Adjuvant Tislelizumab Plus Lenvatinib for Patients at High-risk of HCC Recurrence After Curative Resection or Ablation

NCT ID: NCT05910970

Last Updated: 2024-01-23

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-02-15
• Study Completion Date: 2025-12-31

Brief Summary

Though hepatic resection and ablation are the curative treatments for patients with hepatocellular carcinoma (HCC), the 5-years recurrence-free survival is lower than 30%. In recent years, several immune checkpoint inhibitors have been approved in advanced or unresectable HCC. No study about the safety and efficacy of adjuvant immune checkpoint inhibitors for patients with HCC after hepatectomy is reported.

Detailed Description

Hepatic resection and ablation are the best treatments for patients with early stage hepatocellular carcinoma (HCC) or selected intermediate or advanced disease. However, the postoperative 5-years recurrent rate is up to 70%, for whom recurrence is a major cause of death. In recent years, several immune checkpoint inhibitors have been approved in advanced HCC by official guidelines. At the same time, four randomizead controlled trials about adjvuant immune checkpoint inhibitors for postoperative HCC are ongoing. A prospective cohort study found adjuvant immune checkpoint inhibitors with or without tyrosine kinase inhibitors may improve recurrence-free survival of patients at high-risk of HCC recurrence after curative resection (DOI: 10.1200/JCO.2023.41.16_suppl.4119. Journal of Clinical Oncology 41, no. 16_suppl. 4119). Therefore, the investigators plan to compare the safety and efficacy of adjuvant Tislelizumab plus lenvatinib to Tislelizumab monotherapy for patients with high-risk factor of HCC recurrence after curative resection and ablation in a multicentric, prospective study.

Conditions

Hepatocellular Carcinoma; Recurrence; Immune Checkpoint Inhibitor

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Adjuvant tislelizumab plus lenvatinib

Patients at high-risk of hepatocellular carcinoma recurrence after curative resection or ablation will receive adjuvant tislelizumab plus lenvatinib treatment for six months, HCC recurrence, or unacceptable adverse events.

Group Type: EXPERIMENTAL

Adjuvant tislelizumab plus lenvatinib

Intervention Type: DRUG

Patients at high-risk of hepatocellular carcinoma recurrence after curative resection or ablation will receive adjuvant tislelizumab plus lenvatinib treatment for six months, HCC recurrence, or unacceptable adverse events.

Adjuvant tislelizumab

Patients at high-risk of hepatocellular carcinoma recurrence after curative resection or ablation will receive adjuvant tislelizumab treatment for six months, HCC recurrence, or unacceptable adverse events.

Group Type: ACTIVE_COMPARATOR

Adjuvant tislelizumab

Intervention Type: DRUG

Patients at high-risk of hepatocellular carcinoma recurrence after curative resection or ablation will receive adjuvant tislelizumab treatment for six months, HCC recurrence, or unacceptable adverse events.

Interventions

Adjuvant tislelizumab plus lenvatinib

Patients at high-risk of hepatocellular carcinoma recurrence after curative resection or ablation will receive adjuvant tislelizumab plus lenvatinib treatment for six months, HCC recurrence, or unacceptable adverse events.

Intervention Type: DRUG

Adjuvant tislelizumab

Patients at high-risk of hepatocellular carcinoma recurrence after curative resection or ablation will receive adjuvant tislelizumab treatment for six months, HCC recurrence, or unacceptable adverse events.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Age from 18 to 75 years (inclusive);
• Diagnosis of HCC confirmed by postoperative histopathology;
• Underwent curative resection, as defined based on intra- and postoperative criteria;
• With high-risk factors of recurrence after curative treatment, based on preoperative radiological imaging or pathology reports indicating a tumor at least 5 cm in diameter, micro- or macrovascular invasion (Vp1/Vp2), satellite or multinodular tumors, and/or Grade 3/4 pathology;
• No residual cancer detected by radiological imaging in the liver within 8 weeks after curative resection;
• Child-Pugh 5-7 scores liver function;
• Eastern Cooperative Oncology Group performance status of 0 or 1.

Exclusion Criteria

• Received neoadjuvant immune checkpoint inhibitors or tyrosine kinase inhibitors before resection or ablation;
• A history of other malignancies;
• History of active autoimmune or immunodeficiency diseases;
• Concurrent cardiac, pulmonary, cerebral, or renal dysfunction;
• Loss to follow-up within six months.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Guangxi Medical University

OTHER

Sponsor Role: lead

Responsible Party

Jian-Hong Zhong

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jian-Hong Zhong, Ph.D

Role: PRINCIPAL_INVESTIGATOR

Guangxi Medical University Cancer Hospital

Locations

Jian-Hong Zhong

Nanning, , China

Countries

China

Central Contacts

Jian-Hong Zhong, Ph.D

Role: CONTACT

zhongjianhong@gxmu.edu.cn

+86 771 5301253 ext. +86

Liang Ma, MD

Role: CONTACT

malianggxyd@163.com

0771 5301253 ext. +86

Facility Contacts

Jian-Hong Zhong, PhD

Role: primary

zhongjianhong66@163.com

References

Chen K, Wei W, Liu L, Deng ZJ, Li L, Liang XM, Guo PP, Qi LN, Zhang ZM, Gong WF, Huang S, Yuan WP, Ma L, Xiang BD, Li LQ, Zhong JH. