Adjuvant Immunotherapy With Toripalimab Following Curative-intent Ablation for Recurrent Hepatocarcinoma

Study Overview
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Brief Summary
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This phase II study is to evaluate the efficacy of the adjuvant immunotherapy after curative-intent ablation for recurrent hepatocarcinoma

Official Title
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A Randomized Phase II Study of Adjuvant Immunotherapy With Toripalimab Following Curative-intent Ablation for Recurrent Hepatocarcinoma

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: Toripalimab
* Procedure: Thermal ablation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HCC diagnosed as (i) the presence of risk factors including hepatitis B or C virus and liver cirrhosis, a serum a-fetoprotein (AFP) level greater than 200 IU/ml and a radiologically compatible feature with HCC in one or more CT/MRI/angiograms, or (ii) the presence of risk factors including hepatitis B or C virus and liver cirrhosis, a serum a-fetoprotein (AFP) level less than 200 IU/ml, and a radiologically compatible feature with HCC in two or more CT/MRI/angiograms or (iii) histological confirmation. HCC patients who had recurrent or residual tumor after other treatments without evidence of extrahepatic metastasis the largest diameter of tumor should be less than 3cm, and the number of tumor ≤2 no previous treatment to target tumors by other forms of RT. liver function of Child-Pugh class A or B7 (Child-Pugh score of ≤7). performance status of 0 to 2 on the Eastern Cooperative Oncology Group (ECOG) score. WBC count ≥ 2,000/mm3; hemoglobin level ≥ 7.5 g/dL; platelet count ≥ 50,000/mm3; and adequate hepatic function (total bilirubin ≤ 3.0 mg/dL; AST and ALT < 5.0× upper limit of normal; no ascites). no serious comorbidities other than liver cirrhosis. written informed consent. Exclusion Criteria: HCC diagnosed as (i) the presence of risk factors including hepatitis B or C virus and liver cirrhosis, a serum a-fetoprotein (AFP) level greater than 200 IU/ml and a radiologically compatible feature with HCC in one or more CT/MRI/angiograms, or (ii) the presence of risk factors including hepatitis B or C virus and liver cirrhosis, a serum a-fetoprotein (AFP) level less than 200 IU/ml, and a radiologically compatible feature with HCC in two or more CT/MRI/angiograms or (iii) histological confirmation. HCC patients who had recurrent or residual tumor after other treatments without evidence of extrahepatic metastasis the largest diameter of tumor should be less than 3cm, and the number of tumor ≤2 no previous treatment to target tumors by other forms of RT. Liver function of Child-Pugh class A or B7 (Child-Pugh score of ≤7). Performance status of 0 to 2 on the Eastern Cooperative Oncology Group (ECOG) score. WBC count ≥ 2,000/mm3; hemoglobin level ≥ 7.5 g/dL; platelet count ≥ 50,000/mm3; and adequate hepatic function (total bilirubin ≤ 3.0 mg/dL; AST and ALT < 5.0× upper limit. Written informed consent. Exlusion criteria: Evidence of extrahepatic metastasis. Liver function of Child-Pugh class B8-9 and C (Child-Pugh score of >7). Previous history of other forms of RT adjacent to target tumors. Poor performance status of 3 to 4 on the Eastern Cooperative Oncology Group (ECOG) score. Pregnant or breast feeding status. Previous history uncontrolled other malignancies within 2 years.

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 |
| --- | --- |
| Other: Arm A<br>Patients with recurrent hepatocellular carcinoma would be treated with curative-intent ablation alone. | Procedure: Thermal ablation<br>* The ablation operation was performed under local or compound anesthesia and guided by ultrasonography (US) or computed tomography (CT). To ensure complete destruction of the tumor, the ablation area must exceed the tumor boundary 1.0 cm.<br>* Other names: Local treatment;|
| Experimental: Arm B<br>Patients with recurrent hepatocellular carcinoma would be treated with curative-intent ablation and adjuvant immunotherapy with toripalimab. | Drug: Toripalimab<br>* toripalimab treatment (240mg intravenously every 3 weeks) started on day 3 after ablation for six months<br>* Other names: Immunotherapy;Procedure: Thermal ablation<br>* The ablation operation was performed under local or compound anesthesia and guided by ultrasonography (US) or computed tomography (CT). To ensure complete destruction of the tumor, the ablation area must exceed the tumor boundary 1.0 cm.<br>* Other names: Local treatment;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-free survival | Disease-free survival was defined as the interval from the date of randomization to date of detection new recurrent disease | up to 3 years until study closed | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Overall survival (OS) was defined as the interval from the date of randomization to death or study closed | up to 3 years until study closed | 
| Number of participants with adverse events | Evaluation will be done using NCI-CTCAE (version 4.03). | Up to approximately 3 years | 
| Predictive Biomarkers | Tissue and blood biomarkers in including PD-L1 expression, tumor mutation burden defined as the number of non-inherited mutations per million bases of investigated genomic sequence | Up to approximately 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Toripalimab, Immunotherapy