A Phase III, Open-Label, Randomized Study of Atezolizumab in Combination With Bevacizumab Compared With Sorafenib in Patients With Untreated Locally Advanced or Metastatic Hepatocellular Carcinoma

ClinicalTrials.gov processed this data on October 5, 2023. Link to the current ClinicalTrials.gov record.

Recruitment Status

COMPLETED - HAS RESULTS
 (See Contacts and Locations)
Verified September 2023 by Hoffmann-La Roche

Sponsor

Hoffmann-La Roche

Information Provided by (Responsible Party)

Hoffmann-La Roche

Clinicaltrials.gov Identifier

NCT03434379
Other Study ID Numbers: YO40245
First Submitted: January 31, 2018
First Posted: February 15, 2018
Results First Posted: November 5, 2021
Last Update Posted: October 23, 2023
Last Verified: September 2023
History of Changes

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Study Description

The participants will be randomized in a 2:1 ratio to one of the two treatment arms: Arm A (experimental arm): Atezolizumab +bevacizumab; Arm B (control arm): Sorafenib
Condition or Disease Intervention/Treatment
  • Carcinoma, Hepatocellular
  • Drug: Atezolizumab
  • Drug: Bevacizumab
  • Drug: Sorafenib

Study Design

Study TypeInterventional
Actual Enrollment558 participants
Design AllocationRandomized
Interventional ModelParallel Assignment
MaskingNone (Open Label)
Primary PurposeTreatment
Official TitleA Phase III, Open-Label, Randomized Study of Atezolizumab in Combination With Bevacizumab Compared With Sorafenib in Patients With Untreated Locally Advanced or Metastatic Hepatocellular Carcinoma
Study Start DateMarch 15, 2018
Actual Primary Completion DateAugust 31, 2020
Actual Study Completion DateNovember 17, 2022

Groups and Cohorts

Group/ CohortIntervention/ Treatment
  • Atezolizumab + Bevacizumab
    • Participants will receive Atezolizumab + Bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator
  • Drug: Atezolizumab
    • Atezolizumab will be administered by IV, 1200 mg on day 1 of each 21 day cycle
  • Drug: Bevacizumab
    • Sorafenib
      • Participants will receive Sorafenib until unacceptable toxicity or loss of clinical benefit as determined by the investigator
    • Drug: Sorafenib

      Outcome Measures

      Primary Outcome Measures

      1. Overall Survival (OS) in the Global Population [From randomization to death from any cause up to the clinical cut off date (CCOD) of 29Aug2019 (up to approximately 18 months) and 31Aug2020 (up to approximately 30 months)]
        OS was defined as the time from randomization to death from any cause.
      2. Progression Free Survival by Independent Review Facility-Assessment (PFS-IRF) Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 in the Global Population [Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months)]
        PFS was defined as the time from randomization to the first occurrence of progressive disease (PD) or death from any cause whichever occurs first as determined by an IRF according to RECIST v1.1. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of >/= 5 millimeters (mm).
      3. Overall Survival (OS) in the China Population [From randomization to death from any cause up to the clinical cut off date (CCOD) of 29Aug2019 (up to approximately 18 months) and 31Aug2020 (up to approximately 30 months)]
        OS was defined as the time from randomization to death from any cause.
      4. PFS-IRF Per RECIST v1.1 in the China Population [Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months)]
        PFS was defined as the time from randomization to the first occurrence of progressive disease (PD) or death from any cause whichever occurs first as determined by an IRF according to RECIST v1.1. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of >/= 5 millimeters (mm).

