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HAIC Combined With Bevacizumab and Toripalimab for Advanced Hepatocellular Carcinama

Primary Purpose

Hepatocellular Carcinoma, Bevacizumab, Liver Neoplasms

Status

Unknown status

Phase

Phase 2

Locations

Study Type

Interventional

Intervention

Hepatic arterial infusion chemotherapy

Bevacizumab

Toripalimab

About this trial

This is an interventional treatment trial for Hepatocellular Carcinoma

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

HCC diagnosed by histopathological examination or Guidelines for Diagnosis and Treatment of Primary Liver Cancer or the recurrent HCC after surgery;
age between 18 and 75 years;
Stage B (middle stage) or C (late stage) HCC determined in accordance with Barcelona Clinic Liver Cancer staging system (BCLC stage). In case of stage B.
No previous use of any systemic therapy or recurrent HCC.
Child-Pugh class A or B;
Eastern Cooperative Group performance status (ECOG) score of 0-2;
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
Prothrombin time ≤18s or international normalized ratio < 1.7.
Ability to understand the protocol and to agree to and sign a written informed consent document.

Exclusion Criteria:

Cholangiocellular carcinoma (ICC);
Patients with cancer thrombus in the main trunk of portal vein (Vp4), or cancer thrombus in inferior vena cava should be excluded;
Accepting ablation or surgery or other system therapy as firt line therapy after diagnose for primary HCC, ablation or system therapy as first line therapy for recurrent HCC.
Serious medical comorbidities.
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.

Sites / Locations

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

HAIC plus Bevacizumab and Toripalimab

Arm Description

Hepatic arterial infusion of oxaliplatin , fluorouracil, and leucovorin every 6 weeks. Lenvatinib 12 mg (or 8 mg) once daily (QD) oral dosing. Toripalimab, 240 mg intravenously every 3 weeks. Bevacizumab 15 mg/kg intravenously every 3 weeks.

Outcomes

Primary Outcome Measures

Progression free survival rate at 6 months

Progression was defined as progressive disease by independent radiologic review according to mRECIST or death from any cause

Secondary Outcome Measures

Overall survival (OS)

OS is the length of time from the date of randomization until death from any cause.

Progression free survival (PFS)

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)

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

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.

Full Information

NCT ID

NCT04627363

First Posted

November 12, 2020

Last Updated

November 12, 2020

Sponsor

Sun Yat-sen University

Collaborators

Second Affiliated Hospital of Guangzhou Medical University

1. Study Identification

Unique Protocol Identification Number

NCT04627363

Brief Title

HAIC Combined With Bevacizumab and Toripalimab for Advanced Hepatocellular Carcinama

Official Title

HAIC Synchronously Combined With Bevacizumab and Toripalimab First-line for Advanced Hepatocellular Carcinama

Study Type

Interventional

2. Study Status

Record Verification Date

November 2020

Overall Recruitment Status

Unknown status

Study Start Date

January 1, 2021 (Anticipated)

Primary Completion Date

June 30, 2022 (Anticipated)

Study Completion Date

June 30, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Sun Yat-sen University

Collaborators

Second Affiliated Hospital of Guangzhou Medical University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This is an open-label, single-arm clinical study to preliminarily observe and evaluate the efficacy and safety of hepatic arterial infusion chemotherapy of oxaliplatin, 5-fluorouracil and leucovorin synchronous combined with Bevacizumab and Toripalimab as the first-line therapy for advanced HCC.

Detailed Description

Hepatic arterial infusion chemotherapy (HAIC) of oxaliplatin, 5-fluorouracil and leucovorin was effective and safe for hepatocellular carcinoma. Bevacizumab, an angiogenesis Inhibitors was effectively used for hepatocelluar carcinama (HCC) therapy. Toripalimab, an programmed cell death protein-1 (PD-1) antibody, was effective and tolerable in patients with hepatocellular carcinoma and portal vein tumor thrombus. No study has evaluated HAIC plus Bevacizumab and Toripalimab. Thus, the investigators carried out this prospective, single-arm study to find out it.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hepatocellular Carcinoma, Bevacizumab, Liver Neoplasms, Toripalimab, Oxaliplatin

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

HAIC plus Bevacizumab and Toripalimab

Arm Type

Experimental

Arm Description

Intervention Type

Procedure

Intervention Name(s)

Hepatic arterial infusion chemotherapy

Intervention Description

administration of oxaliplatin , fluorouracil, and leucovorin via the tumor feeding arteries every 6 weeks

Intervention Type

Drug

Intervention Name(s)

Bevacizumab

Intervention Description

15mg/kg intravenously every 3 weeks

Intervention Type

Drug

Intervention Name(s)

Toripalimab

Intervention Description

240mg intravenously every 3 weeks

Primary Outcome Measure Information:

Title

Progression free survival rate at 6 months

Description

Progression was defined as progressive disease by independent radiologic review according to mRECIST or death from any cause

Time Frame

6 months]

Secondary Outcome Measure Information:

Title

Overall survival (OS)

Description

OS is the length of time from the date of randomization until death from any cause.

Time Frame

6 months

Title

Progression free survival (PFS)

Description

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.

Time Frame

6 months

Title

Objective response rate (ORR)

Description

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.

Time Frame

6 months

Title

Adverse events

Description

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.

Time Frame

6 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: HCC diagnosed by histopathological examination or Guidelines for Diagnosis and Treatment of Primary Liver Cancer or the recurrent HCC after surgery; age between 18 and 75 years; Stage B (middle stage) or C (late stage) HCC determined in accordance with Barcelona Clinic Liver Cancer staging system (BCLC stage). In case of stage B. No previous use of any systemic therapy or recurrent HCC. Child-Pugh class A or B; Eastern Cooperative Group performance status (ECOG) score of 0-2; 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 Prothrombin time ≤18s or international normalized ratio < 1.7. Ability to understand the protocol and to agree to and sign a written informed consent document. Exclusion Criteria: Cholangiocellular carcinoma (ICC); Patients with cancer thrombus in the main trunk of portal vein (Vp4), or cancer thrombus in inferior vena cava should be excluded; Accepting ablation or surgery or other system therapy as firt line therapy after diagnose for primary HCC, ablation or system therapy as first line therapy for recurrent HCC. Serious medical comorbidities. 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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Qunfnag Zhou, MD

Phone

86 19868000115

zhouqun988509@163.com

First Name & Middle Initial & Last Name or Official Title & Degree

Fei Gao, Professor

gaof@sysucc.org.cn

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Fei Gao

Organizational Affiliation

Sun Yat-sen University

Official's Role

Study Director

First Name & Middle Initial & Last Name & Degree

Kangshun Zhu, Professor

Organizational Affiliation

Second Affiliated Hospital of Guangzhou Medical University

Official's Role

Study Director

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

HAIC Combined With Bevacizumab and Toripalimab for Advanced Hepatocellular Carcinama

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