A Study to Evaluate Camrelizumab Plus Rivoceranib (Apatinib) as Adjuvant Therapy in Patients With Hepatocellular Carcinoma (HCC) at High Risk of Recurrence After Curative Resection or Ablation

A Randomized, Open-Label, Multi-Center, Phase Ⅲ Clinical Study of Camrelizumab Plus Rivoceranib (Apatinib) as Adjuvant Therapy in Patients With Hepatocellular Carcinoma (HCC) at High Risk of Recurrence After Curative Resection or Ablation

A Trial to Evaluate the Efficacy and Safety of Camrelizumab Plus Rivoceranib (Apatinib) Versus Active Surveillance as Adjuvant Therapy in Patients with Hepatocellular Carcinoma (HCC) at High Risk of Recurrence After Curative Resection or Ablation.

Study Overview

• Status: Active, not recruiting
• Conditions: Hepatocellular Carcinoma (HCC)
• Intervention / Treatment: Drug: Camrelizumab; Drug: Rivoceranib (Apatinib)

• Study Type: Interventional
• Enrollment (Actual): 687
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Linna Wang, MD; Phone Number: 021-60453196; Email: linna.wang@hengrui.com
• Study Contact Backup: Name: Jing Wu, MD; Phone Number: 010-67166319; Email: jing.wu@hengrui.com

Study Locations

• China
  • Chongqing
    • Chongqing, Chongqing, China
      • The First Affiliated Hospital of Chongqing Medical University
  • Guangzhou
    • Nanjin, Guangzhou, China
      • Guangxi Medical University Affiliated Tumor Hospital
  • Guizhou
    • Guiyang, Guizhou, China
      • Guizhou Cancer Hospital
  • Shanghai
    • Shanghai, Shanghai, China
      • Renji Hospital, Shanghai Jiaotong University School of Medicine
    • Shanghai, Shanghai, China
      • Zhongshan Hospital, Fudan University
  • Tianjin
    • Tianjin, Tianjin, China
      • Tianjin Medical University Cancer Institute and Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Subjects with a histopathological diagnosis of HCC
• Subjects who have undergone a curative resection or ablation (radiofrequency ablation [RFA] or microwave ablation [MVA] only)
• 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 or ablation within 4 weeks prior to randomization
• High risk for HCC recurrence after resection or ablation
• For patients who received post-operative transarterial chemoembolization: full recovery from the procedure within 4 weeks prior to randomization
• Child-Pugh Class: Grade A
• ECOG-PS score: 0 or 1
• Subjects with HCV- RNA (+) must receive antiviral therapy
• Adequate organ function

Exclusion Criteria:

• Known hepatocholangiocarcinoma, sarcomatoid HCC, mixed cell carcinoma and fibrolamellar HCC; other active malignant tumor except HCC within 5 years or simultaneously
• Evidence of residual lesion, recurrence, and metastasis at randomization;
• Moderate-to-severe ascites with clinical symptoms
• History of hepatic encephalopathy
• History of gastrointestinal hemorrhage within 6 months prior to the start of study treatment or clear tendency of gastrointestinal haemorrhage
• Active or history of autoimmune disease
• Interstitial lung disease that is symptomatic or may interfere with the detection and management of suspected drug-related pulmonary toxicity
• Cardiac clinical symptom or cardiovascular disease that is not well controlled
• Severe infection within 4 weeks prior to the start of study treatment
• HIV infection
• 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
• Thrombosis or thromboembolic event within 6 months prior to the start of study treatment
• Known genetic or acquired hemorrhage or thrombotic tendency
• Abdominal fistula, gastrointestinal perforation or intraperitoneal abscess within 6 months prior to the start of study treatment
• Serious non-healing or dehiscing wound
• Major Curative procedure within four weeks
• Factors to affect oral administration
• Previous or current presence of metastasis to central nervous system

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment group (Camrelizumab Plus Rivoceranib (Apatinib)); Drug: Camrelizumab; Drug: Rivoceranib (Apatinib)	Drug: Camrelizumab; Subjects receive Camrelizumab intravenously, Dosage form: lyophilized powder; Drug: Rivoceranib (Apatinib); Subjects receive Rivoceranib (Apatinib) orally, Dosage form: tablet
No Intervention: Control group (Active surveillance)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrence-Free Survival (RFS), as Determined by the blinded independent review committee (BIRC)	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 approximately 43 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
RFS Rate at 24 and 36 Months, as Assessed by the Investigator		Randomization up to 24 months and up to 36 months
Time to Recurrence (TTR) as determined by the investigator and by BIRC	TTR defined as the time from randomization to first documented occurrence of local, regional, or metastatic HCC	Randomization up to approximately 43 months
Overall Survival (OS)	OS is defined as the time from randomization to death from any cause	Randomization up to approximately 43 months
The incidence and severity of adverse events (AEs) and serious adverse events (SAEs) as assessed by CTCAE v5.0		Baseline up to approximately 43 months

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2021
• Primary Completion (Anticipated): July 31, 2024
• Study Completion (Anticipated): July 31, 2024

Study Registration Dates

• First Submitted: November 19, 2020
• First Submitted That Met QC Criteria: November 19, 2020
• First Posted (Actual): November 20, 2020

Study Record Updates

• Last Update Posted (Actual): April 25, 2023
• Last Update Submitted That Met QC Criteria: April 23, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Disease Attributes; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Recurrence; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Apatinib
• Other Study ID Numbers: SHR-1210-III-325

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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