      Secondary Outcome Measures

      1. Objective Response Rate by IRF-Assessment (ORR-IRF) Per RECIST v1.1 in the Global Population [Randomization up to CCOD of 29Aug2019 (up to approximately 18 months)]
        ORR was defined as the percentage of participants with a complete response (CR) or a partial response (PR) as determined by the IRF according to RECIST v1.1. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. OR=CR+PR
      2. Objective Response Rate by IRF-Assessment (ORR-IRF) Per Hepatocellular Carcinoma (HCC) Modified RECIST (mRECIST) in the Global Population [Randomization up to CCOD of 29Aug2019 (up to approximately 18 months)]
        ORR was defined as the percentage of participants with CR or PR as determined by the IRF according to HCC mRECIST. HCC mRECIST differentiates between vital tumor and necrotic areas in the liver measuring only the residual vital tumor mass in the liver. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. OR=CR+PR
      3. ORR by Investigator-Assessment (ORR-INV) Per RECIST v1.1 in the Global Population [Randomization up to CCOD of 29Aug2019 (up to approximately 18 months)]
        ORR was defined as the percentage of participants with CR or PR as determined by the investigator according to RECIST v1.1. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. OR=CR+PR
      4. Duration of Response by IRF-Assessment (DOR-IRF) Per RECIST v1.1 in the Global Population [Randomization up to CCOD of 29Aug2019 (up to approximately 18 months)]
        DOR was defined as the time interval from the date of first occurrence of a documented objective response (CR or PR, whichever status is recorded first) until the first date that disease progression (PD) or death was documented, whichever occurs first as determined by the IRF according to RECIST v1.1. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of >/= 5 mm.
      5. Duration of Response by IRF Assessment (DOR-IRF) Per HCC mRECIST in the Global Population [Randomization up to CCOD of 29Aug2019 (up to approximately 18 months)]
        DOR was defined as the time interval from the date of first occurrence of a documented objective response (CR or PR, whichever status is recorded first) until the first date that disease progression (PD) or death was documented, whichever occurs first as determined by the IRF according to HCC mRECIST. HCC mRECIST differentiates between vital tumor and necrotic areas in the liver, measuring only the residual vital tumor mass in the liver CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of >/= 5 mm.
      6. Duration of Response by Investigator Assessment (DOR-INV) Per RECIST v1.1 in the Global Population [Randomization up to CCOD of 29Aug2019 (up to approximately 18 months)]
        DOR was defined as the time interval from the date of first occurrence of a documented objective response (CR or PR, whichever status is recorded first) until the first date that disease progression (PD) or death was documented, whichever occurs first as determined by the investigator according to RECIST v1.1. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of >/= 5 mm.
      7. PFS-IRF Per HCC mRECIST in the Global Population [Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months)]
        PFS was defined as the time from randomization to the first occurrence of progressive disease or death from any cause whichever occurs first as determined by the IRF according to HCC mRECIST. HCC mRECIST differentiates between vital tumor and necrotic areas in the liver, measuring only the residual vital tumor mass in the liver. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of >/= 5 millimeters (mm).
      8. PFS by Investigator Assessment (PFS-INV) Per RECIST v1.1 in the Global Population [Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months)]
        PFS was defined as the time from randomization to the first occurrence of progressive disease or death from any cause whichever occurs first as determined by the investigator according to RECIST v1.1. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of >/= 5 millimeters (mm).
      9. Time to Progression (TTP) by IRF Assessment (TTP-IRF) Per RECIST v1.1 in the Global Population [Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months)]
        Time to progression was defined as the time from the date of randomization to the date of the first documented tumor progression as determined by the IRF according to RECIST v1.1. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of >/= 5 millimeters (mm).
      10. TTP-IRF Per HCC mRECIST in the Global Population [Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months)]
        Time to progression was defined as the time from the date of randomization to the date of the first documented tumor progression as determined by the IRF according to HCC mRECIST. HCC mRECIST differentiates between vital tumor and necrotic areas in the liver, measuring only the residual vital tumor mass in the liver. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of >/= 5 millimeters (mm).
