Postoperative Adjuvant Sintilimab in Hepatocellular Carcinoma With Microvascular Invasion

Postoperative Adjuvant Sintilimab in Hepatocellular Carcinoma With Microvascular Invasion: A Multicenter, Phase III, Randomized Study

To compare the impact on recurrence risk of adjuvant Sintilimab (a recombinant fully human anti-PD-1 monoclonal antibody) for patients with hepatocellular carcinoma and microvascular invasion (MVI) after hepatectomy.

Study Overview

• Status: Not yet recruiting
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Drug: Sintilimab (9 cycles); Drug: Sintilimab (18 cycles); Other: Active surveillance

Detailed Description

This study is a prospective, multicenter, open-label, randomized controlled clinical trial, aiming to recruit 360 patients with MVI-positive HCC who have undergone surgical resection. The patients will be randomly divided into three groups: the first group will receive six months of adjuvant therapy with Sintilimab (200 mg every three weeks for a total of 9 cycles), the second group will receive one year of adjuvant therapy with Sintilimab (200 mg every three weeks for a total of 18 cycles), and the Active surveillance group will be closely followed postoperatively. A maximum of one postoperative adjuvant TACE is permitted.

• Study Type: Interventional
• Enrollment (Estimated): 360
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Xiaoping Chen, Prodessor; Phone Number: 02783665213; Email: chenxpchenxp@163.com

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Subjects with a histopathological diagnosis of HCC
• Undergone a curative resection
• Pathologically confirmed HCC with microvascular invasion (MVI)
• Aged 18-75 years
• No previous systematic treatment and locoregional therapy for HCC prior to randomization
• Absence of major macrovascular invasion
• No extrahepatic spread
• Full recovery from Curative resection within 4 weeks prior to randomization
• Child-Pugh: Grade A or B(7)
• ECOG-PS score: 0 or 1
• Subjects with HCV- RNA (+) must receive antiviral therapy
• Adequate organ function

Exclusion Criteria:

• Known fibrolamellar HCC, sarcomatoid HCC, mixed cholangiocarcinom or recurrent HCC
• Any preoperative treatment for HCC including local and systemic therapy
• Have received more than 1 cycle of adjuvant TACE following surgical resection
• Any acute active infectious diseases, active or history of autoimmune disease, or immune deficiency
• Known history of serious allergy to any monoclonal antibody or targeted anti-angiogenic drug
• Subjects with inadequately controlled hypertension or history of hypertensive crisis or hypertensive encephalopathy
• Cardiac clinical symptom or cardiovascular disease that is not well controlled
• Thrombosis or thromboembolic event within 6 months prior to the start of study treatment
• Any persistent serious surgery-related complications; esophageal and/or gastric variceal bleeding within 6 months
• Abdominal fistula, gastrointestinal perforation or intraperitoneal abscess within 6 months prior to the start of study treatment
• Inability or refusal to comply with the treatment and monitoring

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sintilimab for six months group (9 cycles); Patients receive Sintilimab at a dose of 200 mg via intravenous injection, with one cycle every three weeks, for a total of 9 cycles or until disease recurrence or intolerable adverse effects occurred.	Drug: Sintilimab (9 cycles); IV infusion of Sintilimab （200mg intravenously every 3 weeks for a total of 9 cycles）; Other Names: IBI 308
Experimental: Sintilimab for one year group (18 cycles); Patients receive Sintilimab at a dose of 200 mg via intravenous injection, with one cycle every three weeks, for a total of 18 cycles or until disease recurrence or intolerable adverse effects occurred.	Drug: Sintilimab (18 cycles); IV infusion of Sintilimab （200mg intravenously every 3 weeks for a total of 18 cycles）; Other Names: IBI 308
Active Comparator: Active surveillance; Patients are closely monitored postoperatively.	Other: Active surveillance; Active surveillance

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrence-Free Survival (RFS)	RFS is defined as the time from randomization to the first documented occurrence of local, regional, or metastatic HCC as determined by BIRC, or death from any cause (whichever occurs first).	Randomization up to 60 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	OS is defined as the time from randomization to death from any cause	Randomization up to 60 months
Adverse events	The incidence and severity of adverse events (AEs) and serious adverse events (SAEs) as assessed by CTCAE v5.0	Baseline up to 60 months
RFS Rate at 12 ,24 , 36 , 60 Months	RFS is defined as the time from randomization to the first documented occurrence of local, regional, or metastatic HCC as determined by BIRC, or death from any cause (whichever occurs first).	Randomization up to 60 months
Quality of Life (QoL) Scale Score	Change from Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) and Hepatocellular Carcinoma Module (EORTC QLQ-HCC18) Scale Score	Baseline up to 60 months

Collaborators and Investigators

• Sponsor: Tongji Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2024
• Primary Completion (Estimated): June 30, 2025
• Study Completion (Estimated): November 30, 2026

Study Registration Dates

• First Submitted: October 13, 2023
• First Submitted That Met QC Criteria: October 17, 2023
• First Posted (Actual): October 18, 2023

Study Record Updates

• Last Update Posted (Actual): April 30, 2024
• Last Update Submitted That Met QC Criteria: April 28, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Hepatocellular Carcinoma; Immunotherapy; Checkpoint Inhibitor; Programmed Cell Death 1; Adjuvant; Microvascular Invasion
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular
• Other Study ID Numbers: Adjuvant-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No