A Study of the Application of HAIC in Advanced HCC Previously Treated With ICIs and Antiangiogenic Agents

February 7, 2023 updated by: Ming Zhao, Sun Yat-sen University

A Study of the Application of Hepatic Arterial Infusion in Advanced Hepatocellular Carcinoma Previously Treated With Immune Checkpoint Inhibitors and Antiangiogenic Agents

Immune checkpoint inhibitors (ICIs) plus antiangiogenic agents can achieve better efficacy than sorafenib in the treatment of hepatocellular carcinoma (HCC) within a certain period of time, but more than half of the patients are still insensitive to the treatment. There is no evidence-based basis for second-line treatment after the progression of the disease.In view of the effectiveness of Hepatic arterial infusion (HAIC) in the first-line treatment of HCC in the Chinese population, this study intends to launch a prospective intervention study to explore the efficacy and safety of HAIC treatment in patients with advanced HCC after the failure of ICIs and antiangiogenic agents combination therapy, and to provide high-level evidence for optimizing the second-line treatment of advanced HCC in the future.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Each patient received an artery catheter procedure guided by digital subtraction angiography. Then, the FOLFOX (oxaliplatin 130 mg/m^2, leucovorin 200 mg/m^2, fluorouracil 400 mg/m^2, and fluorouracil 2,400 mg/m^2) regimen was sequentially infused through the catheter every cycle (3 weeks).A maximum of 4-6 courses of continuous hepatic artery infusion chemotherapy were received.If the patient has extrahepatic metastasis at baseline, ICIs should be used as a systemic treatment according to the severity of the disease. The drug type and treatment protocol of ICIs should be based on the most advanced treatment progress in the world.

Study Type

Interventional

Enrollment (Anticipated)

100

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China, 500060
        • Recruiting
        • Department of Minimally Invasive and Interventional Radiology, Liver Cancer Study and Service Group, Sun Yat-sen University Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

Cytohistological confirmation is required for diagnosis of HCC. Patients with advanced (unresectable and/or metastatic, stage C based on Barcelona-Clinic Liver Cancer [BCLC] staging classification) hepatocellular carcinoma.

At least one tumor lesion meeting measurable disease criteria as determined by RECIST v1.1.

Current cirrhotic status of Child-Pugh class A-B, with no encephalopathy. Ascites controlled by diuretics is permitted in this study.

Availability of a representative tumor tissue specimen (archival tumor tissue is allowed) at pre-screening.

Eastern Cooperative Oncology Group Scale for Assessment of Patient Performance Status ≤ 2.

Both men and women enrolled in this trial must use adequate barrier birth control measures during the course of the trial and 4 weeks after the completion of trial.

Adequate bone marrow, liver and renal function as assessed by central lab by means of the following laboratory requirements from samples within 7 days prior to procedure:

Hemoglobin > 100g/L Absolute neutrophil count >3.0 ×109/L Neutrophil count > 1.5 ×109/L Platelet count ≥ 50.0 ×109/L Total bilirubin < 51 μmol/L Alanine transaminase (ALT) and aminotransferase (AST) < 5 x upper limit of normal Albumin > 28 g/L Prothrombin time (PT)-international normalized ratio (INR) < 2.3, or PT < 6 seconds above control Serum creatinine < 110 μmol/L Willing and able to comply with scheduled visits, treatment plan and laboratory tests.

Exclusion Criteria:

Local treatments for HCC have been performed within 4 weeks, including surgical resection (including liver transplantation), local ablation, transcatheter arterial chemoembolization (TACE or TAE), radiotherapy (including brachytherapy).

A history of liver decompensation, such as refractory ascites, gastrointestinal bleeding, or hepatic encephalopathy; Uncontrolled complications, including but not limited to: Persistent or activity (except the HBV and HCV) infection, symptoms of congestive heart failure and uncontrolled diabetes, uncontrolled hypertension, unstable angina, uncontrolled arrhythmias, active ILD, severe chronic GI disease accompanied by diarrhea, or compliance with requirements may limit the research, resulted in significant increase risk of AE or influence Subjects provided psychiatric/social problem status on their ability to provide written informed consent. A history of active primary immunodeficiency or human immunodeficiency virus; Active or previous records of autoimmune disease or inflammatory diseases, including inflammatory bowel disease (e.g., colitis or Crohn's disease], diverticulitis, except [diverticulosis], systemic lupus erythematosus (SLE), sarcoidosis syndrome or Wegener syndrome (e.g., granulomatous vasculitis, gray's disease, rheumatoid arthritis, the pituitary gland inflammation and uveitis]).

