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

NCT ID: NCT05225116

Last Updated: 2023-02-08

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-01-08
• Study Completion Date: 2025-12-05

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Sintilimab+Lenvatinib+Radiotherapy

Group Type: EXPERIMENTAL

Sintilimab

Intervention Type: DRUG

Sintilimab will be at a dose of 200mg,Q3W

Lenvatinib

Intervention Type: DRUG

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

radiotherapy

Intervention Type: RADIATION

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

Interventions

Sintilimab

Sintilimab will be at a dose of 200mg,Q3W

Intervention Type: DRUG

Lenvatinib

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

Intervention Type: DRUG

radiotherapy

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

Intervention Type: RADIATION

Eligibility Criteria

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 &gt; 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Beijing Tsinghua Chang Gung Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Beijing Tsinghua Changgung Hospital

Beijing, Beijing Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Jiahong Dong, MD

Role: CONTACT

ysza02008@btch.edu.cn

17346539401

ShiZhong Yang

Role: CONTACT

ysza02008@btch.edu.cn

17346539401

Facility Contacts

ShiZhong Yang

Role: primary

ysza02008@btch.edu.cn

17346539401

Guangxin Li

Role: backup

lgxa02385@btch.edu.cn

15810890312

References

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.

Reference Type: DERIVED

PMID: 36505833 (View on PubMed)

Other Identifiers

21323-0-03

Identifier Type: -

Identifier Source: org_study_id