Tislelizumab Combined With IMRT Neoadjuvant Treatment for Resectable Hepatocellular Carcinoma With PVTT

Tislelizumab Combined With Intensity Modulated Radiation Therapy（IMRT) Neoadjuvant Treatment for Resectable Hepatocellular Carcinoma With Portal Vein Tumor Thrombus

Due to the biological characteristics and liver anatomical characteristics of liver cancer, liver cancer cells easily invade the vascular system, especially the portal venous system, forming portal vein tumor thrombus (PVTT) , and its incidence is reported to be 44.0% ~ 62.2%. Once PVTT occurs in patients with liver cancer, the disease develops rapidly, and intrahepatic and extrahepatic metastasis, portal hypertension, jaundice, and abdominal effusion can occur in a short time with an average survival time of 2.7 months. PVTT is one of the major adverse factors for the prognosis of liver cancer and occupies an important weight influence in the clinical staging system of liver cancer. In some hepatocellular carcinoma (HCC) patients with PVTT and selective resectability, surgery versus non-surgery can lead to better survival of patients.

A retrospective analysis showed that neoadjuvant radiotherapy can reduce the extent of invasion of PVTT and improve postoperative survival in some HCC patients. Another prospective study showed that neoadjuvant radiotherapy could significantly improve the overall survival of resectable liver cancer with PVTT, and neoadjuvant radiotherapy could improve the 2-year survival of patients from 9.4% to 27.4% 27.4%, with an effective response of 20.7%.

This study is a prospective, single-center, single-arm study to assess the efficacy and safety of neoadjuvant therapy with tislelizumab combined with IMRT for resectable liver cancer with PVTT.

Study Overview

• Status: Not yet recruiting
• Conditions: Hepatocellular Carcinoma With Portal Vein Tumor Thrombus
• Intervention / Treatment: Drug: Tislelizumab; Radiation: IMRT

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Xinrong Yang; Phone Number: 86-13764295279; Email: yang.xinrong@zs-hospital.sh.cn

Study Locations

• China
  • Shanghai, China
    • Zhongshan Hospital, Fudan University
    • Principal Investigator: Jian Zhou
    • Contact: Xinrong Yang; Email: yang.xinrong@zs-hospital.sh.cn

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:

• Histologically or cytologically confirmed hepatocellular carcinoma
• Patients with at least one measurable lesion
• Resectable primary lesion, PVTTⅡ-Ⅲtype
• No previous treatment for hepatocellular carcinoma
• Eastern Cooperative Oncology Group(ECOG): Performance Status(PS)score 0-1
• Child-Pugh score A
• Expected survival ≥ 3 months
• Baseline blood routine and blood biochemical indicators should meet the following criteria:

hemoglobin ≥ 90 g/L, absolute neutrophil count ≥ 1.5 × 10 ^/L, platelet count ≥ 75 × 10 ^/L aspartate or alanine aminotransferase 5 times the upper limit of normal (ULN), alkaline phosphatase ≤ 2.5 times the ULN, serum albumin ≥ 30 g/L; serum creatinine 1.5 times the ULN; international normalized ratio (INR)) ≤ 2 or prothrombin time (PT) more than the upper limit of normal range ≤ 6 seconds

• Appropriate to participate in this trial as assessed by the investigator before entering the study
• Male and female subjects of childbearing potential must agree to use an effective method of contraception throughout the study
• Signed informed consent.

Exclusion Criteria:

• Imaging showed distant metastasis
• Previous treatment with other effective regimens (including surgery, radiotherapy, systemic therapy, etc.)
• Previous allergic reactions to the same kind of drugs
• Pregnant or lactating patients
• Active hepatitis B or C (hepatitis B: HBsAg positive and Hepatitis B (HBV )DNA ≥ 1*10^4 IU/ml; hepatitis C: hepatitis C virus (HCV) antibody and HCV RNA positive, requiring simultaneous antiviral therapy)
• Pericardial effusion, uncontrolled pleural effusion or clinically severe ascites at screening
• History of interstitial lung disease, pneumonitis, or uncontrolled systemic disease, including diabetes, hypertension, pulmonary fibrosis, acute lung disease
• Suffering from severe cardiovascular disease within 12 months before screening, such as symptomatic coronary heart disease,≥II congestive heart failure, uncontrolled arrhythmia, infarction, etc
• Any active immunodeficiency or autoimmune disease at screening and/or any history of immunodeficiency or autoimmune disease that may recur (such as hypothyroidism or hyperthyroidism, interstitial pneumonia, enteritis, hepatitis, hypophysitis, vasculitis, myocarditis, etc.)
• Use of steroids or other systemic immunosuppressive therapy 14 days before enrollment; use of steroids or other systemic immunosuppressive therapy
• Patients with other previous malignancies that are not cured; Patients with other previous malignancies that are not cured
• Immunocompromised patients, such as immunocompromised patients, such as human immunodeficiency virus (HIV) positive; positive
• With uncontrollable psychosis; With uncontrollable psychosis
• Other factors make the investigators think it is inappropriate to participate in this trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tislelizumab+IMRT	Drug: Tislelizumab; 200mg, Q3W; Radiation: IMRT; 4 Gy* 5 Fx,5Fx/Week

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relapse-free survival( RFS)	Defined as the time from the date of surgery to the date of disease recurrence or death whichever occur first	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	Defined as the time from the date of treatment start to the date of death or to the date of last follow-up for patients alive	Up to 2 years
Resection rate (R0 resection rate)	Defined as the proportion of patients undergoing radical resection to the total subjects (R0 resection rate)	Up to 2 years
Objective response rate (ORR) assessed by mRECIST	Defined as the proportion of patients who had a best overall tumor response rating of complete response (CR) or partial response (PR).	Up to 2 years
Adverse Events (AEs)	Defined as the proportion of patients with AE, treatment-related AE (TRAE), immune-related AE (irAE), serious adverse event (SAE), assessed by NCI CTCAE v5.0; Surgical safety including Intraoperative blood loss，PHLF assessed by ISGLS（2012），Postoperative complications evaluated by modified Clavien-Dindo system.	Up to 2 years

Collaborators and Investigators

• Sponsor: Shanghai Zhongshan Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): April 20, 2021
• Primary Completion (Anticipated): April 20, 2022
• Study Completion (Anticipated): December 20, 2023

Study Registration Dates

• First Submitted: April 12, 2021
• First Submitted That Met QC Criteria: April 19, 2021
• First Posted (Actual): April 20, 2021

Study Record Updates

• Last Update Posted (Actual): April 20, 2021
• Last Update Submitted That Met QC Criteria: April 19, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Cardiovascular Diseases; Vascular Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Embolism and Thrombosis; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Thrombosis
• Other Study ID Numbers: B2020-187R-1

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