Hepatic Arterial Infusion Chemotherapy in Combination With Atezolizumab and Bevacizumab for Second-line Treatment of Patients With Recurrent Liver Cancer After Liver Transplantation

Hepatic Arterial Infusion Chemotherapy in Combination With Atezolizumab and Bevacizumab for Second-line Treatment of Patients With Recurrent Liver Cancer After Liver Transplantation: an Open-label, Prospective, Single-center, Single-arm Clinical Study Protocol

For patients with recurrent liver cancer after liver transplantation, the median survival time is low and the prognosis is often poor. On the one hand, it is necessary to take into account the weakened effect of postoperative anti-rejection drugs with the use of immune checkpoint inhibitors, and on the other hand, the therapeutic effect of recurrent tumors should be taken into account. Both HAIC (hepatic arterial infusion chemotherapy) and T+A（Bevacizumab+Atezolizumab) have inhibitory effects on tumor, and we consider combining them organically to explore one that not only has a good inhibitory effect on tumor, but also better reduces the risk and degree of rejection. Therefore, in order to determine the feasibility and effectiveness of hepatic arterial infusion chemotherapy combined with Atezolizumab and Bevacizumab in the second-line treatment of patients with recurrent liver cancer after liver transplantation

Study Overview

• Status: Recruiting
• Conditions: Recurrent Liver Cancer After Liver Transplantation
• Intervention / Treatment: Drug: Hepatic arterial infusion chemotherapy + Atezolizumab and bevacizumab

• Study Type: Interventional
• Enrollment (Estimated): 25
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Hua Li, MD&PhD; Phone Number: 13060975202; Email: lihua100@yeah.net
• Study Contact Backup: Name: Siqi Li, MD&PhD; Phone Number: 17827065715; Email: Celiasiqi@163.com

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510630
      • Recruiting
      • Department of Liver Transplantation, the Third Affiliated Hospital of Sun Yat-sen University
      • Contact: Jianfeng Zhang, MD; Phone Number: 13935197625; Email: zhangjianfenggzq@163.com
      • Principal Investigator: Shuhong Yi, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥18 years old, ≤75 years old, gender unlimited;
2. hepatocellular carcinoma confirmed by pathology after liver transplantation;
3. CT and/or MRI confirmed tumor recurrence or metastasis, and the tumor recurrence and metastasis were not suitable for radical treatment such as surgical resection or ablation after multidisciplinary evaluation, and disease progression occurred after one first-line treatment regimen without immunotherapy;
4. There is at least one measurable recurrent or metastatic tumor lesion;
5. The expected survival time is more than 3 months;
6. Child-Pugh grade A and B (≤7 points);
7. Function of other vital organs: absolute neutrophil count ≥1.5×10E9/L; Platelet ≥50×10 e9 / L; Hemoglobin ≥9 g/dL; Serum albumin ≥2.8g/dL; Thyroid stimulating hormone (TSH)≤1 ULN(if TSH is abnormal, both T3 and T4 levels should be checked. If the levels of T3 and T4 were normal, the patients could be enrolled); Bilirubin ≤ 1.5x ULN; ALT and AST≤3 times ULN; Serum creatinine ≤1.5 ULN;
8. ECOG scored 0-2 points;
9. The patient fully understands and voluntarily signs the informed consent, and is willing and able to comply with the requirements of visit, treatment plan, laboratory examination and other requirements of the study schedule.

Exclusion Criteria:

1. Positive expression of PD-L1 in immunohistochemical liver biopsy (parenchymal or non-parenchymal cells of liver);
2. Allergic to bevacizumab and Atezolizumab;
3. ≥ grade II myocardial ischemia or myocardial infarction;
4. The hypertensive drugs cannot be controlled to the normal level (systolic blood pressure > 140mmHg, diastolic blood pressure > 90mmHg); Abnormal coagulation function (PT>16s, APTT>43s, TT>21s, Fbg <2g/L), a history of gastrointestinal bleeding within 6 months;
5. Patients with high risk of bleeding or receiving thrombolytic or anticoagulant treatment;
6. Autoimmune diseases include systemic lupus erythematosus, rheumatoid arthritis, psoriasis, etc.;
7. The primary liver disease of liver transplantation was autoimmune hepatitis, primary biliary cirrhosis, or primary sclerosing cholangitis;
8. interstitial pneumonia and other lung diseases, poor lung function;
9. Participate in clinical trials of other experimental drugs within 4 weeks;
10. infections requiring systemic treatment;
11. human immunodeficiency virus (HIV) positive infection;
12. Other factors that may affect safety or compliance;
13. During treatment of acute rejection or within 1 month after treatment;
14. Poor compliance.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Hepatic arterial infusion chemotherapy + Atezolizumab and bevacizumab; Hepatic arterial infusion chemotherapy: percutaneous introduction of a standard hepatic arterial catheter through the femoral artery. FOLFOX was sequentially transfused by a fixed catheter. Drugs:FOLFOX regimen: oxaliplatin, calcium folinate, and 5-FU. Atezolizumab: About 3 to 7 days after HAIC treatment, when liver function is stable (TBILI<2 times the upper limit of normal), Atezolizumab therapy can be started. The dosage was 1200mg and was given intravenously for at least 1 hour, once every 3 weeks. The longest course of treatment is 24 months. Bevacizumab: About 3 to 7 days after HAIC treatment, when liver function is stable (TBILI<2 times the upper limit of normal), bevacizumab therapy can be started. The dosage was 15mg/kg and was given intravenously for no less than 1 hour, once every 3 weeks. The longest course of treatment is 24 months.

Drug: Hepatic arterial infusion chemotherapy + Atezolizumab and bevacizumab; Drug: Oxaliplatin, calcium folinate, 5-FU, Atezolizumab and bevacizumab Procedure: HAIC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute graft rejection rate	defined as the incidence of acute graft rejection after HAIC combined with T+A.	3 months
Objective Response Rate	defined as the treatment response assessed by mRECIST after HAIC combined with T+A treatment	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	defined as the time from HAIC combined with T+A treatment to patient death from any cause.	1 year
Progression-free Survival	defined as the time from the start of HAIC combined with T+A treatment to the onset of tumor Progression or death from any cause.	1 year
Time to Progression	defined as the time from the start of HAIC combined with T+A treatment to tumor progression or death from any cause.	1 year
Serious Adverse Event	The incidence of serious adverse events caused by HAIC combined with T+A treatment.	1 year
Graft Rejection	defined as the incidence of transplant rejection during HAIC combined with T+A treatment.	1 year

Collaborators and Investigators

• Sponsor: Shuhong Yi
• Investigators: Study Director: Shuhong Yi, Third Affiliated Hospital, Sun Yat-Sen University

Study record dates

Study Major Dates

• Study Start (Actual): December 3, 2023
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): April 1, 2025

Study Registration Dates

• First Submitted: March 29, 2023
• First Submitted That Met QC Criteria: April 17, 2023
• First Posted (Actual): April 27, 2023

Study Record Updates

• Last Update Posted (Estimated): December 15, 2023
• Last Update Submitted That Met QC Criteria: December 11, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Hepatic arterial infusion chemotherapy; Bevacizumab; Atezolizumab
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Neoplasms by Site; Disease Attributes; Digestive System Neoplasms; Liver Diseases; Recurrence; Liver Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Immune Checkpoint Inhibitors; Bevacizumab; Atezolizumab
• Other Study ID Numbers: [2023]02-116-99

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No