Hepatocellular CarcinomaPhase 2NCT05920863
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
A Phase 2 study testing TACE and Tislelizumab, Lenvatinib in people with Hepatocellular Carcinoma and Lenvatinib, run by Zhejiang Cancer Hospital at 1 site in China.
Trial 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)… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Hepatocellular Carcinoma, Lenvatinib, Tislelizumab
- What is being tested?
- TACE and Tislelizumab, Lenvatinib
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 1 siteChina
- Study dates
- 1 Jul 2023to 31 Dec 2025
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Aged 18-75 years old (inclusive);
- 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;
- 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.
- ECOG score of 0 before the first administration of the study drug;
- Child-Pugh scores is 5-6 points and liver function is grade A;
- Expected survival time of at least 16 weeks;
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- 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.
- Male and female participants of childbearing potential must agree to use effective contraception throughout the study period;
- Sign an informed consent form and agree to provide previously stored tumor tissue specimens or fresh biopsy specimens of the tumor lesion.
Who cannot join
- Pathologically diagnosed as non-hepatocellular carcinoma;
- 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);
- CNLC stage is IA, IIB or worse.
- Viral load limited to hepatitis B virus (HBV) DNA>2000 copies/ml, hepatitis C virus (HCV) RNA>1000;
- 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;
- Significant clinical bleeding or bleeding tendency within 3 months before enrollment or currently undergoing thrombolysis or anticoagulation treatment;
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- Complete intestinal obstruction and incomplete intestinal obstruction requiring treatment, but patients who have had obstruction relieved by fistula or stent placement can be enrolled;
- 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;
- 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);
- 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);
- Patients undergoing renal replacement therapy;
- History of other malignant tumors within the past 5 years. Excluding cured basal cell carcinoma or cervical intraepithelial neoplasia;
- Other patients who are expected to be unable to tolerate surgical treatment;
- Patients who have had allergic reactions to any component of the study drug;
- Presence of alcohol dependence, mental illness, pregnancy (or lactation) or other conditions that are not suitable for clinical trials.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
1# Banshan East Rd. Zhejiang cancer hospital
Hangzhou, Zhejiang, 310022
Yuhua - Zhang, M.D., +86-0571-88128058, drzhangyuhua@126.com
Jia - Wu, +86-0571-88128052, tkds123@qq.com
About this study
Official 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 of Recurrence: Study Protocol of a Monocenter, Single-arm, Open Label Clincal Trail
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)
Read the 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.
- Conditions
- Hepatocellular Carcinoma, Lenvatinib, Tislelizumab, TACE, Pharmorubicin, Oxaliplatin
- Being tested
- TACE, Tislelizumab, Lenvatinib
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TACEProcedure or surgery
TACE: pharmorubicin 30mg, oxaliplatin 50mg, cycle 4-5 week.
Tislelizumab, LenvatinibDrug
Tislelizumab: 200mg, cycle 3 week. Lenvatinib: weight <60kg, 8mg/day; weight ≥60kg, 12mg/day.
| Study group | Role | What they receive |
|---|---|---|
| Experimental | Experimental | 1. TACE: pharmorubicin 30mg, oxaliplatin 50mg, cycle 4-5 week.
2. Tislelizumab: 200mg, cycle 3 week.
3. Lenvatinib: weight <60kg, 8mg/day; weight ≥60kg, 12mg/day. Receives: Procedure: TACE; Drug: Tislelizumab, Lenvatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Major pathological response
Proportion of residual tumor ingredient lesser than 30% in the postoperative pathological result.
Measured: Up to 16 weeks
Secondary outcomes (6)
Pathological complete response
None residual tumor ingredient detected in the postoperative pathological result.
Measured: Up to 16 weeks
R0 resection rate
The proportion of patients achieved a complete resection with negative margin.
Measured: Up to 16 weeks
Objective response rate (ORR)
he proportion of participants with a documented, confirmed complete response or partial response per RECIST v1.1
Measured: Up to 4 cycle treatment (each cycle is 4 weeks), an average of 16 weeks.
disease control rate (DCR)
The percentage of patients who have achieved either a complete response (CR), a partial response (PR), or stable disease (SD) after undergoing treatment for their cancer.
