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DEB-TACE+HAIC vs. HAIC for Large HCC

Primary Purpose

Unresectable Hepatocellular Carcinoma

Status

Recruiting

Phase

Phase 3

Locations

China

Study Type

Interventional

Intervention

dTACE-HAIC

HAIC

dTACE-HAIC protocol

HAIC protocol

About this trial

This is an interventional treatment trial for Unresectable Hepatocellular Carcinoma focused on measuring Hepatocellular Carcinoma, Transarterial chemoembolization, Hepatic arterial infusion chemotherapy

Eligibility Criteria

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

Inclusion Criteria:

Patients with HCC confirmed by histology/cytology or diagnosed clinically.
The maximum HCC lesion > 7 cm.
Unresectable HCC evaluated by the surgeon team.
At least one measurable intrahepatic target lesion.
Patients without cirrhosis, or with cirrhosis but the liver function of Child-Pugh Class A.
ECOG score of performance status ≤ 1 point.
Adequate organ and bone marrow function; the blood biochemical examination: platelet count ≥75×10^9/L, leukocyte >3.0×10^9/L, ASL and AST≤5×ULN, creatinine≤1.5×ULN, INR<1.5 or PT/APTT normal range.
Life expectancy of at least 3 months.

Exclusion Criteria:

Accompanied with tumor thrombus involving the main portal vein or bilateral first-order branch of portal vein.
Accompanied with vena cava tumor thrombus.
Extrahepatic metastasis.
Previous treatment with TACE, HAIC, liver transplantation, resection, ablation, radiotherapy, or systemic therapy.
Decompensated liver function, including: ascites, bleeding from gastroesophageal varices, and hepatic encephalopathy.
Those with organs (heart and kidneys) dysfunction who cannot tolerate TACE or HAIC treatment.
History of other malignancies.
Uncontrollable infection.
History of HIV.
Allergic to the drugs involved in the research.
Patients with gastrointestinal bleeding within 30 days, or other bleeding> CTCAE grade 3.
History of organ or cells transplantation.
Those with bleeding tendency.

Sites / Locations

the Second Affiliated Hospital of Guangzhou Medical UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Transarterial chemoembolization with drug-eluting beads plus hepatic arterial infusion chemotherapy

Hepatic arterial infusion chemotherapy

Arm Description

Patients will receive the combination treatment of DEB-TACE and HAIC.

Patients will receive HAIC treatment alone.

Outcomes

Primary Outcome Measures

Overall survival (OS)

The time from date of randomization to death due to any cause.

Secondary Outcome Measures

Objective response rate (ORR) per mRECIST.

The proportion of patients with the best response of complete response (CR) or partial response (PR) according to mRECIST.

ORR per RECIST 1.1.

The proportion of patients with the best response of CR or PR according to RECIST 1.1.

Disease control rate (DCR) per mRECIST.

The proportion of patients with the best response of CR, PR, or stable disease (SD) according to mRECIST.

DCR per RECIST 1.1.

The proportion of patients with the best response of CR, PR, or SD according to RECIST 1.1.

Progression free survival (PFS) per mRECIST.

The time from date of randomization until the first occurrence of disease progression (according to mRECIST) or death due to any cause, whichever occurs first.

Progression free survival (PFS) per RECIST 1.1.

The time from date of randomization until the first occurrence of disease progression (according to RECIST 1.1) or death due to any cause, whichever occurs first.

Success rate of conversion to resection

The proportion of patients with initially unresectable large HCC who were evaluated by the surgical team as suitable for surgical resection after dTACE-HAIC or HAIC treatment.

Adverse Events (AEs)

Number of patients with AEs assessed by Common Terminology Criteria for Adverse Events v5.0.

Full Information

NCT ID

NCT05263219

First Posted

February 12, 2022

Last Updated

June 19, 2023

Sponsor

Second Affiliated Hospital of Guangzhou Medical University

Collaborators

Hainan General Hospital, Maoming People's Hospital, Zhongshan People's Hospital, Guangdong, China, Affiliated Hospital of Guangdong Medical University, First People's Hospital of Foshan, Jiangmen Central Hospital, First Affiliated Hospital, Sun Yat-Sen University

1. Study Identification

Unique Protocol Identification Number

NCT05263219

Brief Title

DEB-TACE+HAIC vs. HAIC for Large HCC

Official Title

Transarterial Chemoembolization With Drug-eluting Beads Plus Hepatic Arterial Infusion Chemotherapy Versus Hepatic Arterial Infusion Chemotherapy Alone for Large Hepatocellular Carcinoma