      11. TTP by Investigator Assessment (TTP-INV) Per RECIST v1.1 in the Global Population [Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months)]
        Time to progression was defined as the time from the date of randomization to the date of the first documented tumor progression as determined by the investigator according to RECIST v1.1. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of >/= 5 millimeters (mm).
      12. Overall Survival by Baseline AFP in the Global Population [From randomization to death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months)]
        OS was defined as the time from randomization to death from any cause. Subpopulations with baseline AFP <400 ng/mL and AFP>/= 400 ng/mL were analyzed.
      13. PFS-IRF Per RECIST v1.1 by Baseline AFP in the Global Population [Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months)]
        PFS was defined as the time from randomization to the first occurrence of progressive disease or death from any cause whichever occurs first as determined by the IRF according to RECIST v1.1. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of >/= 5 millimeters (mm). Subpopulations with baseline AFP <400 ng/mL and AFP>/= 400 ng/mL were analyzed.
      14. PFS-INV Per RECIST v1.1 by Baseline AFP in the Global Population [Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months)]
        PFS was defined as the time from randomization to the first occurrence of progressive disease or death from any cause whichever occurs first as determined by the investigator according to RECIST v1.1. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of >/= 5 millimeters (mm). Subpopulations with baseline AFP <400 ng/mL and AFP>/= 400 ng/mL were analyzed.
      15. Time to Deterioration (TTD) in the Global Population [Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months)]
        TTD was defined as the time from randomization to the first deterioration (decrease from baseline of >/= 10 points) in the patient-reported health-related global health status/quality of life (GHS /HRQoL), physical function or role function scales of the European Organization for Research and Treatment of Cancer quality-of-life questionnaire for cancer (EORTC) QLQ-C30, maintained for two consecutive assessments, or one assessment followed by death from any cause within 3 weeks.
      16. Number of Participants With Adverse Events (AEs) in the Global Population [Up to end of study (up to approximately 56 months)]
        An adverse event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
      17. Maximum Serum Concentration (Cmax) of Atezolizumab at Cycle 1 in the Global Population [Post-dose on Day 1 of Cycle 1 (cycle length = 21 days)]
      18. Trough Serum Concentration (Cmin) of Atezolizumab in the Global Population [Pre-dose on Day 1 of Cycles 2, 3, 4, 8, 12 and 16 (cycle length = 21 days)]
      19. Percentage of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab in the Global Population [Baseline and post-baseline on Day 1 (pre-dose) of Cycles 2, 3, 4, 8, 12, 16 (cycle length = 21 days) and treatment discontinuation visit (up to approximately 30 months)]
      20. Objective Response Rate by IRF-Assessment (ORR-IRF) Per RECIST v1.1 in the China Population [Randomization up to CCOD of 29Aug2019 (up to approximately 18 months)]
        ORR was defined as the percentage of participants with a complete response (CR) or a partial response (PR) as determined by the IRF according to RECIST v1.1. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. OR=CR+PR
      21. Objective Response Rate by IRF-Assessment (ORR-IRF) Per Hepatocellular Carcinoma (HCC) Modified RECIST (mRECIST) in the China Population [Randomization up to CCOD of 29Aug2019 (up to approximately 18 months)]
        ORR was defined as the percentage of participants with CR or PR as determined by the IRF according to HCC mRECIST. HCC mRECIST differentiates between vital tumor and necrotic areas in the liver measuring only the residual vital tumor mass in the liver. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. OR=CR+PR
      22. ORR by Investigator-Assessment (ORR-INV) Per RECIST v1.1 in the China Population [Randomization up to CCOD of 29Aug2019 (up to approximately 18 months)]
        ORR was defined as the percentage of participants with CR or PR as determined by the investigator according to RECIST v1.1. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. OR=CR+PR
      23. Duration of Response by IRF-Assessment (DOR-IRF) Per RECIST v1.1 in the China Population [Randomization up to CCOD of 29Aug2019 (up to approximately 18 months)]
        DOR was defined as the time interval from the date of first occurrence of a documented objective response (CR or PR, whichever status is recorded first) until the first date that disease progression (PD) or death was documented, whichever occurs first as determined by the IRF according to RECIST v1.1. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of >/= 5 mm.
