Proton Beam Radiotherapy Followed by Tecentriq and Avastin for Primary Liver Cancer With Vp2-4 Portal Vein Invasion: PORTAL Study
This study is investigator initiated, single-institution, prospective, phase 2 open-label study to determine the efficacy and safety of combination therapy of atezolizumab/bevacizumab and proton beam therapy to portal vein tumor thrombosis with or without main primary tumor in patients with stage 3 or higher hepatocellular carcinoma (HCC) with Vp2-4 portal vein invasion who had not undergone systemic therapy for HCC. The primary endpoint of this study is progression-free survival and secondary endpoints are overall survival (OS), time to progression (TTP), objective response rate, disease control rate (DCR), and time to local disease progression (LTP).
• Patients with HCC meeting all of following criteria;
‣ Histologically or radiologically confirmed hepatocellular carcinoma based on the guidelines of the Korean Liver Cancer Association-National Cancer Center 2022
⁃ Age \>= 20
⁃ Vp2-4 portal vein tumor thrombosis diagnosed by dynamic enhanced computed tomography (CT) or maganetic resonance images (MRI) with below finding 1) an intraluminal filling defect adjacent to the primary tumor in Vp2-4 portal vein 2) an enhancement of the filling defect on arterial phase and a washout on portal/delayed phases.
⁃ Signed written informed consent
⁃ at least one or more measurable intrahepatic viable HCC lesions
⁃ Child-Pugh class A within 2 weeks from screening for study registration
⁃ Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1 within 2 weeks from screening for study registration
⁃ Life expectancy of at least 16 weeks
⁃ adequate bone marrow and liver function within 2 weeks from screening for study registration
∙ Hemoglobin ≥ 9.0 g/dL
• Absolute neutrophil count (ANC) ≥ 1,000/mm3
⁃ Platelet count ≥ 50,000/μL
‣ Total bilirubin \< 2.5 mg/dL
∙ Serum albumin \>2.8 g/dL
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 × upper limit of normal (ULN)
⁃ Prothrombin time in INR ≤ 1.8 × ULN
‣ Serum creatinine ≤ 1.5 mg/dL
‣ Women of childbearing potential and men must agree to use highly efficient contraception since signing of the informed consent form until at least 6 months (women) and 7 months (men) after the last study drug administration
‣ If other selection conditions are satisfied and the exclusion criteria are not met, registration is possible even in case of N1 or M1.
‣ Registration is possible even in the case of hepatic vein tumor infiltration if other selection conditions are satisfied and the exclusion criteria are not met
‣ no limitation according to the size and number of tumors in the liver.