Trial Title:
Lenvatinib Combined With Tislelizumab and TACE Applied as Neoadjuvant Regimen for the Patients of CNLC Stage IB and IIA Hepatocellular Carcinoma With High-risk Recurrence Factors
NCT ID:
NCT05920863
Condition:
Hepatocellular Carcinoma
Lenvatinib
Tislelizumab
TACE
Pharmorubicin
Oxaliplatin
Conditions: Official terms:
Carcinoma
Carcinoma, Hepatocellular
Recurrence
Lenvatinib
Tislelizumab
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
This is a prospective, single-arm, open phase II clinical study
Primary purpose:
Treatment
Masking:
None (Open Label)
Masking description:
Prior to enrollment in the study, doctors asked and recorded the patient's medical
history, and if eligible participants volunteered to participate in the study, they would
sign informed consent.If they are not willing to participate in the study, we will do the
usual treatment
Intervention:
Intervention type:
Procedure
Intervention name:
TACE
Description:
TACE: pharmorubicin 30mg, oxaliplatin 50mg, cycle 4-5 week.
Arm group label:
Experimental
Intervention type:
Drug
Intervention name:
Tislelizumab, Lenvatinib
Description:
Tislelizumab: 200mg, cycle 3 week. Lenvatinib: weight <60kg, 8mg/day; weight ≥60kg,
12mg/day.
Arm group label:
Experimental
Summary:
This is a monocenter, single-arm, open-label study to evaluate the efficacy and safety of
Lenvatinib combined with Tislelizumab and TACE applied as neoadjuvant regimen for the
patients of CNLC stage IB and IIA hepatocellular carcinoma with high risk of recurrence
Primary outcome: Major pathological response (MPR) Secondary outcomes: pathological
complete response (pCR), R0 resection rate, objective response rate (ORR), disease
control rate (DCR), treatment-related adverse events (TRAE)
Detailed description:
Surgical treatment is dominant in the treatment of liver cancer, however, its
postoperative recurrence rate is high, and the recurrence and metastasis rate in 5 years
is as high as 70%. In particular, surgical resection for some large hepatocellular
carcinoma adjacent to large vessels or located in middle areas always induces narrow and
even no surgical margin, which may increase the risk of postoperative recurrence and
decrease the overall survival rate. Preoperative neoadjuvant therapy for resectable
hepatocellular carcinoma with high risk of recurrence is still controversial nationally
and internationally, none consensus have been reached about neoadjuvant therapy.
As a classical treatment for liver cancer, TACE can induce tumor ischemia and necrosis
through the infusion of chemotherapy drugs and embolic materials into target areas.
However, TACE as neoadjuvant therapy alone has no improvement in tumor recurrence-free
survival time and overall survival rate. Lenvatinib is a multi-target tyrosine kinase
inhibitor and inhibits neovascularization and lymphangiogenesis by targeting VEGF1-3 and
FGFR. moreover, lenvatinib also has immunomodulatory effects. A number of studies have
shown that a variety of combination therapies have been carried out on the basis of
Lenvatinib, and exciting outcome has been achieved by combined therapy regimens,
including local therapy combined with systemic therapy and multi-drugs systemic therapy.
Neoadjuvant therapy will performe on CNLC stage IB and Stage IIA HCC patients with high
risk of recurrence (patients with narrow or no surgical margin and preoperative tumor
marker AFP+PIVKA≥1600). MPR, pCR,1-year recurrence-free survival (RFS), and
treatment-related adverse reactions (TRAE) were evaluated.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Aged 18-75 years old (inclusive);
2. HCC is confirmed by preoperative pathological examination or meet the criterion of
diagnosis and treatment norms of primary HCC issued by health commission, PRC. No
prior systemic chemotherapy, immunotherapy, targeted therapy, or other anti-tumor
treatments for HCC;
3. Patients with CNLC IB or IIA stage tumors before surgery and meeting the following
conditions: radiological evaluation shows narrow or none surgical margins, and
preoperative tumor markers AFP+PIVKA is greater than 1600.
4. ECOG score of 0 before the first administration of the study drug;
5. Child-Pugh scores is 5-6 points and liver function is grade A;
6. Expected survival time of at least 16 weeks;
7. Pre-administration organ function levels meet the requirements and are tolerant of
surgery. The functional indicators of important organs meet the following
requirements: hemoglobin ≥90g/L, neutrophil count ≥1.5×10⁹/L, platelet count
≥100×10⁹/L; aspartate aminotransferase or alanine aminotransferase ≤5 times the
upper limit of normal (ULN), alkaline phosphatase ≤2.5 ULN, serum albumin ≥30g/L;
serum creatinine <1.5 ULN; international normalized ratio (INR) ≤2 or prothrombin
time (PT) within the upper limit of normal range ≤6 seconds; serum creatinine ≤1.5
ULN, creatinine clearance rate ≥60 mL/min.
8. Male and female participants of childbearing potential must agree to use effective
contraception throughout the study period;
9. Sign an informed consent form and agree to provide previously stored tumor tissue
specimens or fresh biopsy specimens of the tumor lesion.
Exclusion Criteria:
1. Pathologically diagnosed as non-hepatocellular carcinoma;
2. Previously received anti-tumor treatments such as chemotherapy, radiotherapy,
radiofrequency ablation, intervention, targeted therapy, immunotherapy or surgical
treatment for liver cancer (excluding previous non-tumor-related surgery or
diagnostic biopsy);
3. CNLC stage is IA, IIB or worse.
4. Viral load limited to hepatitis B virus (HBV) DNA>2000 copies/ml, hepatitis C virus
(HCV) RNA>1000;
5. Long-term steroid users who require long-term systemic steroid therapy (equivalent
to >10 mg of prednisone per day) or any other form of immunosuppressive treatment;
6. Significant clinical bleeding or bleeding tendency within 3 months before enrollment
or currently undergoing thrombolysis or anticoagulation treatment;
7. Complete intestinal obstruction and incomplete intestinal obstruction requiring
treatment, but patients who have had obstruction relieved by fistula or stent
placement can be enrolled;
8. Active severe clinical infection (> grade 2, NCI-CTCAE version 5.0), including
active tuberculosis; history of active tuberculosis infection for more than 1 year
before enrollment, not treated with regular anti-tuberculosis treatment or
tuberculosis still in the active period; active known or suspected autoimmune
disease;
9. Uncontrolled diabetes (fasting blood glucose ≥10 mmol/L), severe lung disease (such
as acute pulmonary disease, pulmonary fibrosis that affects lung function,
interstitial lung disease. Excluding recovered radiation pneumonitis);
10. Clinically significant cardiovascular disease; hypertension which cannot be well
controlled by anti-hypertensive drugs (systolic blood pressure ≥140 mmHg or
diastolic blood pressure ≥90 mmHg);
11. Patients undergoing renal replacement therapy;
12. History of other malignant tumors within the past 5 years. Excluding cured basal
cell carcinoma or cervical intraepithelial neoplasia;
13. Other patients who are expected to be unable to tolerate surgical treatment;
14. Patients who have had allergic reactions to any component of the study drug;
15. Presence of alcohol dependence, mental illness, pregnancy (or lactation) or other
conditions that are not suitable for clinical trials.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
1# Banshan East Rd. Zhejiang cancer hospital
Address:
City:
Hangzhou
Zip:
310022
Country:
China
Status:
Recruiting
Contact:
Last name:
Yuhua Zhang, M.D.
Phone:
+86-0571-88128058
Email:
drzhangyuhua@126.com
Contact backup:
Last name:
Jia Wu
Phone:
+86-0571-88128052
Email:
tkds123@qq.com
Start date:
July 1, 2023
Completion date:
March 2026
Lead sponsor:
Agency:
Zhejiang Cancer Hospital
Agency class:
Other
Source:
Zhejiang Cancer Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05920863