      24. Duration of Response by IRF Assessment (DOR-IRF) Per HCC mRECIST in the China Population [Randomization up to CCOD of 29Aug2019 (up to approximately 18 months)]
        DOR was defined as the time interval from the date of first occurrence of a documented objective response (CR or PR, whichever status is recorded first) until the first date that disease progression (PD) or death was documented, whichever occurs first as determined by the IRF according to HCC mRECIST. HCC mRECIST differentiates between vital tumor and necrotic areas in the liver, measuring only the residual vital tumor mass in the liver CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of >/= 5 mm.
      25. Duration of Response by Investigator Assessment (DOR-INV) Per RECIST v1.1 in the China Population [Randomization up to CCOD of 29Aug2019 (up to approximately 18 months)]
        DOR was defined as the time interval from the date of first occurrence of a documented objective response (CR or PR, whichever status is recorded first) until the first date that disease progression (PD) or death was documented, whichever occurs first as determined by the investigator according to RECIST v1.1. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of >/= 5 mm.
      26. PFS-IRF Per HCC mRECIST in the China Population [Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months)]
        PFS was defined as the time from randomization to the first occurrence of progressive disease or death from any cause whichever occurs first as determined by the IRF according to HCC mRECIST. HCC mRECIST differentiates between vital tumor and necrotic areas in the liver, measuring only the residual vital tumor mass in the liver. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of >/= 5 millimeters (mm).
      27. PFS by Investigator Assessment (PFS-INV) Per RECIST v1.1 in the China Population [Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months)]
        PFS was defined as the time from randomization to the first occurrence of progressive disease or death from any cause whichever occurs first as determined by the investigator according to RECIST v1.1. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of >/= 5 millimeters (mm).
      28. Time to Progression (TTP) by IRF Assessment (TTP-IRF) Per RECIST v1.1 in the China Population [Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months)]
        Time to progression was defined as the time from the date of randomization to the date of the first documented tumor progression as determined by the IRF according to RECIST v1.1. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of >/= 5 millimeters (mm).
      29. TTP-IRF Per HCC mRECIST in the China Population [Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months)]
        Time to progression was defined as the time from the date of randomization to the date of the first documented tumor progression as determined by the IRF according to HCC mRECIST. HCC mRECIST differentiates between vital tumor and necrotic areas in the liver, measuring only the residual vital tumor mass in the liver. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of >/= 5 millimeters (mm).
      30. TTP by Investigator Assessment (TTP-INV) Per RECIST v1.1 in the China Population [Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months)]
        Time to progression was defined as the time from the date of randomization to the date of the first documented tumor progression as determined by the investigator according to RECIST v1.1. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of >/= 5 millimeters (mm).
      31. Time to Deterioration (TTD) in the China Population [Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months)]
        TTD was defined as the time from randomization to the first deterioration (decrease from baseline of >/= 10 points) in the patient-reported health-related global health status/quality of life (GHS /HRQoL), physical function or role function scales of the European Organization for Research and Treatment of Cancer quality-of-life questionnaire for cancer (EORTC) QLQ-C30, maintained for two consecutive assessments, or one assessment followed by death from any cause within 3 weeks.
      32. Number of Participants With Adverse Events (AEs) in the China Population [Up to end of study (up to approximately 56 months)]
        An adverse event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
      33. Maximum Serum Concentration (Cmax) of Atezolizumab in the China Population [Post-dose on Day 1 of Cycle 1 (cycle length = 21 days)]
      34. Trough Serum Concentration (Cmin) of Atezolizumab in the China Population [Pre-dose on Day 1 of Cycles 2, 3, 4, 8, 12 and 16 (cycle length = 21 days)]
      35. Percentage of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab in the China Population [Baseline and post-baseline on Day 1 (pre-dose) of Cycles 2, 3, 4, 8, 12, 16 (cycle length = 21 days) and treatment discontinuation visit (up to approximately 18 months)]

