A Study to Evaluate Sintilimab Plus Lenvatinib as Adjuvant Therapy in Hepatocellular Carcinoma With Portal Vein Tumor Thrombosis (PVTT) After Surgical Resection

Study Overview
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Brief Summary
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To compare the impact on recurrence risk of adjuvant Sintilimab (a recombinant fully human anti-PD-1 monoclonal antibody) plus Lenvatinib for patients with hepatocellular carcinoma and portal vein tumor thrombus (PVTT ) after hepatectomy.

Official Title
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A Phase III Trial of Sintilimab Plus Lenvatinib in Hepatocellular Carcinoma With Portal Vein Tumor Thrombosis (PVTT) After Surgical Resection

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: Sintilimab
* Drug: Lenvatinib
* Procedure: Transarterial Chemoembolization (TACE)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with a histopathological diagnosis of HCC Undergone a curative resection Pathologically confirmed HCC with portal vein tumor thrombus (PVTT) Aged 18-75 years No previous systematic treatment and locoregional therapy for HCC prior to randomization 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 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 Active or history of autoimmune disease 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sintilimab Plus Lenvatinib<br> | Drug: Sintilimab<br>* IV infusion of Sintilimab （200mg intravenously every 3 weeks for a total of 18 cycles or tumour recurrence）<br>* Other names: IBI 308;Drug: Lenvatinib<br>* 8mg orally once a day for 1 year<br>* Other names: LENVIMA;|
| Active Comparator: TACE(one cycle) + active surveillance<br> | Procedure: Transarterial Chemoembolization (TACE)<br>* One cycle of TACE postoperatively<br>|

What is the study measuring?
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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 approximately 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| RFS Rate at 12 and 24 Months |  | up to 24 months | 
| Overall Survival (OS) |  | Randomization up to approximately 36 months | 
| Adverse events (AEs) | The incidence and severity of adverse events (AEs) and serious adverse events (SAEs) as assessed by CTCAE v5.0 | Randomization up to approximately 36 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) Combined Global Health Status (GHS) / Quality of Life (QoL) Scale Score | Baseline up to 36 months | 
| Hepatocellular Carcinoma Module (EORTC QLQ-HCC18) Scale Score | The EORTC QLQ-HCC18 is an HCC-specific questionnaire, administered in addition to the EORTC QLQ-C30, with scores ranging from 0-100. Higher scores indicate more severe symptoms/problems. Change from baseline in the EORTC QLQ-HCC18 scale score will be reported | Baseline up to 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Programmed Cell Death 1, lysine kinase inhibitor, Immunotherapy, Adjuvant, Hepatocellular Carcinoma, Portal vein tumor thrombus,PVTT