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A Study of Atezolizumab Plus Bevacizumab Versus Active Surveillance as Adjuvant Therapy in Patients With Hepatocellular Carcinoma at High Risk of Recurrence After Surgical Resection or Ablation

NCT04102098

Description:

This study will evaluate the efficacy and safety of adjuvant therapy with atezolizumab plus bevacizumab compared with active surveillance in participants with completely resected or ablated hepatocellular carcinoma (HCC) who are at high risk for disease recurrence.

Related Conditions:
  • Hepatocellular Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: A Study of Atezolizumab Plus Bevacizumab Versus Active Surveillance as Adjuvant Therapy in Patients With Hepatocellular Carcinoma at High Risk of Recurrence After Surgical Resection or Ablation
  • Official Title: A Phase III, Multicenter, Randomized, Open-Label Study of Atezolizumab (Anti-PD-L1 Antibody) Plus Bevacizumab Versus Active Surveillance as Adjuvant Therapy in Patients With Hepatocellular Carcinoma at High Risk of Recurrence After Surgical Resection or Ablation

Clinical Trial IDs

  • ORG STUDY ID: WO41535
  • SECONDARY ID: 2019-002491-14
  • NCT ID: NCT04102098

Conditions

  • Carcinoma, Hepatocellular

Interventions

DrugSynonymsArms
AtezolizumabTecentriqArm A (atezolizumab plus bevacizumab)
BevacizumabAvastinArm A (atezolizumab plus bevacizumab)

Purpose

This study will evaluate the efficacy and safety of adjuvant therapy with atezolizumab plus bevacizumab compared with active surveillance in participants with completely resected or ablated hepatocellular carcinoma (HCC) who are at high risk for disease recurrence.

Trial Arms

NameTypeDescriptionInterventions
Arm A (atezolizumab plus bevacizumab)ExperimentalParticipants will receive Atezolizumab + Bevacizumab until disease recurrence or unacceptable toxicity.
  • Atezolizumab
  • Bevacizumab
Arm B (active surveillance)No InterventionActive surveillance of participants.

    Eligibility Criteria

            Inclusion Criteria:
    
              -  Participants with a first diagnosis of HCC who have undergone a curative resection or
                 ablation (radiofrequency ablation [RFA] or microwave ablation [MVA] only)
    
              -  Documented diagnosis of HCC that has been completely resected or ablated (RFA or MVA
                 only)
    
              -  Absence of macrovascular (gross vascular) invasion and absence of extrahepatic spread
                 (EHS)
    
              -  Full recovery from surgical resection or ablation within 4 weeks prior to
                 randomization
    
              -  High risk for HCC recurrence after resection or ablation
    
              -  For patients who received post-operative transarterial chemoembolization: full
                 recovery from the procedure within 4 weeks prior to randomization
    
              -  For patients with resected HCC, availability of a representative baseline tumor tissue
                 sample
    
              -  ECOG Performance Status of 0 or 1
    
              -  Child-Pugh Class A status
    
              -  Adequate hematologic and end-organ function
    
              -  For women of childbearing potential: agreement to remain abstinent (refrain from
                 heterosexual intercourse) or use contraceptive methods
    
              -  For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use
                 a condom, and agreement to refrain from donating sperm
    
            Exclusion Criteria:
    
              -  Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC
    
              -  Recurrent HCC prior to randomization
    
              -  Evidence of residual, recurrent, or metastatic disease at randomization
    
              -  Clinically significant ascites
    
              -  History of hepatic encephalopathy
    
              -  Prior bleeding event due to untreated or incompletely treated esophageal and/or
                 gastric varices within 6 months prior to randomization
    
              -  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 CT scan
    
              -  Significant cardiovascular disease within 3 months prior to Day 1 of Cycle 1, unstable
                 arrhythmia, or unstable angina
    
              -  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
    
              -  Active tuberculosis
    
              -  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
    
              -  Pregnant or breastfeeding, or intending to become pregnant during the study or within
                 5 months after the final dose of atezolizumab or within 6 months after the final dose
                 of bevacizumab. Women of childbearing potential must have a negative serum pregnancy
                 test result within 14 days prior to Day 1 of Cycle 1.
    