      Eligibility Criteria

      Ages Eligible for Study 18 Years and Older (Adult, Older Adult)
      Sexes Eligible for Study All
      Accepts Healthy Volunteers No
      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)

      Contacts and Locations

      Sponsors and Collaborators Hoffmann-La Roche
      Locations
      • St. Josephs Hospital and Medical Center | Phoenix, Arizona, United States, 85260
      • City of Hope | Duarte, California, United States, 91010
      • Uni of California - San Diego; Cancer Center & Dept of Medicine | La Jolla, California, United States, 92093
      • Kaiser Permanente Northern California | Novato, California, United States, 94589
      • University of California Irvine Medical Center | Orange, California, United States, 92868
      • Kaiser Permanente Sacramento Medical Center | Sacramento, California, United States, 95825
      • California Pacific Medical Center | San Francisco, California, United States, 94115
      • Kaiser Permanente - San Francisco Medical Center | San Francisco, California, United States, 94118
      • University of California Los Angeles | Santa Monica, California, United States, 90404
      • Kaiser Permanente - Walnut Creek | Walnut Creek, California, United States, 94596
      • Banner MD Anderson Cancer Center | Greeley, Colorado, United States, 85234
      • Georgetown University | Washington, District of Columbia, United States, 20007
      • Moffitt Cancer Center | Tampa, Florida, United States, 33612
      • Massachusetts General Hospital | Boston, Massachusetts, United States, 02114
      • Henry Ford Health System | Detroit, Michigan, United States, 48202
      • Washington University; Wash Uni. Sch. Of Med | Saint Louis, Missouri, United States, 63110
      • University of New Mexico Comprehensive Cancer Center | Albuquerque, New Mexico, United States, 87102
      • Laura and ISAAC Perlmutter Cancer Center at NYU Langone. | New York, New York, United States, 10016
      • Thomas Jefferson University | Philadelphia, Pennsylvania, United States, 19107
      • M.D Anderson Cancer Center; Uni of Texas At Houston | Houston, Texas, United States, 77030
      • Swedish Cancer Inst. | Seattle, Washington, United States, 98104
      • Bankstown-Lidcombe Hospital | Bankstown, New South Wales, Australia, 2200
      • St George Hospital | Kogarah, New South Wales, Australia, 2217
      • The Queen Elizabeth Hospital | Woodville, South Australia, Australia, 5011
      • Sunshine Hospital | St Albans, Victoria, Australia, 3021
      • Ottawa Hospital Research Institute | Ottawa, Ontario, Canada, K1Y 4E9
      • Centre hospitalier de l'Universite de Montreal (CHUM) | Montreal, Quebec, Canada, H2X 0A9
      • Jewish General Hospital | Montreal, Quebec, Canada, H3T 1E2
      • McGill University Health Centre - Glen Site | Montreal, Quebec, Canada, H4A 3J1
      • Peking Union Medical College Hospital | Beijing City, China, 100032
      • Beijing Friendship Hospital | Beijing, China, 100050
      • Beijing Cancer Hospital | Beijing, China, 100142
      • the First Hospital of Jilin University | Changchun, China, 130021
      • Jilin Cancer Hospital | Changchun, China, 132013
      • Hunan Cancer Hospital | Changsha CITY, China, 410013
      • The First People's Hospital of Foshan; Local Ethic Committee | Foshan, China, 510000
      • The 900th Hospital of PLA joint service support force | Fuzhou, China, 110016
      • Sun Yet-sen University Cancer Center | Guangzhou City, China, 510663
      • Nanfang Hospital, Southern Medical University | Guangzhou, China, 510515
      • Sir Run Run Shaw Hospital | Hangzhou City, China, 310018
