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

Hepatocellular Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05225116
• Other study ID #: 21323-0-03
• Status: Recruiting
• Phase: Phase 1
• Start date: January 8, 2023
• Est. completion date: December 5, 2025

Study information

• Verified date: January 2023
• Source: Beijing Tsinghua Chang Gung Hospital
• Contact: Jiahong Dong, MD
• Phone: 17346539401
• Email: ysza02008[@]btch.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: December 5, 2025
• Est. primary completion date: December 5, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma

Intervention

Drug:
• Sintilimab
Sintilimab will be at a dose of 200mg,Q3W
• 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

Locations

Country	Name	City	State
China	Beijing Tsinghua Changgung Hospital	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Beijing Tsinghua Chang Gung Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety(CTCAE v5.0)	Number of patients who reported incidence of grade =3 treatment related adverse events.	up to 5 years
Primary	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	Major Pathological Response(MPR)	Survival tumor =10% during surgery	Within 3 months after surgery
Secondary	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
Secondary	Imaging-pathology Concordance Rate	Imaging-pathology Concordance Rate	Within 3 months after surgery
Secondary	PVTT regression rate	The fading rate of PVTT	Within 3 months after surgery
Secondary	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
Secondary	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