Measured: Up to 4 cycle treatment (each cycle is 4 weeks), an average of 16 weeks.
treatment-related adverse events (TRAE)
Adverse event that occurs during or after treatment
Measured: Up to 4 cycle treatment (each cycle is 4 weeks), an average of 16 weeks.
Recurrence-free survival (RFS)
The length of time after cancer treatment during which a patient remains free from any signs or symptoms of cancer recurrence.
Measured: Up to 4 cycle treatment (each cycle is 4 weeks), an average of 16 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jun 2023
- Study start1 Jul 2023
- Primary completion31 Dec 2025 (estimated)
- Study completion31 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- More trials run by Zhejiang Cancer HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- This is a prospective, single-arm, open phase II clinical study
- Masking
- None (open label)
- Enrolment
- 35 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Zhejiang Cancer Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Yuhua Zhang, MD, Zhejiang Cancer Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05920863
- Sponsor's protocol ID
- 20230408
- Status last verified
- Dec 2024
- First submitted
- 17 Jun 2023
- Last updated
- 11 Feb 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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 of Recurrence: Study Protocol of a Monocenter, Single-arm, Open Label Clincal Trail
- ClinicalTrials.gov ID
- NCT05920863
- Acronym / sponsor ID
- 20230408
- Conditions
- Hepatocellular Carcinoma, Lenvatinib, Tislelizumab, TACE, Pharmorubicin, Oxaliplatin
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 35 participants (estimated)
- Lead sponsor
- Zhejiang Cancer HospitalUniversity, hospital or other
- Study start
- 1 Jul 2023 (actual)
- Primary completion
- 31 Dec 2025 (estimated)
- Study completion
- 31 Dec 2025 (estimated)
- First posted
- 27 Jun 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This is a prospective, single-arm, open phase II clinical study
| Arm | Type | Receives |
|---|---|---|
| Experimental | Experimental | Procedure: TACE, Drug: Tislelizumab, Lenvatinib1. TACE: pharmorubicin 30mg, oxaliplatin 50mg, cycle 4-5 week. 2. Tislelizumab: 200mg, cycle 3 week. 3. Lenvatinib: weight <60kg, 8mg/day; weight ≥60kg, 12mg/day. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Aged 18-75 years old (inclusive);
- 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;
- 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.
- ECOG score of 0 before the first administration of the study drug;
- Child-Pugh scores is 5-6 points and liver function is grade A;
Key exclusion criteria (15 listed)
- Pathologically diagnosed as non-hepatocellular carcinoma;
- 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);
- CNLC stage is IA, IIB or worse.
- Viral load limited to hepatitis B virus (HBV) DNA>2000 copies/ml, hepatitis C virus (HCV) RNA>1000;
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TACETACE: pharmorubicin 30mg, oxaliplatin 50mg, cycle 4-5 week. | Procedure or surgery | Experimental |
| Tislelizumab, LenvatinibTislelizumab: 200mg, cycle 3 week. Lenvatinib: weight <60kg, 8mg/day; weight ≥60kg, 12mg/day. | Drug | Experimental |
Primary outcome
Major pathological response
Time frame: Up to 16 weeks
Proportion of residual tumor ingredient lesser than 30% in the postoperative pathological result.
6 secondary outcomes
Pathological complete response
Time frame: Up to 16 weeks
R0 resection rate
Time frame: Up to 16 weeks
Objective response rate (ORR)
Time frame: Up to 4 cycle treatment (each cycle is 4 weeks), an average of 16 weeks.
disease control rate (DCR)
Time frame: Up to 4 cycle treatment (each cycle is 4 weeks), an average of 16 weeks.
treatment-related adverse events (TRAE)
Time frame: Up to 4 cycle treatment (each cycle is 4 weeks), an average of 16 weeks.
Recurrence-free survival (RFS)
Time frame: Up to 4 cycle treatment (each cycle is 4 weeks), an average of 16 weeks.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Feb 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing TACE and Tislelizumab, Lenvatinib in people with Hepatocellular Carcinoma and Lenvatinib, run by Zhejiang Cancer Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 11 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Yuhua Zhang, MD (+86-0571-88128058, drzhangyuhua@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Major pathological response (time frame: Up to 16 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Feb 2025.