Hepatocellular Carcinoma, Portal Vein Thrombosis
Conditions
Brief summary
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).
Interventions
RADIATIONPBT and atezolizumab/bevacizumab
Atezolizumab 1200 mg and bevacizumab 15 mg/Kg is administered IV infusion every 3 weeks. Proton beam therapy 30 - 50 Gy/5 fractions to portal vein tumor thrombosis with or without main primary tumor after 1 week (+/- 7 days) of 2nd cycle of atezolizumab and bevacizumab The follow-up phase begins when the decision to discontinue study is made. The follow-up phase is defined as the day after the end of study treatment until the day the subject dies.
Sponsors
Samsung Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with HCC meeting all of following criteria; 1. Histologically or radiologically confirmed hepatocellular carcinoma based on the guidelines of the Korean Liver Cancer Association-National Cancer Center 2022 2. Age \>= 20 3. 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. 4. Signed written informed consent 5. at least one or more measurable intrahepatic viable HCC lesions 6. Child-Pugh class A within 2 weeks from screening for study registration 7. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1 within 2 weeks from screening for study registration 8. Life expectancy of at least 16 weeks 9. 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 10. 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 11. If other selection conditions are satisfied and the
Exclusion criteria
are not met, registration is possible even in case of N1 or M1. 12. Registration is possible even in the case of hepatic vein tumor infiltration if other selection conditions are satisfied and the
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression-free survival rate | At 9 month |
| Incidence of adverse event assessed according to the Common Terminology Criteria for Adverse Events (CTCAE version 5.0) | From date of atezolizumab and bevacizumab initiatton until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 18 months |
Secondary
| Measure | Time frame |
|---|---|
| Overall survival rate | At 12 month |
| Time-to-progression | At 9 months |
| Objective response rate | At 3 month |
| Disease Control rate | At 3 month |
| Local tumor progression rate | At 12 month |
Countries
South Korea
Contacts
PRINCIPAL_INVESTIGATORJeong Il Yu, MD, PhD
Samsung Medical Center
Outcome results
None listed