Camrelizumab Combined With Apatinib Mesylate and TACE in the Perioperative Treatment of Hepatocellular Carcinoma

Camrelizumab Combined With Apatinib Mesylate and TACE in the Perioperative Treatment of Hepatocellular Carcinoma: a Randomized, Open-label, Parallel, Multicenter Trial

Hepatocellular carcinoma (HCC) is the most common primary liver cancer. Hepatectomy is a curable and effective method. However, the recurrence rate is as high as 50%~70% in 5 years after surgery. Perioperative treatment with immunotherapy combined with target therapy is expected to improve the patient's prognosis. This study aims to evaluate the efficacy, safety and tolerability of camrelizumab combined with apatinib mesylate in the perioperative period of resectable hepatocellular carcinoma. The primary purpose of this study is to evaluate 2 year event-free survival（2y-EFS） of camrelizumab combined with apatinib mesylate in the perioperative period of hepatocellular carcinoma (CNLC Ib-IIIa). The secondary research purpose is to evaluate the R0 resection rate, the rate of subjects with major pathological response, the rate of subjects with pathological complete response, event-free survival (EFS) and overall survival of camrelizumab combined with apatinib mesylate in the perioperative period of resectable hepatocellular carcinoma. The safety and tolerability is also evaluated.

Study Overview

• Status: Recruiting
• Conditions: Hepatocellular Carcinoma; Immunotherapy; Preoperative
• Intervention / Treatment: Drug: Camrelizumab; Drug: Apatinib Mesylate; Procedure: Radical surgery; Procedure: Preoperative TACE treatment; Drug: Camrelizumab; Drug: Apatinib Mesylate

Detailed Description

Hepatocellular carcinoma (HCC) is the most common primary liver cancer. Hepatectomy is a curable and effective method. However, the recurrence rate is as high as 50%~70% in 5 years after surgery. Perioperative treatment with immunotherapy combined with target therapy is expected to improve the patient's prognosis. This study aims to evaluate the efficacy, safety and tolerability of camrelizumab combined with apatinib mesylate in the perioperative period of resectable hepatocellular carcinoma. This trial includes subjects with CNLC Ib/IIa/IIb/IIIa HCC. All eligible subjects will be randomized (1:1) to experimental group or control group. In the experimental group, patients will be treated with following: neoadjuvant therapy ( perioperative TACE treatment，camrelizumab and apatinib, 2 cycles), radical surgery, adjuvant therapy (camrelizumab and apatinib, 6 cycles); in the control group, patients will be treated with following: radical surgery,adjuvant therapy (camrelizumab and apatinib, 6 cycles). The primary purpose of this study is to evaluate 2 year event-free survival（2y-EFS） of camrelizumab combined with apatinib mesylate in the perioperative period of hepatocellular carcinoma (CNLC Ib-IIIa). The secondary research purpose is to evaluate the R0 resection rate, the rate of subjects with major pathological response, the rate of subjects with pathological complete response, event-free survival (EFS) and overall survival of camrelizumab combined with apatinib mesylate in the perioperative period of resectable hepatocellular carcinoma. The safety and tolerability is also evaluated.

• Study Type: Interventional
• Enrollment (Estimated): 130
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Xuehao Wang, professor; Phone Number: 86-025-68303211; Email: Wangxh@njmu.edu.cn

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210029
      • Recruiting
      • Jiangsu Province Hospital
      • Contact: Xuehao Wang; Phone Number: 86-025-68303211; Email: wangxh@njmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Volunteer to participate in this study and sign an informed consent form.
• Age ≥18 years old, no gender limit.
• Hepatocellular carcinoma confirmed by histopathology, cytology or imaging.
• CNLC stage Ib (single tumor with diameter ≥8 cm)/IIa/IIb/IIIa hepatocellular carcinoma, except for CNLC IIIa hepatocellular carcinoma combined with main portal vein tumor thrombus；multiple hepatocellular carcinoma was allowed to be treated with surgical excision combined with intraoperative ablation.
• Child-Pugh score: A grade (≤6 points).
• ECOG PS score: 0-1 points.