      • Zhejiang Cancer Hospital; Zhejiang Cancer Hospital cancer department | Hangzhou City, China, 310022
      • The First Affiliated Hospital of College of Medicine, Zhejiang University | Hangzhou, China, 310003
      • Harbin Medical University Cancer Hospital | Harbin, China, 150081
      • Anhui Province Cancer Hospital | Hefei City, China, 230031
      • The First Affiliated Hospital of Anhui Medical University | Hefei, China, 230022
      • General Hospital of Jinan Military Command of PLA | Jinan, China, 250031
      • The 81st Hospital of P.L.A. | Nanjing City, China, 210002
      • Fudan University Shanghai Cancer Center | Shanghai City, China, 200120
      • Zhongshan Hospital Fudan University | Shanghai, China, 200032
      • Tongji Hosp, Tongji Med. Col, Huazhong Univ. of Sci. & Tech | Wuhan, China, 430030
      • Masarykuv onkologicky ustav | Brno, Czechia, 656 53
      • Fakultni nemocnice Olomouc; Onkologicka klinika | Olomouc, Czechia, 779 00
      • Hopital Claude Huriez;Gastro Enterologie | Lille, France, 59037
      • Hopital De La Croix Rousse; Hepatologie Gastro Enterologie | Lyon, France, 69317
      • Hopital Timone Adultes; Gastro Enterologie | Marseille, France, 13385
      • Hopital Saint-Eloi; Hepatologie-Gastro-Enterologie | Montpellier, France, 34295
      • Hopital Hotel Dieu Et Hme; Hepatologie Gastro Enterologie | Nantes, France, 44093
      • CHU Nice - Hôpital de l'Archet 2; service Hepato gastro enterologie | Nice Cedex, France, 06202
      • Hopital Charles Nicolle; Gastroenterologie | Rouen, France, 76031
      • Hopital Hautepierre; Gastro Enterologie | Strasbourg, France, 67098
      • Hôpital d'Adultes; Service hépato-gastro-entérologie | Vandoeuvre-les-nancy, France, 54511
      • Institut Gustave Roussy; Gastro-Enterologie | Villejuif, France, 94805
      • Campus Virchow-Klinikum Charité Centrum 13; Medizinische Klinik; Abt.Hepatologie u.Gastroenterologie | Berlin, Germany, 13353
      • Klinik Johann Wolfgang von Goethe Uni; Zentrum der Inneren Medizin; Medizinische Klinik I | Frankfurt, Germany, 60590
      • Universitaetsklinikum Hamburg-Eppendorf; I. Medizinische Klinik - Gastroenterologie | Hamburg, Germany, 20246
      • Med. Hochschule Hannover; Gastroenterologie | Hannover, Germany, 30625
      • Universitätsklinikum Leipzig Medizinische Klinik II Gastroenterolog. u. Hepatolog. | Leipzig, Germany, 04103
      • Uniklinik Mainz; I. Medizinische Klinik | Mainz, Germany, 55131
      • Klinikum der Uni Regensburg; Klinik f.Innere Medizin I Abt. Hämatologie und Internistische Onkologie | Regensburg, Germany, 93053
      • Queen Mary Hospital; Dept. Of Haematology & Oncology | Hong Kong, Hong Kong,
      • Prince of Wales Hosp; Dept. Of Clinical Onc | Shatin, Hong Kong,
      • Az. Osp. Rummo; Oncologia Medica | Benevento, Campania, Italy, 82100
      • IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola; Oncologia Medica | Meldola, Emilia-Romagna, Italy, 47014
      • Az. Osp. S. Luigi Gonzaga; Divisione Di Oncologia Medica | Orbassano, Piemonte, Italy, 10043
      • A.O.U. Cagliari-P.O. Monserrato;U.O. Oncologia | Cagliari, Sardegna, Italy, 09100
      • Azienda Ospedaliero - Universitaria Pisana U.O. Oncologia Medica 2 Universitaria ? Polo Oncologico | Pisa, Toscana, Italy, 56126
      • IRCCS Istituto Oncologico Veneto (IOV); Oncologia Medica Prima | Padova, Veneto, Italy, 35128
      • Chiba University Hospital | Chiba, Japan, 260-8677
      • National Cancer Center Hospital East | Chiba, Japan, 277-8577
      • Kurume University Hospital | Fukuoka, Japan, 830-0011
      • Sapporo Kosei Genaral Hospital | Hokkaido, Japan, 060-0033
