Lenvatinib+Sintilimab+TACE vs. Lenvatinib+TACE for Advanced HCC

NCT ID: NCT05608200

Last Updated: 2023-05-31

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 427 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-11-02
• Study Completion Date: 2026-10-31

Brief Summary

This study is conducted to evaluate the efficacy and safety of lenvatinib, sintilimab plus TACE (Len-Sin-TACE) compared with lenvatinib plus TACE (Len-TACE) for patients with advanced hepatocellular carcinoma (HCC).

Detailed Description

This is a multicenter, prospective and randomized controlled trial to evaluate the efficacy and safety of Len-Sin-TACE versus Len-TACE for patient with advanced HCC.

427 patients with advanced HCC (CNLC IIIa-IIIb/BCLC C stage) will be enrolled in this study. The patients will receive either Len-Sin or Len alone after first TACE using an 2:1 randomization scheme. In the Len-Sin arm, lenvatinib 12mg (body weight ≥60kg) or 8mg (body weight <60kg) P.O. qd and sintilimab (200mg I.V. q3w) will be started at 3-7 days after the first TACE. In the the Len arm, lenvatinib 12mg (body weight ≥60kg) or 8mg (body weight <60kg) P.O. qd will be started at 3-7 days after the first TACE.

TACE will be repeated if clinically indicated based on the evaluation of follow-up laboratory and imaging examination. Lenvatinib will last until disease progresses, intolerable toxicity, withdrawal of informed consent, loss of follow-up, death, or other circumstances that require termination of treatment, whichever occurs first. Sintilimab will last up to 24 months, or until disease progresses, intolerable toxicity, withdrawal of informed consent, loss of follow-up, death, or other circumstances that require termination of treatment, whichever occurs first. In the Len-Sin arm, patients will be allowed to have lenvatinib or sintilimab as a sigle agent and will be still considered on study when the other drug cause intolerable toxicity.

The primary end point of this study is overall survival (OS). The secondary endpoints are progression-free survival (PFS), time to progression (TTP), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs).

Conditions

Hepatocellular Carcinoma Non-resectable

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Len-Sin-TACE

Lenvatinib, Sintilimab Plus TACE

Group Type: EXPERIMENTAL

Lenvatinib, sintilimab plus TACE

Intervention Type: DRUG

Lenvatinib 12mg (body weight ≥60kg) or 8mg (body weight \<60kg) P.O. qd and sintilimab (200mg I.V. q3w) will be started at 3-7 days after the first TACE. TACE will be repeated if clinically indicated. Treatment of sintilimab will last up to 24 months. Patients will be allowed to have lenvatilib or sintilimab as a sigle agent and will be still considered on study when the other drug cause intolerable toxicity.

Len-TACE

Lenvatinib Plus TACE

Group Type: ACTIVE_COMPARATOR

Lenvatinib plus TACE

Intervention Type: DRUG

Lenvatinib 12mg (body weight ≥60kg) or 8mg (body weight \<60kg) P.O. qd will be started at 3-7 days after the first TACE. TACE will be repeated if clinically indicated. The interruption, dose reduction and discontinuation of lenvatinib depended on the presence and severity of toxicities according to the drug directions.

Interventions

Lenvatinib, sintilimab plus TACE

Lenvatinib 12mg (body weight ≥60kg) or 8mg (body weight \<60kg) P.O. qd and sintilimab (200mg I.V. q3w) will be started at 3-7 days after the first TACE. TACE will be repeated if clinically indicated. Treatment of sintilimab will last up to 24 months. Patients will be allowed to have lenvatilib or sintilimab as a sigle agent and will be still considered on study when the other drug cause intolerable toxicity.

Intervention Type: DRUG

Lenvatinib plus TACE

Lenvatinib 12mg (body weight ≥60kg) or 8mg (body weight \<60kg) P.O. qd will be started at 3-7 days after the first TACE. TACE will be repeated if clinically indicated. The interruption, dose reduction and discontinuation of lenvatinib depended on the presence and severity of toxicities according to the drug directions.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Advanced HCC (BCLC stage C, or CNLC IIIa and IIIb ) with diagnosis confirmed by histology/cytology or clinically
• Patients who have Tumor recurrence after surgical resection or ablation are allowed to be included
• At least one measurable intrahepatic target lesion
• Child-Pugh class A/B
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Life expectancy of at least 3 months

Exclusion Criteria

• Obstructive portal vein tumor thrombus involving both the left and right portal vein or main portal vein without collateral vessels
• Vascular invasion involving inferior vena cava
• Central nervous system metastasis
• Patients who received prior systemic therapy, immunotherapy, TACE, transcatheter arterial radioembolization (TARE), transcatheter arterial embolization (TAE), hepatic arterial infusion chemotherapy (HAIC) or radiation therapy for HCC
• History of organ and cell transplantation
• History of bleeding from esophageal and gastric varices
• History of hepatic encephalopathy
• hematologic examination: white blood cell count <3.0×10^9/L, platelets <50×10^9/L
• Prothrombin time prolongation ≥ 4s
• Severe organ (heart, lung, kidney) dysfunction
• History of malignancy other than HCC
• Active hepatitis B or C infection; hepatitis B virus (HBV) DNA > 1000 copies/ml; hepatitis C virus (HCV) RNA > 1000 copies/ml. Those who possess the indicators lower than the above criteria after nucleotide antiviral treatment can be enrolled

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Second Affiliated Hospital of Guangzhou Medical University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kangshun Zhu, MD

Role: PRINCIPAL_INVESTIGATOR

Second Affiliated Hospital of Guangzhou Medical University

Locations

The Second Affiliated Hospital of Guangzhou Medical University

Guangzhou, Guangdong, China

Site Status: RECRUITING

Countries

China

Central Contacts

Mingyue Cai, MD

Role: CONTACT

cai020@yeah.net

+86-20-34156205

Facility Contacts

Kangshun Zhu, MD

Role: primary

zhksh010@126.com

+86-20-34156205

Other Identifiers

MIIR-10

Identifier Type: -

Identifier Source: org_study_id