              -  Co-infection with HBV and HCV.
    
              -  Uncontrolled or symptomatic hypercalcemia
    
              -  Any treatment for HCC prior to resection or ablation, including systemic therapy and
                 locoregional therapy such as TACE
    
              -  Treatment with systemic immunostimulatory or immunosuppressive agents
    
              -  Inadequately controlled arterial hypertension
    
              -  History of hypertensive crisis or hypertensive encephalopathy
    
              -  Significant vascular disease
    
              -  Evidence of bleeding diathesis or significant coagulopathy
    
              -  Current or recent use of aspirin or full-dose oral or parenteral anticoagulants
    
              -  Core biopsy within 3 days of Day 1 of Cycle 1
    
              -  History of abdominal or tracheoesophageal fistula, GI perforation, or intra-abdominal
                 abscess
    
              -  Serious non-healing or dehiscing wound
    
              -  Major surgical procedure within four weeks
    
              -  Chronic daily treatment with a non-steroidal anti-inflammatory drug
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Recurrence-Free Survival (RFS), as Determined by IRF
    Time Frame:Baseline up to approximately 91 months
    Safety Issue:
    Description:RFS is defined as the time from randomization to the first documented occurrence of local, regional, or metastatic HCC as determined by an IRF, or death from any cause (whichever occurs first).

    Secondary Outcome Measures

    Measure:Overall Survival (OS)
    Time Frame:Baseline up to approximately 91 months
    Safety Issue:
    Description:OS is defined as the time from randomization to death from any cause.
    Measure:RFS as Determined by the Investigator
    Time Frame:Baseline up to approximately 91 months
    Safety Issue:
    Description:RFS is defined as the time from randomization to the first documented occurrence of local, regional, or metastatic HCC as determined by an investigator, or death from any cause (whichever occurs first).
    Measure:Time to Recurrence (TTR)
    Time Frame:Baseline up to approximately 91 months
    Safety Issue:
    Description:TTR defined as the time from randomization to first documented occurrence of local, regional, or etastatic HCC, as determined by the investigator and by an IRF.
    Measure:OS Rate at 24 Months
    Time Frame:Baseline to 24 months
    Safety Issue:
    Description:OS rate defined as the proportion of patients who have not experienced death from any cause at 24 months after randomization.
    Measure:OS Rate at 36 Months
    Time Frame:Baseline to 36 months
    Safety Issue:
    Description:OS rate defined as the proportion of patients who have not experienced death from any cause at 36 months after randomization.
    Measure:Time to Extrahepatic Spread (EHS) or Macrovascular Invasion
    Time Frame:Baseline up to approximately 91 months
    Safety Issue:
    Description:Time to EHS or macrovascular invasion after randomization, defined as the time from randomization to the first appearance of EHS or macrovascular invasion, as determined by the investigator and by an IRF.
    Measure:RFS in Pd-L1-High Subgroup
    Time Frame:Baseline up to approximately 91 months
    Safety Issue:
    Description:RFS after randomization as determined by the investigator and by an IRF, among patients in the PD-L1-high subgroup.
    Measure:Percentage of Participants With Adverse Events
    Time Frame:Baseline up to approximately 91 months
    Safety Issue:
    Description:
    Measure:Serum Concentration of Atezolizumab
    Time Frame:Prior to any drug administration on Day 1 of Cycles 1, 2, 3, 4, 8, 12, and 16 (each cycle is 21 days)
    Safety Issue:
    Description:
    Measure:Number of Participants with Anti-Drug Antibodies (ADAs) to Atezolizumab
    Time Frame:Prior to any drug administration on Day 1 of Cycles 1, 2, 3, 4, 8, 12, and 16 (each cycle is 21 days)
    Safety Issue:
    Description:

    Details

    Phase:Phase 3
    Primary Purpose:Interventional
    Overall Status:Not yet recruiting
    Lead Sponsor:Hoffmann-La Roche

    Last Updated