      • Hokkaido University Hospital | Hokkaido, Japan, 060-8648
      • Kanazawa University Hospital | Ishikawa, Japan, 920-8641
      • Kitasato University Hospital | Kanagawa, Japan, 252-0375
      • Kumamoto University Hospital | Kumamoto, Japan, 860-8556
      • Osaka Metropolitan University Hospital | Osaka, Japan, 545-8586
      • Kindai University Hospital | Osaka, Japan, 589-8511
      • Saga-ken Medical Centre Koseikan | Saga, Japan, 840-8571
      • Shizuoka Cancer Center | Shizuoka, Japan, 411-8777
      • Japanese Red Cross Musashino Hospital | Tokyo, Japan, 180-8610
      • Chonnam National University Hwasun Hospital | Jeollanam-do, Korea, Republic of, 58128
      • Seoul National University Hospital | Seoul, Korea, Republic of, 03080
      • Severance Hospital, Yonsei University Health System | Seoul, Korea, Republic of, 03722
      • Asan Medical Center | Seoul, Korea, Republic of, 05505
      • Samsung Medical Center | Seoul, Korea, Republic of, 06351
      • Ulsan University Hosiptal | Ulsan, Korea, Republic of, 44033
      • Copernicus Podmiot Medyczny Sp. z o.o. Wojewodzkie Centrum Onkologii | Gdansk, Poland, 80-219
      • ID Clinic | Myslowice, Poland, 41-400
      • SP ZOZ MSWiA z WARMINSKO-MAZURSKIM CENTRUM ONKOLOGII; CLINICAL ONCOLOGY, CLINICAL IMMUNOLOGY | Olsztyn, Poland, 10-228
      • Narodowy Instytut Onkologii im. Marii Sk?odowskiej-Curie - Pa?stwowy Instytut Badawczy | Warszawa, Poland, 02-781
      • Dolno?l?skie Centrum Onkologii; Oddzia? Onkologii Klinicznej i Chemioterapii | Wroc?aw, Poland, 53-413
      • FSBI "National Medical Research Center of Oncology N.N. Blokhin?; Clinical Biotechnologies | Moscow, Moskovskaja Oblast, Russian Federation, 115478
      • GBUZ Saint Petersburg Clinical Research Center of Specialized Types of Care (Oncology) | Saint Petersburg, Sankt Petersburg, Russian Federation, 197758
      • National Cancer Centre | Singapore, Singapore, 169610
      • Tan Tock Seng Hospital; Oncology | Singapore, Singapore, 308433
      • Hospital Universitari Vall d'Hebron; Oncology | Barcelona, Spain, 08035
      • Hospital Clinico San Carlos; Servicio de Oncologia | Madrid, Spain, 28040
      • Hospital Universitario La Paz; Servicio de Oncologia | Madrid, Spain, 28046
      • Centro Integral Oncologico Clara Campal; Servicio de Oncología | Madrid, Spain, 28050
      • Hospital Universitario Miguel Servet; Servicio de Oncologia Medica | Zaragoza, Spain, 50009
      • National Cheng Kung University Hospital; Oncology | Tainan, Taiwan, 00704
      • Chi-Mei Medical Centre; Hematology & Oncology | Tainan, Taiwan, 710
      • Veterans General Hospital; Cancer Center | Taipei, Taiwan, 00112
      • National Taiwan Uni Hospital; Dept of Oncology | Taipei, Taiwan, 100
      • Chang Gung Memorial Hospital-Linkou; Dept of Oncology | Taoyuan County, Taiwan, 333
      • Beatson West of Scotland Cancer Centre | Glasgow, United Kingdom, G12 0YN
      • Royal Free Hospital; Dept of Oncology | London, United Kingdom, NW3 2QG
      • King'S College Hospital | London, United Kingdom, SE5 9RS
      • Christie Hospital Nhs Trust; Medical Oncology | Manchester, United Kingdom, M2O 4BX
      Investigators

        Study Documents (Full Text)

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        Additional Relevant MeSH Terms

        • Carcinoma
        • Carcinoma, Hepatocellular
        • Neoplasms, Glandular and Epithelial
        • Neoplasms by Histologic Type
        • Neoplasms
        • Adenocarcinoma
        • Liver Neoplasms
        • Digestive System Neoplasms
        • Neoplasms by Site
        • Digestive System Diseases
        • Liver Diseases