Clinical trial NCT05225116: Safety and Efficacy of Lenvatinib and Anti-PD1 Antibody Combined With Radiotherapy Neoadjuvant Treatment for Resectable Hepatocellular Carcinoma With PVTT
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Hepatocellular Carcinoma
Lead sponsor: Beijing Tsinghua Chang Gung Hospital
Sponsor class: OTHER
First posted: 2022-02-04
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Safety(CTCAE v5.0)
timeFrame: up to 5 years
measure: Number of patients who complete pre-op treatment and proceed to surgery
timeFrame: up to 5 years
Secondary outcomes:
measure: Major Pathological Response(MPR)
timeFrame: Within 3 months after surgery
measure: Objective Response Rate(ORR)
timeFrame: within 1 week before surgery
measure: Imaging-pathology Concordance Rate
timeFrame: Within 3 months after surgery
measure: PVTT regression rate
timeFrame: Within 3 months after surgery
measure: Median Overall survival(mOS)
timeFrame: up to 5 years
measure: Recurrence free survival(RFS)
timeFrame: 1 year after surgery
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Tsinghua Changgung Hospital
state: Beijing
Study officials:
References: