Proton Beam Radiotherapy Followed by Tecentriq and Avastin for Primary Liver Cancer With Vp2-4 Portal Vein Invasion

Hepatocellular Carcinoma Clinical Trial

Official title:

Proton Beam Radiotherapy Followed by Tecentriq and Avastin for Primary Liver Cancer With Vp2-4 Portal Vein Invasion: PORTAL Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05625893
• Other study ID #: PORTAL
• Status: Recruiting
• Phase: Phase 2
• Start date: September 16, 2022
• Est. completion date: December 31, 2025

Study information

• Verified date: November 2022
• Source: Samsung Medical Center
• Contact: Jeong Il Yu, MD, PhD
• Phone: 82-2-3410-9598
• Email: ro.yuji651[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 63
• Est. completion date: December 31, 2025
• Est. primary completion date: September 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

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 exclusion criteria are not met

13. no limitation according to the size and number of tumors in the liver.

Exclusion Criteria:

Patients with HCC meeting all of following criteria;

1. previous history of systemic treatment for HCC (If systemic treatment for HCC has been performed at least once, it will not be enrolled in this study.) However, registration is permitted if the previous systemic treatment is for adjuvant purposes or treatment for other cancers. Also allowed if previous HCC treatment is local treatment. However, cases with a history of previous upper abdominal radiotherapy (including proton therapy and heavy particle therapy) are excluded.

2. any type of anticancer agent (including investigational) within 2 weeks before enrollment

3. Having active brain metastasis or leptomeningeal metastasis need surgery or steroid therapy

4. Moderate to severe or intractable ascites

5. A history or presence of hepatic encephalopathy

6. Presence of active bacterial infection

7. Untreated active chronic hepatitis B or active hepatitis C

8. History of portal hypertension with bleeding within the past 6 months

9. Prior liver transplant

10. Uncontrolled severe medical comorbidity

11. unhealed wound

12. uncontrolled electrolyte imbalance

13. Non-interruptible therapeutic use of anticoagulants or thrombolytics

14. History of uncontrolled or autoimmune disease, or immunocompromised

15. interstitial lung disease

16. Other malignant disease (a history of treated malignancy -other than HCC- is allowable if the patient's malignancy has been in complete remission, off chemotherapy and without additional surgical intervention, during the preceding two years)

17. Mentally retarded/medically incapable of consent

Related Conditions & MeSH terms

• Hepatocellular Carcinoma
• Liver Neoplasms
• Portal Vein Thrombosis
• Thrombosis

Intervention

Radiation:
• PBT 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.

Locations

Country	Name	City	State
Korea, Republic of	Samsung Medical Center	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Samsung Medical Center

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival rate		At 9 month
Primary	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	Overall survival rate		At 12 month
Secondary	Time-to-progression		At 9 months
Secondary	Objective response rate		At 3 month
Secondary	Disease Control rate		At 3 month
Secondary	Local tumor progression rate		At 12 month