Known to produce allergic or hypersensitive reactions to any study drug or any excipient thereof.

Significant clinical gastrointestinal bleeding or a potential risk of bleeding was identified by the investigator during the 30 days prior to study entry.

Tumors of the central nervous system, including metastatic brain tumors. Pregnant women or breast-feeding patients.

Complicated with other malignant tumors:

Malignant tumors that have been treated for therapeutic purposes, have no known active disease for 5 years prior to the first administration of the study drug, and have a low potential risk of recurrence.

Fully treated non-melanoma skin cancer or malignant freckle moles with no evidence of disease.

Fully treated carcinoma in situ without evidence of disease.

Is currently using, or has used an immunosuppressive drug within 14 days prior to the first dose of the investigational drug. This standard has the following exceptions:

intranasal, inhaled, topical or topical steroids. (e.g., intraarticular) Systemic corticosteroid therapy not exceeding 10 mg/ day of prednisone or its physiological equivalent as a prophylactic use of steroids for hypersensitivity. (e.g., CT scan pretherapy medication) Steroids as a prophylactic for allergic reactions. A live attenuated vaccine was administered within 30 days prior to the first administration of the study drug. Note: If enrolled, patients shall not receive live attenuated vaccine within 30 days of receiving study drug therapy and after the last administration of study drug.

Uncontrolled hypertension: systolic pressure ≥ 160 mmHg or diastolic pressure ≥ 100 mmHg despite anti-hypertension medications ≤ 28 days before randomization or first dose of drug.

Pregnant or lactating women, or fertile men or women who do not want to use high-efficiency contraceptives, 6 months after the last dosing of study treatment, from screening to study treatment. Based on the patient's preferred and customary lifestyle, abstinence during treatment and washout is an acceptable contraceptive method.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: HAIC
Treated by HAIC alone.
Procedure: digital subtraction angiography.
Each patient received an artery catheter procedure guided by digital subtraction angiography.
Drug: FOLFOX (oxaliplatin , leucovorin , fluorouracil , and fluorouracil )
Hepatic artery infusion chemotherapy. The FOLFOX (oxaliplatin 130 mg/m2, leucovorin 200 mg/m2, fluorouracil 400 mg/m2, and fluorouracil 2,400 mg/m2) regimen was sequentially infused through the catheter every cycle (3 weeks).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate (ORR)
Time Frame: 2-years Followed up
Tumor response to HAIC according to RECIST 1.1
2-years Followed up
Progress Free Survival (PFS)
Time Frame: 2-years Followed up
Absence of disease progression other than death
2-years Followed up

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Tumor local control
Time Frame: 2-years Followed up
Absence of regrowth inside the treated lesion
2-years Followed up
Adverse Events (AEs)
Time Frame: 2-years Followed up
Defined as the proportion of patients with AE, treatment-related AE (TRAE), immune-related AE (irAE), serious adverse event (SAE), assessed by NCI CTCAE v5.0
2-years Followed up
Overall Survival (OS)
Time Frame: 2-years Followed up
Absence of death of any cause
2-years Followed up

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sun Yat-sen University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

October 18, 2022

Primary Completion (ANTICIPATED)

October 18, 2025

Study Completion (ANTICIPATED)

October 18, 2026

Study Registration Dates

First Submitted

January 30, 2023

First Submitted That Met QC Criteria

February 7, 2023

First Posted (ACTUAL)

February 8, 2023

Study Record Updates

Last Update Posted (ACTUAL)

February 8, 2023

Last Update Submitted That Met QC Criteria

February 7, 2023

Last Verified

January 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • B2022-508-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe