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

Study Overview
=================
Brief Summary
-----------------
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.

Official Title
-----------------
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

Conditions
-----------------
Hepatocellular Carcinoma (HCC)

Intervention / Treatment
-----------------
* Drug: Camrelizumab
* Drug: Rivoceranib (Apatinib)


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Camrelizumab Combined with Rivoceranib (Apatinib) Versus Active Surveillance
Masking: None (Open Label)


Arms and Interventions

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

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 |