Clinical trial NCT04850157: Tislelizumab Combined With IMRT Neoadjuvant Treatment for Resectable Hepatocellular Carcinoma With PVTT
Official title: Tislelizumab Combined With Intensity Modulated Radiation Therapy（IMRT) Neoadjuvant Treatment for Resectable Hepatocellular Carcinoma With Portal Vein Tumor Thrombus
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Hepatocellular Carcinoma With Portal Vein Tumor Thrombus
Lead sponsor: Shanghai Zhongshan Hospital
Sponsor class: OTHER
First posted: 2021-04-20
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Relapse-free survival( RFS)
timeFrame: Up to 2 years
Secondary outcomes:
measure: Resection rate (R0 resection rate)
timeFrame: Up to 2 years
measure: Objective response rate (ORR) assessed by mRECIST
timeFrame: Up to 2 years
measure: Overall survival (OS)
timeFrame: Up to 2 years
measure: Adverse Events (AEs)
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Zhongshan hospital, Fudan University
Study officials:
References: