This is a parallel assigned, open-label, perspective trial studying the safety and efficacy of intensity-modulated radiotherapy (IMRT) combined with PD-1 Blockade and Lenvatinib for Hepatocellular Carcinoma (HCC) with Vp3 Portal Vein Tumor Thrombus (PVTT, Japanese Liver Cancer Study Group classification) before liver transplantation.
In most criteria (e.g.Milan, UCSF, Up-to-seven), PVTT remains as an absolute contraindication for liver transplant due to the high rate of recurrence and poor prognosis. Neoadjuvant therapy has induced pathological responses in multiple tumor types and might decrease the risk of postoperative recurrence in HCC. The primary endpoint is the necrosis rate of PVTT and the primary tumor. Participants receive PD-1 Blockade (Pembrolizumab,Sintilimab, Camrelizumab,Tislelizumab) 200 mg intravenously on day 1 of a regular treatment cycle and Lenvatinib Mesylate Capsule (Lenvima®) 8 mg orally once daily. Neoadjuvant IMRT will be initiated at the third treatment cycle, and the dose prescription of IMRT is for planning target volume (PTV). The prescription dose to 95%PTV should be ≥50 Gy and ≤60 Gy, and been given in daily dose fractions of 2 Gy, 5 days per week. And the final prescription dose is determined according to dose constraints for organs at risk.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
78
Neoadjuvant IMRT will be initiated at the third treatment cycle, and the dose prescription of IMRT is for planning target volume (PTV). The prescription dose to 95%PTV should be ≥50 Gy and ≤60 Gy, and been given in daily dose fractions of 2 Gy, 5 days per week. And the final prescription dose is determined according to dose constraints for organs at risk.
Participants receive PD-1 Blockade (Pembrolizumab 200mg,Sintilimab 200mg, Camrelizumab 200mg,Tislelizumab 200mg) 100-200 mg intravenously on day 1 of a regular treatment cycle until \>42 days before liver transplantation or unacceptable toxicity develops. Participants receive Lenvatinib Mesylate Capsule (Lenvima®) 8 mg orally once daily until \>7 days before liver transplantation.
Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University
Shanghai, China
PVTT RR/NR
Portal vein tumor thrombus related Response and Necrosis Rate
Time frame: up to 12 months
Alpha Fetoprotein Response (AFP-R)
AFP-R is defined as a \>20% decrease in AFP serum level from baseline to the time of liver transplant, if liver transplant is not possible, the final AFP level would be measured as the AFP level at 12 months.
Time frame: up to 12 months
Progression-free survival (PFS)
PFS is defined as the time from the date of treatment initiation to the date of the first observation of progressive disease (PD) by independent radiologic review according to mRECIST criteria or death from any cause.
Time frame: up to 12 months
Objective Response Rate (ORR)
RR is defined as the proportion of patients whose tumor volume has reached a predetermined value and can maintain a minimum time limit, including complete response(CR) and partial response(PR) by independent radiologic review according to mRECIST criteria.
Time frame: up to 12 months
Time to Progression (TTP)
TTP is defined as the duration from the date of patient recruited to the first progress at any site or the date of death from any cause.
Time frame: up to 12 months
Duration of response (DOR)
DOR is defined as the duration from the date that measurement criteria are met for CR or PR to the first progress at any site or the date of death from any cause.
Time frame: up to 12 months
Qiang Xia, MD, Ph.D
CONTACT
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Sintilimab is a recombinant anti-human PD-1 monoclonal antibody.
Camrelizumab is a humanized anti-human PD-1 monoclonal antibody.
Tislelizumab is a recombinant anti-human PD-1 monoclonal antibody.
Lenvatinib (Lenvima®, Eisai China) is a novel angiogenesis inhibitor which targets vascular endothelial growth factor 1-3, fibroblast growth factor receptor 1-4, platelet-derived growth factor receptor β, RET and KIT.