Study Type

Interventional

2. Study Status

Record Verification Date

June 2023

Overall Recruitment Status

Recruiting

Study Start Date

February 10, 2022 (Actual)

Primary Completion Date

February 9, 2026 (Anticipated)

Study Completion Date

February 9, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Second Affiliated Hospital of Guangzhou Medical University

Collaborators

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

This study is conducted to evaluate the efficacy and safety of transarterial chemoembolization with drug-eluting beads (DEB-TACE) plus hepatic artery infusion chemotherapy (HAIC) compared with HAIC alone for unresectable large hepatocellular carcinoma (HCC).

Detailed Description

This is a multicenter, prospective and randomized study to evaluate the efficacy and safety of DEB-TACE (with CalliSpheres) plus HAIC compared with HAIC alone for unresectable large HCC (>7cm). 230 patients with initially unresectable large HCC (> 7cm) will be enrolled in this study. The patients will receive either DEB-TACE plus HAIC (dTACE-HAIC) or HAIC as the primary treatment using an 1:1 randomization scheme. In the dTACE-HAIC arm, the microcatheter will be reserved at the proper/left/right hepatic artery and chemotherapy drugs (FOLFOX-based regimen) will be intra-arterially administered though the microcatheter. The treatment can be repeated on demand (at a 4-6-week interval usually) based on the evaluation of follow-up laboratory and imaging examination by the multidisciplinary team. In the HAIC arm, treatment will repeated once every 3 weeks for up to six cycles. During follow-up, the potential resectability of the tumor will be assessed by the multidisciplinary team (MDT). Once the tumors become resectable, curative surgical resection will be recommended for the patients. The primary end point of this study is overall survival (OS). The secondary endpoints are tumor response (objective response rate and disease control rate), success rate of conversion to resection, progression-free survival (PFS), and adverse events (AEs).

6. Conditions and Keywords

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

Unresectable Hepatocellular Carcinoma

Keywords

Hepatocellular Carcinoma, Transarterial chemoembolization, Hepatic arterial infusion chemotherapy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

230 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Transarterial chemoembolization with drug-eluting beads plus hepatic arterial infusion chemotherapy

Arm Type

Experimental

Arm Description

Patients will receive the combination treatment of DEB-TACE and HAIC.

Arm Title

Hepatic arterial infusion chemotherapy

Arm Type

Active Comparator

Arm Description

Patients will receive HAIC treatment alone.

Intervention Type

Procedure

Intervention Name(s)

dTACE-HAIC

Intervention Description

For DEB-TACE, superselective catheterization is performed and CalliSpheres loaded with pirarubicin is use for chemoembolization. The embolization end point was blood stasis of the tumor-feeding arteries. In patients with huge or bilobar multiple lesions, in order to reduce the risk of complications, the embolization end point was not achieved in the initial TACE but in the second or third TACE session. After each chemoembolization, the microcatheter is reserved at the proper/left/right hepatic artery. The FOLFOX-based regimen is intra-arterially administered. During follow-up, the treatment will be repeated on demand (at a 4-6-week interval usually) based on the evaluation of the follow-up laboratory and imaging examination.

Intervention Type

Procedure

Intervention Name(s)

HAIC

Intervention Description

HAIC treatment is divided into 3-week cycles. The microcatheter is advanced into the proper/left/right hepatic artery on day 1 in every cycle of treatment. After the patient returned to the ward, the FOLFOX-based regimen is intra-arterially administered though the microcatheter. The treatment is repeated once every 3 weeks for up to six cycles.

Intervention Type

Drug

Intervention Name(s)

dTACE-HAIC protocol

Other Intervention Name(s)

Drugs for DEB-TACE and HAIC

Intervention Description

CalliSpheres (100-300 µm) loaded with pirarubicin for transarterial chemombolization: Typically, one vial of the beads was loaded with 60 mg pirarubicin. If blushed tumors is still visible after the embolization with one vial of beads, regular microspheres (8spheres) with diameters of 100-700 μm are additionally injected. FOLFOX-based regimen for hepatic arterial infusion chemotherapy: oxaliplatin, 85 mg/m2 infusion for 2 hours; leucovorin, 400 mg/m2 infusion for 2 hours; and 5-FU, 400 mg/m2 bolus infusion and then 2400 mg/m2 continuous infusion over 46 h.

