HAIC Plus A+T for Patients With High-risk HCC: a Single-arm Phase 2 Trial

Sponsor

Sun Yat-sen University (Other)

Overall Status

Recruiting

CT.gov ID

NCT05886465

Collaborator

(none)

Enrollment

Location

Arm

18.3

Anticipated Duration (Months)

2.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Atezolizumab plus bevacizumab is the first-line treatment for patients with advanced hepatocellular carcinoma. However, the prognosis for high-risk hepatocellular carcinoma is still poor, with a median overall survival of 7.6 months. Hepatic arterial infusion chemotherapy of oxaliplatin, 5-fluorouracil and leucovorin is effective in large hepatocellular carcinoma or hepatocellular carcinoma with major portal vein tumor thrombus. Our previous showed that hepatic arterial infusion chemotherapy plus lenvatinib and toripalimab (programmed cell death protein-1 antibody) had a powerful anti-tumor effect for high-risk hepatocellular carcinoma, with a median overall survival of 18 months. Thus, the purpose of this study is to evaluate the efficacy and safety of hepatic arterial infusion chemotherapy of oxaliplatin, 5-fluorouracil and leucovorin plus atezolizumab plus bevacizumab for patients with high-risk hepatocellular carcinoma.

Condition or Disease	Intervention/Treatment	Phase
Hepatocellular Carcinoma	Drug: Atezolizumab Drug: Bevacizumab Procedure: HAIC with FOLFOX	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

40 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Hepatic Arterial Infusion Chemotherapy With FOLFOX Plus Atezolizumab and Bevacizumab for Patients With High-risk Hepatocellular Carcinoma: a Single-arm Phase 2 Trial

Actual Study Start Date :

May 24, 2023

Anticipated Primary Completion Date :

Jun 1, 2024

Anticipated Study Completion Date :

Dec 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: HAIC plus A+T	Drug: Atezolizumab 1200 mg, iv.drip, Q3W Drug: Bevacizumab 15mg/kg, iv.drip, Q3W Procedure: HAIC with FOLFOX administration of oxaliplatin , fluorouracil, and leucovorin via the tumor feeding arteries, Q3W

Arm

Intervention/Treatment

Experimental: HAIC plus A+T

Drug: Atezolizumab

1200 mg, iv.drip, Q3W

Drug: Bevacizumab

15mg/kg, iv.drip, Q3W

Procedure: HAIC with FOLFOX

administration of oxaliplatin , fluorouracil, and leucovorin via the tumor feeding arteries, Q3W

Outcome Measures

Primary Outcome Measures

Progression free survival rate at 6 months [6 months]
Progression was defined as progressive disease by independent radiologic review according to RECIST 1.1 or death from any cause

Secondary Outcome Measures

Overall survival (OS) [6 months]
OS is the length of time from the date of randomization until death from any cause.
Progression free survival (PFS) [6 months]
PFS is defined as the time from the date of randomization to the date of the first objectively documented tumor progression or death due to any cause.
Objective response rate (ORR) [6 months]
ORR, as determined based on tumor response according to RECIST 1.1, is defined as the proportion of all randomized subjects whose best overall response (BOR) is either a CR or PR.
Adverse events [30 days]
Safety will be evaluated according to the NCI CTCAE Version 4.03. All observations pertinent to the safety of the study medication will be recorded on the CRF and included in the final report.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

The diagnosis of HCC was based on the diagnostic criteria for HCC used by the European Association for the Study of the Liver (EASL)
Patients must have at least one tumor lesion that can be accurately measured according to EASL criteria.
Barcelona clinic liver cancer-stage C
High risk disease: Vp-4 based on the Japanese standard, bile duct invasion, or tumor occupancy ≥50% of the liver
Eastern Cooperative Oncology Group performance status of 0 to 2
With no previous treatment
No Cirrhosis or cirrhotic status of Child-Pugh class A only
Not amendable to surgical resection ,local ablative therapy and any other cured treatment.
The following laboratory parameters:

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

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

Exclusion Criteria:

Evidence of hepatic decompensation including ascites, gastrointestinal bleeding or hepatic encephalopathy
Known history of HIV
History of organ allograft
Known or suspected allergy to the investigational agents or any agent given in association with this trial.
Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy
Evidence of bleeding diathesis.
Patients with clinically significant gastrointestinal bleeding within 30 days prior to study entry.
Known central nervous system tumors including metastatic brain disease