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

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

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

Study Overview

• Status: Recruiting
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Procedure: Thermal ablation; Drug: Toripalimab

• Study Type: Interventional
• Enrollment (Anticipated): 116
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Liangrong Shi, M.D.; Phone Number: +8613974886662; Email: shiliangrong@126.com

Study Locations

• China
  • Hunan
    • Changsha, Hunan, China, 410005
      • Recruiting
      • Xiangya Hospital, Central South University
      • Contact: Liangrong Shi, M.D.; Phone Number: 8613974886662; Email: shiliangr@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

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
Other: Arm A; Patients with recurrent hepatocellular carcinoma would be treated with curative-intent ablation alone.	Procedure: Thermal ablation; 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.; Other Names: Local treatment
Experimental: Arm B; Patients with recurrent hepatocellular carcinoma would be treated with curative-intent ablation and adjuvant immunotherapy with toripalimab.	Procedure: Thermal ablation; 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.; Other Names: Local treatment; Drug: Toripalimab; toripalimab treatment (240mg intravenously every 3 weeks) started on day 3 after ablation for six months; Other Names: Immunotherapy

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Xiangya Hospital of Central South University
• Investigators: Principal Investigator: Liangrong Shi, M.D., Xiangya Hospital of Central South University

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2020
• Primary Completion (Anticipated): July 31, 2023
• Study Completion (Anticipated): July 31, 2024

Study Registration Dates

• First Submitted: February 7, 2022
• First Submitted That Met QC Criteria: February 13, 2022
• First Posted (Actual): February 15, 2022

Study Record Updates

• Last Update Posted (Actual): February 15, 2022
• Last Update Submitted That Met QC Criteria: February 13, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: Immunotherapy; Toripalimab
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma, Hepatocellular
• Other Study ID Numbers: IRTOE

Drug and device information, study documents

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