A Study of Atezolizumab in Combination With Bevacizumab Compared With Sorafenib in Patients With Untreated Locally Advanced or Metastatic Hepatocellular Carcinoma
Condition: Carcinoma, Hepatocellular
MeSH terms: Carcinoma; Carcinoma, Hepatocellular
Intervention: Atezolizumab; Bevacizumab; Sorafenib
Intervention description: Atezolizumab will be administered by IV, 1200 mg on day 1 of each 21 day cycle; Bevacizumab will be administered by IV, 15 mg/kg on day 1 of each 21 day cycle; Sorafenib will be administered by mouth, 400 mg twice per day, on days 1-21 of each 21-day cycle
Intervention MeSH terms: Bevacizumab; Atezolizumab; Sorafenib
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 558.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This study will evaluate the efficacy and safety of atezolizumab in combination with
      bevacizumab compared with sorafenib in participants with locally advanced or metastatic
      Hepatocellular Carcinoma (HCC) who have received no prior systemic treatment.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Locally advanced or metastatic and/or unresectable Hepatocellular Carcinoma (HCC)

          -  No prior systemic therapy for HCC. Previous use of herbal therapies/traditional
             Chinese medicines with anti-cancer activity included in the label is allowed, provided
             that these medications are discontinued prior to randomization.

          -  At least one measurable untreated lesion

          -  ECOG Performance Status of 0 or 1

          -  Adequate hematologic and end-organ function

          -  For women of childbearing potential: agreement to remain abstinent

          -  For men: agreement to remain abstinent

          -  Child-Pugh class A

        Exclusion Criteria:

          -  History of leptomeningeal disease

          -  Active or history of autoimmune disease or immune deficiency

          -  History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced
             pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening
             chest computed tomography scan

          -  Known active tuberculosis

          -  History of malignancy other than HCC within 5 years prior to screening, with the
             exception of malignancies with a negligible risk of metastasis or death

          -  Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment
             or within at least 5 months after the last dose of atezolizumab, 6 months after the
             last dose of bevacizumab, or 1 month after the last dose of sorafenib

          -  Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC

          -  Untreated or incompletely treated esophageal and/or gastric varices with bleeding or
             high-risk for bleeding

          -  A prior bleeding event due to esophageal and/or gastric varices within 6 months prior
             to initiation of study treatment.

          -  Moderate or severe ascites

          -  History of hepatic encephalopathy

          -  Co-infection of HBV and HCV

          -  Symptomatic, untreated, or actively progressing central nervous system (CNS)
             metastases

          -  Uncontrolled tumor-related pain

          -  Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent
             drainage procedures

          -  Uncontrolled or symptomatic hypercalcemia

          -  Treatment with systemic immunostimulatory agents

          -  Inadequately controlled arterial hypertension

          -  Prior history of hypertensive crisis or hypertensive encephalopathy

          -  Evidence of bleeding diathesis or significant coagulopathy

          -  History of intestinal obstruction and/or clinical signs or symptoms of GI obstruction
             including sub-occlusive disease related to the underlying disease or requirement for
             routine parenteral hydration

          -  Serious, non-healing or dehiscing wound, active ulcer, or untreated bone fracture

          -  Metastatic disease that involves major airways or blood vessels, or centrally located
             mediastinal tumor masses

          -  Local therapy to liver within 28 days prior to initiation of study treatment or
             non-recovery from side effects of any such procedure

          -  Chronic daily treatment with a non-steroidal anti-inflammatory drug (NSAID)