Intervention Type

Drug

Intervention Name(s)

HAIC protocol

Other Intervention Name(s)

Drugs for HAIC

Intervention Description

FOLFOX-based regimen for hepatic arterial infusion chemotherapy: oxaliplatin, 85 mg/m2 infusion for 2 hours; leucovorin, 400 mg/m2 infusion for 2 hours; and 5-FU, 400 mg/m2 bolus infusion and then 2400 mg/m2 continuous infusion over 46 h.

Primary Outcome Measure Information:

Title

Overall survival (OS)

Description

The time from date of randomization to death due to any cause.

Time Frame

4 years.

Secondary Outcome Measure Information:

Title

Objective response rate (ORR) per mRECIST.

Description

The proportion of patients with the best response of complete response (CR) or partial response (PR) according to mRECIST.

Time Frame

4 years.

Title

ORR per RECIST 1.1.

Description

The proportion of patients with the best response of CR or PR according to RECIST 1.1.

Time Frame

4 years.

Title

Disease control rate (DCR) per mRECIST.

Description

The proportion of patients with the best response of CR, PR, or stable disease (SD) according to mRECIST.

Time Frame

4 years.

Title

DCR per RECIST 1.1.

Description

The proportion of patients with the best response of CR, PR, or SD according to RECIST 1.1.

Time Frame

4 years.

Title

Progression free survival (PFS) per mRECIST.

Description

The time from date of randomization until the first occurrence of disease progression (according to mRECIST) or death due to any cause, whichever occurs first.

Time Frame

4 years.

Title

Progression free survival (PFS) per RECIST 1.1.

Description

The time from date of randomization until the first occurrence of disease progression (according to RECIST 1.1) or death due to any cause, whichever occurs first.

Time Frame

4 years.

Title

Success rate of conversion to resection

Description

The proportion of patients with initially unresectable large HCC who were evaluated by the surgical team as suitable for surgical resection after dTACE-HAIC or HAIC treatment.

Time Frame

4 years.

Title

Adverse Events (AEs)

Description

Number of patients with AEs assessed by Common Terminology Criteria for Adverse Events v5.0.

Time Frame

4 years.

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: Patients with HCC confirmed by histology/cytology or diagnosed clinically. The maximum HCC lesion > 7 cm. Unresectable HCC evaluated by the surgeon team. At least one measurable intrahepatic target lesion. Patients without cirrhosis, or with cirrhosis but the liver function of Child-Pugh Class A. ECOG score of performance status ≤ 1 point. Adequate organ and bone marrow function; the blood biochemical examination: platelet count ≥75×10^9/L, leukocyte >3.0×10^9/L, ASL and AST≤5×ULN, creatinine≤1.5×ULN, INR<1.5 or PT/APTT normal range. Life expectancy of at least 3 months. Exclusion Criteria: Accompanied with tumor thrombus involving the main portal vein or bilateral first-order branch of portal vein. Accompanied with vena cava tumor thrombus. Extrahepatic metastasis. Previous treatment with TACE, HAIC, liver transplantation, resection, ablation, radiotherapy, or systemic therapy. Decompensated liver function, including: ascites, bleeding from gastroesophageal varices, and hepatic encephalopathy. Those with organs (heart and kidneys) dysfunction who cannot tolerate TACE or HAIC treatment. History of other malignancies. Uncontrollable infection. History of HIV. Allergic to the drugs involved in the research. Patients with gastrointestinal bleeding within 30 days, or other bleeding> CTCAE grade 3. History of organ or cells transplantation. Those with bleeding tendency.

Central Contact Person:

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

Mingyue Cai, Dr.

Phone

+86-20-34156205

cai020@yeah.net

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

Kangshun Zhu, Dr.

Phone

+86-20-34156205

zhksh010@163.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Kangshun Zhu, Dr.

Organizational Affiliation

Second Affiliated Hospital of Guangzhou Medical University

Official's Role

Study Chair

Facility Information:

Facility Name

the Second Affiliated Hospital of Guangzhou Medical University

City

Guangzhou

State/Province

Guangdong

ZIP/Postal Code

510260

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Mingyue Cai, Dr.

Phone

+86-20-34156205

cai020@yeah.net

12. IPD Sharing Statement

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DEB-TACE+HAIC vs. HAIC for Large HCC

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