Safety and Efficacy of Lenvatinib and Anti-PD1 Antibody Combined With Radiotherapy Neoadjuvant Treatment for Resectable Hepatocellular Carcinoma With PVTT

NCT05225116 | Unknown Phase 1

• 1 other identifier: 21323-0-03
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Patients with hepatocellular carcinoma with PVTT can benefit from surgical resection and radiotherapy. As the rapid development of systematic treatment in hepatocellular carcinoma, ICIs neoadjuvant therapy is being actively explored .But there is no evidence to prove the safety and efficacy of lenvatinib and anti-PD1 antibody combined with radiotherapy neoadjuvant treatment for resectable hepatocellular carcinoma with PVTT. This study intends to supplement the evidence of benefit in such patients.

Conditions

Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (2)

• Safety(CTCAE v5.0)

  Number of patients who reported incidence of grade ≥3 treatment related adverse events.

  up to 5 years

• Number of patients who complete pre-op treatment and proceed to surgery

  Number of patients who complete pre-op treatment and proceed to surgery

  up to 5 years

Secondary Outcomes (6)

• Major Pathological Response(MPR)

  Within 3 months after surgery

• Objective Response Rate(ORR)

  within 1 week before surgery

• Imaging-pathology Concordance Rate

  Within 3 months after surgery

• PVTT regression rate

  Within 3 months after surgery

• Median Overall survival(mOS)

  up to 5 years

Study Arms (1)

Sintilimab+Lenvatinib+Radiotherapy

EXPERIMENTAL

Drug: Sintilimab; Drug: Lenvatinib; Radiation: radiotherapy

Interventions

Sintilimab DRUG

Sintilimab will be at a dose of 200mg,Q3W

Sintilimab+Lenvatinib+Radiotherapy

Lenvatinib DRUG

On the first day of the trial, Lenvatinib will be taken orally once daily （8mg/day ≤ 60kg or 12mg/day ≥60kg).

Sintilimab+Lenvatinib+Radiotherapy

radiotherapy RADIATION

Radiotherapy will be completed within two weeks at a dose of 300cGy× 10 fraction

Sintilimab+Lenvatinib+Radiotherapy

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18-70, with no gender limitation;
• HCC patients who strictly met the clinical diagnostic criteria of The Code for The Diagnosis and Treatment of Primary Liver Cancer (2019 edition) or were confirmed by histopathological or cytological examination;
• BCLC stage C, no distant metastasis;
• Patients with PVTT of type VP1-2-3-4 according to Japanese VP Classification;
• The primary tumor can be resected (the remaining liver has complete vascular structure and sufficient liver volume, in line with the decision-making system of safe liver resection)
• ECOG score 0-1;
• Child-Pugh score ≤7;
• If the patient is HBV antigen positive, HBV DNA \< 500 IU/ mL, conventional antiviral treatment;
• The major organs meeting the following criteria:
• Adequate bone marrow function, defined as: Absolute neutrophil count (ANC ≥ or equal to 1.5 X 10 \^ 9 per liter (/ L)) Hemoglobin (Hb ≥ 8.5 g/dL) Platelet count ≥ 75×10 \^ 9 / L.
• Adequate liver function, defined as: Albumin \> 2.8 g/dL Bilirubin is 3.0 mg/dL or less Aspartate aminotransferase (AST), alkaline phosphatase (ALP) and alanine aminotransferase (ALT) are less than or equal to 5 ULN.
• Adequate coagulation function, defined as an international standardized ratio ( (INR) of 2.3 or less.
• Adequate renal function was defined as creatinine clearance greater than 40 mL/min (mL/min), calculated according to the Cockcroft and Gault formulas.
• Adequate pancreatic function, defined as amylase and lipase. = 1.5 x ULN.
• Adequate control of blood pressure (BP) with up to 3 antihypertensive drugs, defined as BP-lt at screening time; = 150/90 mmHg (mmHg), and there was no change in antihypertensive therapy 1 week prior to cycle 1 / day 1.

You may not qualify if:

• Extrahepatic metastasis of primary hepatocellular carcinoma;
• Diffuse liver cancer;
• Patients who had previously received targeted drugs or immune checkpoint inhibitors;
• allergic to Lenvatinib or PD-1 inhibitor ingredients;
• Patients with grade II or higher myocardial ischemia or myocardial infarction and poorly controlled arrhythmias (including QTc interval ≥470 ms); Patients with grade III \~ IV cardiac insufficiency according to NYHA standard, or left ventricular ejection fraction (LVEF) \< 50% as indicated by color doppler echocardiography;
• abnormal coagulation function (INR \> 1.5 or prothrombin time (PT) \> ULN+4 seconds or APTT \&gt; 1.5ULN), with bleeding tendency or receiving thrombolytic or anticoagulant therapy;
• pregnant or breast-feeding women; Fertile patients unwilling or unable to take effective contraceptive measures;
• have a history of mental illness or abuse of psychotropic drugs;
• patients with co-HIV infection;
• a history of liver resection, liver transplantation, interventional therapy, and other malignant tumors;
• patients with active infection;
• contraindications to radiotherapy;
• Patients with poor compliance such as floating population;
• participants in clinical trials of other experimental drugs or devices within 4 weeks;

Sponsors & Collaborators

• Beijing Tsinghua Chang Gung Hospital: lead

Study Sites (1)

Beijing Tsinghua Changgung Hospital

Beijing, Beijing Municipality, 102218, China

RECRUITING

Related Publications (1)

• Li G, Shu B, Zheng Z, Yin H, Zhang C, Xiao Y, Yang Y, Yan Z, Zhang X, Yang S, Li G, Dong J. Safety and efficacy of radiotherapy combined with lenvatinib plus PD-1 inhibitors as neo-adjuvant therapy in hepatocellular carcinoma with portal vein thrombus: protocol of an open-label, single-arm, prospective, multi-center phase I trial. Front Oncol. 2022 Nov 24;12:1051916. doi: 10.3389/fonc.2022.1051916. eCollection 2022.

  PMID: 36505833 DERIVED

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

sintilimab; lenvatinib; Radiotherapy

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Central Study Contacts

Jiahong Dong, MD

CONTACT

17346539401; ysza02008@btch.edu.cn

ShiZhong Yang

CONTACT

17346539401; ysza02008@btch.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 23, 2022
• First Posted: February 4, 2022
• Study Start: January 8, 2023
• Primary Completion: December 5, 2025
• Study Completion: December 5, 2025
• Last Updated: February 8, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)