Infusion of immune inhibitors for liver cancer treatment

A Phase II/III Randomized Trial of Comparison of Survival Benefit of Administration of PD1/PDL1/CTLA4 Inhibitor or Their Combinations Via Hepatic Arterial Infusion Versus Vein for Immunotherapy of Advanced Liver Cancer

This study is testing whether delivering immune inhibitors directly into the liver can help people with advanced liver cancer live longer and feel better compared to traditional methods.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 200 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Second Affiliated Hospital of Guangzhou Medical University (Academic / other)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Guanzhou, Guangdong)
• Trial ID: NCT03949231 on ClinicalTrials.gov

What this trial studies

This trial investigates the survival outcomes, response rates, and safety of patients with advanced liver cancer by comparing the infusion of PD1/PDL1/CTLA4 inhibitors through the hepatic artery versus the vein. Given the high mortality rate of liver cancer, particularly in China, this study aims to explore a more effective treatment method that could enhance local drug concentration at the tumor site while minimizing systemic side effects. The trial includes patients diagnosed with unresectable hepatocellular carcinoma who have limited treatment options available. By utilizing the hepatic arterial infusion method, the study seeks to improve the efficacy of existing immunotherapies.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 80 with advanced hepatocellular carcinoma who are not suitable for surgery or have progressed after previous treatments.

Not a fit: Patients with early-stage liver cancer or those who are not diagnosed with hepatocellular carcinoma will not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could provide a more effective treatment option for patients with advanced liver cancer, potentially improving survival rates and quality of life.

How similar studies have performed: While the use of PD1/PDL1 inhibitors has been explored in various cancers, this specific approach of hepatic arterial infusion for liver cancer is relatively novel and has not been extensively tested in prior studies.

Eligibility criteria

Inclusion Criteria:

1. Cytohistological confirmation is required for diagnosis of HCC.、
2. Signed informed consent before recruiting
3. Age between 18 to 80 years with estimated survival over 3 months.
4. Child-Pugh class A or B/Child score \> 7; ECOG score \< 2
5. Tolerable coagulation function or reversible coagulation disorders
6. Laboratory examination test within 7 days prior to procedure: WBC≥3.0×10E9/L; Hb≥90g/L； PLT ≥50×10E9/L；INR \< 2.3 or PT \< 6 seconds above control；Cr ≤ 145.5 umul/L；Albumin \> 28 g/L；Total bilirubin \< 51 μmol/L
7. At least one tumor lesion meeting measurable disease criteria as determined by RECIST v1.1.
8. Patients with advanced (unresectable and/or metastatic, stage C based on Barcelona-Clinic Liver Cancer \[BCLC\] staging classification) hepatocellular carcinoma which would not be suitable for treatment with loco-regional therapies or have progressed following locoregional therapy such as surgical resection, percutaneous hepatic arterial embolization, radiofrequency ablation, and percutaneous interventional therapy.
9. Birth control.
10. Willing and able to comply with scheduled visits, treatment plan and laboratory tests.

Exclusion Criteria:

1. Patients participated in clinical trials of equipment or drugs (signed informed consent) within 4 weeks;
2. Patients accompany by ascites, hepatic encephalopathy and esophageal and gastric varices bleeding;
3. Any serious accompanying disease, which is expected to have an unknown, impact on the prognosis, include heart disease, inadequately controlled diabetes and psychiatric disorders;
4. Patients accompanied with other tumors or past medical history of malignancy;
5. Pregnant or lactating patients, all patients participating in this trial must adopt appropriate birth control measures during treatment;
6. Patients have poor compliance.

   Any contraindications for hepatic arterial infusion procedure:

   A.Impaired clotting test (platelet count \< 60000/mm3, prothrombin activity \< 50%).

   B.Renal failure / insufficiency requiring hemo-or peritoneal dialysis. C.Known severe atheromatosis. D.Known uncontrolled blood hypertension (\> 160/100 mm/Hg).
7. Patients have the past history of liver cancer treatment, such as transplantation, resection, radiotherapy, chemotherapy and so on;
8. Allergic to adriamycin chemotherapy drugs，contrast agent and lipiodol;
9. Any agents which could affect the absorption or pharmacokinetics of the study drugs
10. Subjects unable to suffer the discomfort of the HAI procedure

Where this trial is running

Guanzhou, Guangdong

• The Second Affiliated Hospital of Guangzhou Medical University — Guanzhou, Guangdong, China (Recruiting)

Study contacts

• Principal investigator: Hui Lian, MD — Second Affiliated Hospital of Guangzhou Medical University
• Study coordinator: Hui Lian, MD

Conditions Liver Cancer; PD1 antibody; Artery infusion; PDL1 antibody; CTLA4 antibody