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

Safety and Efficacy of Lenvatinib and Anti-PD1 Antibody Combined With Radiotherapy Neoadjuvant Treatment for Resectable Hepatocellular Carcinoma With PVTT,Prospective, Multicenter, Single-arm Study

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.

Study Overview

• Status: Recruiting
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Drug: Sintilimab; Drug: Lenvatinib; Radiation: radiotherapy

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 102218
      • Recruiting
      • Beijing Tsinghua Changgung Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Aged 18-70, with no gender limitation;
2. 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;
3. BCLC stage C, no distant metastasis;
4. Patients with PVTT of type VP1-2-3-4 according to Japanese VP Classification;
5. 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)
6. ECOG score 0-1;
7. Child-Pugh score ≤7;
8. If the patient is HBV antigen positive, HBV DNA < 500 IU/ mL, conventional antiviral treatment;

9. The major organs meeting the following criteria:

   1. 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.
   2. 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.
   3. Adequate coagulation function, defined as an international standardized ratio ( (INR) of 2.3 or less.
   4. Adequate renal function was defined as creatinine clearance greater than 40 mL/min (mL/min), calculated according to the Cockcroft and Gault formulas.
   5. Adequate pancreatic function, defined as amylase and lipase. = 1.5 x ULN.
10. 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.
11. Patients are expected to survive longer than 3 months.
12. No pregnancy or pregnancy plan.
13. Subjects voluntarily joined the study and signed informed consent with good compliance and follow-up.

Exclusion Criteria:

1. Extrahepatic metastasis of primary hepatocellular carcinoma;
2. Diffuse liver cancer;
3. Patients who had previously received targeted drugs or immune checkpoint inhibitors;
4. allergic to Lenvatinib or PD-1 inhibitor ingredients;
5. 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;
6. abnormal coagulation function (INR > 1.5 or prothrombin time (PT) > ULN+4 seconds or APTT > 1.5ULN), with bleeding tendency or receiving thrombolytic or anticoagulant therapy;
7. pregnant or breast-feeding women; Fertile patients unwilling or unable to take effective contraceptive measures;
8. have a history of mental illness or abuse of psychotropic drugs;
9. patients with co-HIV infection;
10. a history of liver resection, liver transplantation, interventional therapy, and other malignant tumors;
11. patients with active infection;
12. contraindications to radiotherapy;
13. Patients with poor compliance such as floating population;
14. participants in clinical trials of other experimental drugs or devices within 4 weeks;
15. those considered unsuitable for inclusion by the researcher.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Sintilimab+Lenvatinib+Radiotherapy	Drug: Sintilimab; Sintilimab will be at a dose of 200mg,Q3W; Drug: Lenvatinib; On the first day of the trial, Lenvatinib will be taken orally once daily （8mg/day ≤ 60kg or 12mg/day ≥60kg).; Radiation: radiotherapy; Radiotherapy will be completed within two weeks at a dose of 300cGy× 10 fraction

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major Pathological Response(MPR)	Survival tumor ≤10% during surgery	Within 3 months after surgery
Objective Response Rate(ORR)	Efficacy included objective response (includes complete and partial response) according to modified RECIST 1.1 for HCC	within 1 week before surgery
Imaging-pathology Concordance Rate	Imaging-pathology Concordance Rate	Within 3 months after surgery
PVTT regression rate	The fading rate of PVTT	Within 3 months after surgery
Median Overall survival(mOS)	mOS is defined as the median difference (in months) between the date of study enrollment to the date death due to any cause	up to 5 years
Recurrence free survival(RFS)	From radical resection to the date of the first documented tumor into recurrence or death from any cause, whichever occurred first	1 year after surgery

Collaborators and Investigators

• Sponsor: Beijing Tsinghua Chang Gung Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 8, 2023
• Primary Completion (ANTICIPATED): December 5, 2025
• Study Completion (ANTICIPATED): December 5, 2025

Study Registration Dates

• First Submitted: January 23, 2022
• First Submitted That Met QC Criteria: January 26, 2022
• First Posted (ACTUAL): February 4, 2022

Study Record Updates

• Last Update Posted (ACTUAL): February 8, 2023
• Last Update Submitted That Met QC Criteria: February 6, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Lenvatinib
• Other Study ID Numbers: 21323-0-03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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