C220 Liver cell carcinoma
Conditions
Interventions
Approximately 888 patients will be randomized in a 1:1:1 ratio to Arm A, Arm B, and Arm C to obtain approximately 379 RFS events. Randomization will be stratified by evidence of microvascular invasion
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1 Provision of signed and dated written informed consent form (ICF) and any locally required authorization (eg, Health Insurance Portability and Accountability Act in the US, EU Data Privacy Directive in the EU) obtained from the patient/legal representative prior to any mandatory study-specific procedures, sampling, and analyses, including screening evaluations. 2 Age =18 years at the time of screening. For patients aged 5 cm (iii) 4 or more tumors, =5 cm each (b) Ablation (radiofrequency or microwave, cryoablation, or PEI per institutional standard) and have the following radiologic findings prior to ablation: (i) Solitary tumor, 3 to 5 cm (ii) 2 to 4 tumors, =5 cm each (iii) Exclude patients with 5 or more tumors. 4 Patients must be randomized within 12 weeks after completion of curative hepatic resection or ablation. 5 Imaging to confirm disease-free status within 28 days prior to randomization. 6 Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 1 at enrollment. 7 Child-Pugh score of 5 or 6. 8 Patients with HBV infection (as characterized by positive hepatitis B virus surface antigen [HBsAg] and/or anti-hepatitis B core antibodies (HBcAbs) with detectable HBV deoxyribonucleic acid (DNA) [=10 IU/mL or above the limit of detection per local laboratory]) must receive antiviral therapy at least after enrollment (sign of ICF) per institutional practice to ensure adequate viral suppression (HBV DNA =2000 IU/mL) prior to randomization. Patients must remain on antiviral therapy for the study duration and for 6 months after the last dose of study treatment. Patients who test positive for anti HBcAb with undetectable HBV DNA (<10 IU/mL or under the limit of detection per local laboratory) do not require antiviral therapy. These patients will be tested at every cycle to monitor HBV DNA levels and initiate antiviral therapy if HBV DNA is detected (=10 IU/mL or above the limit of detection per local laboratory). Patients with detectable HBV DNA during the study must initiate and remain on antiviral therapy for the study duration and for 6 months after the last dose of study treatment.
Exclusion criteria
Exclusion criteria: 1 History of deep vein thrombosis, pulmonary embolism, or any other significant thromboembolism (venous port or catheter thrombosis or superficial venous thrombosis are not considered “significant”) during the 3 months prior to randomization. 2 History of significant bleeding disorders, vasculitis, or a significant bleeding episode from the GI tract within 3 months prior to study randomization. 3 History of GI perforation and/or fistulae within 6 months prior to randomization. 4 Any history of nephrotic or nephritic syndrome. 5 Evidence of symptomatic congestive heart failure (New York Heart Association II to IV) or symptomatic or poorly controlled cardiac arrhythmia. 6 History of arterial thrombotic event, including myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack, within 6 months prior to randomization. 7 Uncontrolled arterial hypertension defined by a systolic pressure =150 mm Hg or diastolic pressure =90 mm Hg despite standard medical management. 8 Serious or non-healing wound, peptic ulcer, or bone fracture within 28 days prior to randomization. 9 Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC. 10 Evidence of esophageal and/or gastric varices on upper endoscopy or contrast-enhanced cross-sectional imaging. 11 Evidence of metastasis, macrovascular invasion, or co-existing malignant disease on baseline imaging.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Investigator tumor assessments will be performed using modified Response Evaluation Criteria in Solid Tumors (mRECIST 1.1) criteria. NAME OF THE RESULT: Recurrence-free survival (RFS) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: On-study tumor assessments (CT or MRI of the chest, abdomen, and pelvis) will occur Q12W (±1 week) following randomization for the first 24 months and then Q24W (±1 week) until Investigator-determined radiologic recurrence. | — |
Secondary
| Measure | Time frame |
|---|---|
| Investigator tumor assessments will be performed using modified Response Evaluation Criteria in Solid Tumors (mRECIST 1.1) criteria. NAME OF THE RESULT: Recurrence-free survival (RFS) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: On-study tumor assessments (CT or MRI of the chest, abdomen, and pelvis) will occur Q12W (±1 week) following randomization for the first 24 months and then Q24W (±1 week) until Investigator-determined radiologic recurrence.;Include OS; RFS, recurrence-free survival at 24 months (RFS24), recurrence-free survival at 36 months (RFS36), and time to recurrence (TTR) derived (by AstraZeneca) from BICR assessments according to RECIST 1.1; and time from randomization to recurrence/progression on the next therapy (RFS2/PFS2) as assessed by the Investigator according to local standard clinical practice. NAME OF THE RESULT: Overall Survival OS; recurrence-free survival (RFS(, recurrence-free survival at 24 months (RFS24), recurrence-free survival at 36 months (RFS36), and time to recurrence (TTR) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: Following completion or discontinuation of study treatment, assessments for survival must be made at Months 3, 6, and 9 (±1 week); Month 12 (±2 weeks); and then every 6 months (±2 weeks) thereafter. | — |
Countries
Australia, Austria, Brazil, Canada, China, France, Germany, Italy, Japan, Korea South, Taiwan, Thailand, Turkey, United States
Outcome results
None listed