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Trial Title:
Neoadjuvant SBRT Combined With Lenvatinib and Pucotenlimab for Resectable Hepatocellular Carcinoma
NCT ID:
NCT06524466
Condition:
Resectable Hepatocellular Carcinoma
Macrovascular Invasion
CNLC IIIA Stage
Conditions: Official terms:
Carcinoma
Carcinoma, Hepatocellular
Lenvatinib
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Active, not recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Neoadjuvant SBRT combined with Lenvatinib and Pucotenlimab
Description:
SBRT: SBRT will be performed within 2-4 weeks after enrollment. The total radiation dose
will be 24 Gy, delivered in 3 fractions on alternate days, to be completed within one
week.
Lenvatinib: 8mg/day, begin immediately after enrollment. Lenvatinib should be
discontinued one week before surgery.
Pucotenlimab: 200mg，3-week interval between cycles, begin immediately after enrollment, a
total of four cycles of Puco treatment must be completed before surgery.
Surgical resection will be performed within 10-16 weeks after the completion of SBRT.
Arm group label:
Experimental arm
Summary:
At the time of diagnosis, the majority of hepatocellular carcinoma (HCC) patients are at
the intermediate to advanced stages, with a 50-70% incidence of macrovascular invasion
(including portal vein, hepatic vein, inferior vena cava, or bile duct invasion).
Tyrosine kinase inhibitors (TKI, including lenvatinib and sorafenib) or a combination of
TKIs and immune therapy is one of the standard treatment options recommended by HCC
guidelines. However, numerous retrospective studies have reported that for surgically
resectable HCC with macrovascular invasion, surgical resection yields better efficacy
than non-surgical treatments (including transarterial interventional therapies and/or
systemic therapies). Nevertheless, the postoperative recurrence rate remains exceedingly
high, exceeding 80%. Therefore, determining comprehensive approaches to enhance surgical
radicality and reduce postoperative recurrence rates is a current research hotspot.
Recent studies have found that neoadjuvant therapy (including immunotherapy alone or in
combination with TKI) before surgery can reduce postoperative recurrence rates and extend
survival rates. Moreover, SBRT combined with TKI and immunotherapy has a sensitizing
effect, particularly showing good sensitivity and control rates for vascular invasion.
Thus, this study aims to conduct a prospective, single-arm phase II clinical trial
targeting patients with surgically resectable HCC with macrovascular invasion. The
primary endpoints are objective response rate (ORR) and treatment completion rate, to
evaluate the efficacy and safety of the preoperative neoadjuvant therapy with the
combination of SBRT, lenvatinib, and pucotenlimab (an anti PD-1 drug). The secondary
endpoints include progression-free survival (PFS), overall survival (OS), incidence of
adverse events, pathological response rate, and incidence of surgical complications, to
preliminarily evaluate the efficacy of the neoadjuvant therapy with this triple regimen.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. All patients must be pathologically confirmed to have hepatocellular carcinoma by
biopsy；
2. No previous antitumor treatment;
3. Tumor number ≤ 3, diameter ≤ 10 cm, confined to one lobe of the liver or the middle
lobe, evaluated by a surgeon as resectable;
4. Combined with vascular invasion, with the following extents: unilateral portal vein
invasion without extending beyond the main portal vein; hepatic vein invasion not
reaching the inferior vena cava; unilateral bile duct invasion not reaching the
common hepatic duct;
5. No extra-hepatic metastasis or lymph node metastasis.
6. Normal liver volume ≥ 700 cc;
7. Patient KPS ≥ 90;
8. Liver function Child-Pugh class A;
9. Estimated survival of more than 6 months;
10. Function of important organs meets the following requirements: white blood cells ≥
4.0×10^9/l, neutrophils ≥ 1.5×10^9/l, platelets ≥ 80.0×10^9/l, hemoglobin ≥ 90 g/l;
serum albumin ≥ 2.8 g/dl; total bilirubin ≤ 1.5× ULN, ALT/AST/ALP ≤ 2.5 × ULN; serum
creatinine ≤ 1.5 × ULN or creatinine clearance rate > 60 mL/min; no severe organic
diseases;
11. The subject must be able to understand and voluntarily sign a written informed
consent form, and must sign the informed consent form prior to any specific
procedure of the study, agreeing to comply with the medication and postoperative
follow-up requirements as designed in this study.
Exclusion Criteria:
1. Combined with severe impairment of functions of other important organs such as
heart, lungs, and kidneys; active infections other than viral hepatitis or other
serious comorbid conditions, making the patient unable to tolerate treatment;
2. Diffuse type of HCC, or tumor volume exceeding 50% of liver volume;
3. Portal vein invasion extending beyond the main tract of the portal vein, or hepatic
vein invasion reaching the inferior vena cava, or bile duct invasion extending
beyond the common hepatic duct;
4. Contraindications to surgical resection, SBRT and immunotherapy;
5. History of other malignant tumors;
6. Combined with immunological diseases or other conditions requiring long-term steroid
treatment;
7. Known or suspected allergy to the study drug or any drugs administered in connection
with this trial;
8. History of organ transplantation;
9. Pregnant or breastfeeding women;
10. Other factors that may affect patient enrollment and assessment outcomes;
11. Refusal to follow-up according to the requirements set by the study protocol, and
refusal to sign the informed consent form.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Sun Yat-sen University Cancer Center
Address:
City:
Guangzhou
Zip:
510060
Country:
China
Start date:
July 23, 2024
Completion date:
December 1, 2026
Lead sponsor:
Agency:
Sun Yat-sen University
Agency class:
Other
Source:
Sun Yat-sen University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06524466
