Locoregional Therapy Combined With Bevacizumab and PD1/L1 Inhibitor in Advanced Hepatocellular Carcinoma

Advanced Hepatocellular Carcinoma Clinical Trial

Official title:

Efficacy of Locoregional Therapy Combined With Bevacizumab and PD1/L1 Inhibitor in Advanced Hepatocellular Carcinoma: a Multicenter, Observational, Real-world Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06323382
• Other study ID #: Liver Project 6
• Status: Recruiting
• Start date: January 1, 2021
• Est. completion date: December 30, 2024

Study information

• Verified date: March 2024
• Source: Sun Yat-sen University
• Contact: Qunfang Zhou, MD
• Phone: 86 19868000115
• Email: zhouqun988509[@]163.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Atezolizumab + Bevacizumab was superior to sorafenib in overall survival in advanced hepatocellular carcinoma. The programmed cell death protein-1 (PD1) and PDL1 inhibitor, was effective and tolerable in patients with advanced hepatocellular carcinoma. We aimed to describe the efficacy and safety of locoregional therapy combined with Bevacizumab and PD1/L1 inhibitor in patients with advanced hepatocellular carcinoma who can not receive radical therapy.

Description:

This study is a multicenter, observational real-world study to explore the efficacy, safety of locoregional therapy combined with Bevacizumab and PD1/L1 inhibitor in advanced hepatocellular carcinoma. This study focused on the management of locoregional therapy combined with Bevacizumab and PD-1/L1 inhibitor. This study will create a database that will provide clinical parameters and outcomes of patients undergoing locoregional therapy combined Bevacizumab and PD-1/L1 inhibitor as standard of care in hopes of answering key clinical questions.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 240
• Est. completion date: December 30, 2024
• Est. primary completion date: December 30, 2024
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. HCC diagnosed by histopathological examination or Guidelines for Diagnosis and Treatment of Primary Liver Cancer or the recurrent HCC after surgery;

2. age between 18 and 75 years;

3. Stage B (middle stage) or C (late stage) HCC determined in accordance with Barcelona Clinic Liver Cancer staging system (BCLC stage).

4. Locoregional therapy include TACE or HAIC, locoregional combined with Bevacizumab and PD1/L1 inhibitor as firstline therapy; non-firstline therapy (previous use of any systemic therapy but intolerant or drug resistant).

5. Child-Pugh class A or B;

6. Eastern Cooperative Group performance status (ECOG) score of 0-2;

7. Hemoglobin = 8.5 g/dL Total bilirubin = 30mmol/L Serum albumin = 32 g/L ASL and AST = 5 x upper limit of normal Serum creatinine = 1.5 x upper limit of normal INR = 1.5 or PT/APTT within normal limits Absolute neutrophil count (ANC) >1,500/mm3

8. Prothrombin time =18s or international normalized ratio < 1.7.

9. Ability to understand the protocol and to agree to and sign a written informed consent document.

Exclusion Criteria:

1. Cholangiocellular carcinoma (ICC).

2. Patients without image information should be excluded;

3. The survival or patients less than 3 months.

4. Serious medical comorbidities.

5. Evidence of hepatic decompensation including ascites, gastrointestinal bleeding or hepatic encephalopathy.

6. Known history of HIV.

7. History of organ allograft.

8. Known or suspected allergy to the investigational agents or any agent given in association with this trial.

9. Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.

10. Evidence of bleeding diathesis.

11. Patients with clinically significant gastrointestinal bleeding within 30 days prior to study entry.

Related Conditions & MeSH terms

• Advanced Hepatocellular Carcinoma
• Bevacizumab
• Carcinoma
• Carcinoma, Hepatocellular

Intervention

Procedure:
• Locoregional therapy
TACE procedure The decision to utilize transarterial artery chemoembolization (TACE) was performed through the tumor-feeding artery. The embolization emulsion was a mixture of Epirubicin 30-60 mg, Lobaplatin 30-50 mg, and Lipiodol 10-30 ml, and it was infused into tumor-feeding arteries via a 2.7/2.8 Fr micro-catheter. HAIC procedure Hepatic arterial infusion chemotherapy (HAIC) procedure was performed with FOLFOX regimen: 85 or 135 mg/m2 oxaliplatin from hour 0 to 2 on day 1400 mg/m2 leucovorin from hour 2 to 4 on day 1, and 400 mg/m2 fluorouracil bolus at hour 5 on the day 1; and 2400 mg/m2 fluorouracil over 46 h on days 1 and 2.

Drug:
• Bevacizumab
15mg/kg or 7.5mg/kg intravenously every 3 weeks
• Atezolizumab
1200mg intravenously every 3 weeks
• Tislelizumab
200mg intravenously every 3 weeks
• Toripalimab
220mg intravenously every 3 weeks
• Sintilimab
200mg intravenously every 3 weeks
• Camrelizumab
200mg intravenously every 3 weeks

Locations

Country	Name	City	State
China	Chinese PLA hospital	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Sun Yat-sen University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-Free-Survival (PFS)	Progression was defined as progressive disease by independent radiologic review	12 months
Secondary	Overall survival (OS)	OS is the length of time from the date of inclusion until death from any cause.	24 months
Secondary	Objective response rate (ORR)	ORR, as determined based on tumor response according to RECIST 1.1, is defined as the proportion of all included patients whose best overall response (BOR) is either a complete response or partial response.	12 months
Secondary	Adverse events	Safety will be evaluated according to the NCI CTCAE Version 4.03. All observations	24 months