High-risk hepatocellular carcinoma (HCC) MedDRA version: 21.0 Level: LLT Classification code 10019829 Term: Hepatocellular carcinoma recurrent System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Age >= 18 years - Participants with a first diagnosis of HCC who have undergone either a curative resection or ablation within 4-12 weeks prior to randomization (not applicable for crossover) - Documented diagnosis of HCC that has been completely resected or ablated (not applicable for crossover) - Absence of major macrovascular (gross vascular) invasion and of the portal vein (Vp3 or Vp4) or any grade of macrovascular invasion in the hepatic vein or inferior vena cava (not applicable for crossover) Note: Patients undergoing resection with minor vascular invasion of the portal vein (Vp1 or Vp2) as detected by either imaging or pathological examination are allowed - 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 - Negative HIV test at screening - Documented virology status of hepatitis, as confirmed by screening hepatitis B virus (HBV) and hepatitis C virus (HCV) tests - For patients with active HBV: HBV DNA =65 years) yes F.1.3.1 Number of subjects for this age range 265
Exclusion criteria
Exclusion criteria: - Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC - Evidence of residual, recurrent, or metastatic disease at randomization (not applicable for crossover) - 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 clinically significant 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, such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer - Active tuberculosis - Severe infection within 4 weeks prior to Day 1 of Cycle 1, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia, or any active infection that in the opinion of the investigator, could impact patient safety - Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to Day 1 of Cycle 1 - Prior allogeneic stem cell or solid organ transplantation - On the waiting list for liver transplantation - 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 - Co-infection with HBV and HCV - Co-infection with HBV and hepatitis D viral infection - Clinically significant uncontrolled or symptomatic hypercalcemia - History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins - Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab or bevacizumab formulations - Any treatment for HCC prior to resection or ablation, including systemic therapy and locoregional therapy such as TACE - Treatment with a live, attenuated vaccine within 4 weeks prior to Day 1 of Cycle 1, or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the final dose of atezolizumab - Treatment with investigational therapy within 4 weeks prior to Day 1 of Cycle 1 - Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-cytotoxic T lymphocyte-associated proteinCTLA- 4, anti-PD-1, and anti-PD-L1 therapeutic antibodies - Treatment with systemic immune stimulatory agents within 4 weeks or 5 drug elimination half-lives prior to Day 1 of Cycle 1 - Treatment with systemic immunosuppressive medication within 2 weeks prior to Day 1 of Cycle 1, or anticipation of need for systemic immunosuppressive medication during study treatment - Inadequately cont
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of atezolizumab plus bevacizumab compared with active surveillance on the basis of recurrence-free survival (RFS) as determined by an IRF;Secondary Objective: 1. To evaluate the efficacy of atezolizumab plus bevacizumab compared with active surveillance on the basis of overall survival (OS), RFS after randomization as determined by the investigator and by an Independent Review Facility (IRF), time to recurrence (TTR), IRF-assessed RFS and investigator-assessed RFS rate after randomization and OS rate at 24 months and 36 months, Time to extrahepatic spread or macrovascular invasion after randomization 2. To evaluate the safety of atezolizumab plus bevacizumab compared with active surveillance 3. To characterize the PK profile of atezolizumab when given in combination with bevacizumab 4. To evaluate the immune response to atezolizumab ;Primary end point(s): 1. IRF-assessed RFS;Timepoint(s) of evaluation of this end point: 1. Up to 91 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. OS rate at 24 months and 36 months 2. OS 3. RFS as determined by the investigator 4. TTR 5. Time to EHS or macrovascular invasion 6. RFS after randomization as determined by the investigator and by an IRF, among patients in the PD-L1-high subgroup 7. Incidence and severity of adverse events, with severity determined according to NCI CTCAE v5.0 8. Change from baseline in targeted vital signs 9. Change from baseline in targeted clinical laboratory test results 10. Serum concentration of atezolizumab at specified timepoints 11. Prevalence of anti-drug antibody (ADAs) to atezolizumab at baseline and incidence of ADAs to atezolizumab during the study 12. IRF-assessed RFS and investigator-assessed RFS rate at 24 and 36 months after randomization;Timepoint(s) of evaluation of this end point: 1. At 24 months and 36 months 2-7. Up to 91 months 8. From baseline (Days –28 to –1) to treatment/Surveillance Discontinuation or <= 30 days after final cycle 9. From baseline (Days -7 to -1) to treatment/Surveillance Discontinuation or <= 30 days after final cycle 10 and 11. Day 1 Cycle 1-4, 8 and 12, 16 and at treatment/Surveillance Discontinuation or <= 30 days after final cycle 12. At 24 months and 36 months | — |
Countries
Australia, Austria, Belgium, Brazil, Canada, China, Czechia, Czech Republic, France, Germany, Hong Kong, Italy, Japan, Korea, Republic of, Mexico, Netherlands, New Zealand, Peru, Poland, Russian Federation, Singapore, Spain, Taiwan, Thailand, Türkiye, United States
Contacts
Public ContactTrial Information Support Line-TISL
F. Hoffmann-La Roche Ltd
Outcome results
None listed