anti-inflammatory drug (NSAID). Occasional use of NSAIDs for the symptomatic relief of medical conditions such as headache or fever is allowed
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Treatment with a live, attenuated vaccine within 4 weeks prior to randomization, or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the last dose of atezolizumab
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Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and antiPD-L1 therapeutic antibodies
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Hypersensitivity to atezolizumab or bevacizumab or any of the excipients, known hypersensitivity to Chinese hamster ovary cell products, known hypersensitivity to human or humanized antibodies
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Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 [IL-2]) within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to randomization
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Treatment with systemic immunosuppressive medication within 2 weeks prior to randomization, or anticipation of need for systemic immunosuppressive medication during study treatment, with the following exceptions
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Patients who received acute, low-dose systemic immunosuppressant medication or
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a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours
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of corticosteroids for a contrast allergy) are eligible
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Inhaled corticosteroids for chronic obstructive pulmonary disease or bronchial
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asthma, supplemental mineralocorticosteroids or low-dose corticosteroids for
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adrenalcortical insufficiency are allowed
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\. Major surgical procedure other than for diagnosis, open biopsy, or
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significant traumatic injury within 28 days prior to randomization, or
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abdominal surgery, abdominal interventions or significant abdominal traumatic
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injury within 60 days prior to randomization or anticipation of need for major
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surgical procedure during the course of the study or non-recovery from side
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effects of any such procedure
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\. Core biopsy or other minor surgical procedure, excluding placement of a
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vascular access device, within 3 days prior to the first dose of bevacizumab
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\. Pregnant or breastfeeding females
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\. Participation in a clinical trial or experimental drug treatment within
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days prior to inclusion in the clinical trial or within a period of 5 half-
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lives of the substances administered in a clinical trial or during an
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experimental drug treatment prior to inclusion in the clinical trial
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depending on which period is longest, or simultaneous participation in another
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clinical trial while taking part in this clinical trial
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\. Patient committed to an institution by virtue of an order issued either
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by the judicial or the administrative authorities
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\. Patient possibly dependent from the investigator including the spouse
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children and close relatives of any investigator
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