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
Condition: Carcinoma, Hepatocellular
MeSH terms: Carcinoma; Carcinoma, Hepatocellular; Recurrence
Intervention: Atezolizumab; Bevacizumab
Intervention description: Atezolizumab 1200 mg will be administered by IV infusion on Day 1 of each 21-day cycle.; Bevacizumab will be administered by IV infusion at a dose of 15 mg/kg on Day 1 of each 21-day cycle.
Intervention MeSH terms: Bevacizumab; Atezolizumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 668.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Participants with a first diagnosis of HCC who have undergone either a curative
             resection or ablation (radiofrequency ablation [RFA] or microwave ablation [MVA] only)
             within 4-12 weeks prior to randomization

          -  Documented diagnosis of HCC that has been completely resected or ablated (RFA or MVA
             only)

          -  Absence of major macrovascular invasion (except Vp1/Vp2) and extrahepatic spread

          -  Absence of extrahepatic spread as confirmed by CT or MRI scan of the chest, abdomen,
             pelvis, and head prior to and following curative procedure

          -  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

          -  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

          -  Have received more than 1 cycle of adjuvant TACE following surgical resection

          -  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

          -  Co-infection with HBV and hepatitis D viral infection

          -  Clinical significant 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 GI 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