Exclusion Criteria:

• Known intrahepatic cholangiocarcinoma, sarcomatoid HCC, mixed cell carcinoma and fibrolamellar cell carcinoma; have other active malignancies other than HCC within 5 years or at the same time.
• Currently accompanied by interstitial pneumonia or interstitial lung disease.
• Existence of active autoimmune disease or history of autoimmune disease and may relapse.
• Patients with active infection, unexplained fever ≥38.5℃ within 1 week before randomization, or baseline white blood cell count >15*10^9/L.
• Patients with congenital or acquired immune deficiencies (such as HIV-infected persons).
• Those who are known to be allergic to any monoclonal antibodies, anti-angiogenesis targeted drugs or excipients.

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental group; Preoperative TACE treatment → preoperative camrelizumab combined with apatinib mesylate (q2w, 2 cycles) → radical surgery → sequential camrelizumab and apatinib mesylate (q3w, at least 6 cycles)	Drug: Camrelizumab; Camrelizumab is administered at 200mg, q2w (2cycles) before radical surgery and 200mg, q3w (at least 6 cycles) after radical surgery; Drug: Apatinib Mesylate; Apatinib Mesylate is administered at 250mg, qd (2 cycles) before radical surgery and 250mg, qd (at least 6 cycles) after radical surgery; Procedure: Radical surgery; Radical surgery; Procedure: Preoperative TACE treatment; TACE treatment before preoperative camrelizumab combined with apatinib mesylate; Drug: Camrelizumab; Camrelizumab is administered at 200mg, q3w (at least 6 cycles) after radical surgery; Drug: Apatinib Mesylate; Apatinib Mesylate is administered at 250mg, qd (at least 6 cycles) after radical surgery
Active Comparator: Control group; Radical surgery → sequential camrelizumab and apatinib mesylate (q3w, at least 6 cycles)	Drug: Camrelizumab; Camrelizumab is administered at 200mg, q2w (2cycles) before radical surgery and 200mg, q3w (at least 6 cycles) after radical surgery; Drug: Apatinib Mesylate; Apatinib Mesylate is administered at 250mg, qd (2 cycles) before radical surgery and 250mg, qd (at least 6 cycles) after radical surgery; Procedure: Radical surgery; Radical surgery; Drug: Camrelizumab; Camrelizumab is administered at 200mg, q3w (at least 6 cycles) after radical surgery; Drug: Apatinib Mesylate; Apatinib Mesylate is administered at 250mg, qd (at least 6 cycles) after radical surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
2 year event-free survival（2y-EFS）	2y-EFS is defined as time from randomization to any of the following events: progression of disease that precludes surgery, local or distant recurrence, or death due to any cause.	2-year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	OS is defined as the time from randomisation to death.	3-year
Event-free survival (EFS)	EFS is defined as the time from randomisation to tumor progression, postoperative relaspse or metastasis, or death, which occur first.	3-year
R0 resection rate	R0 resection rate	30-day
The rate of subjects of major pathological response (MPR)	MPR is defined as less than 10% residual tumor after neoadjuvant therapy of camrelizumab and apatinib therapy.	30-day
the rate of subjects with pathological complete response (pCR)	pCR is defined as no histologic evidence of malignancy or only the ingredients of carcinoma in situ was found in primary tumors.	30-day
Disease-free survival (DFS)	DFS is defined as the time from randomization until disease recurrence or death from any cause.	3-year
Adverse event (AE)	Adverse events (AEs) ; serious adverse events (SAEs); surgery related safety.	3-year

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital with Nanjing Medical University
• Collaborators: Jiangsu Hengrui Pharmaceutical Co., Ltd.
• Investigators: Study Chair: Xuehao Wang, professor, The First Affiliated Hospital with Nanjing Medical University; Study Director: Yongxiang Xia, The First Affiliated Hospital with Nanjing Medical Univer

Study record dates

Study Major Dates

• Study Start (Actual): January 31, 2023
• Primary Completion (Estimated): November 1, 2025
• Study Completion (Estimated): November 1, 2027

Study Registration Dates

• First Submitted: November 6, 2022
• First Submitted That Met QC Criteria: November 6, 2022
• First Posted (Actual): November 14, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 30, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Apatinib
• Other Study ID Numbers: 2022-SR-558

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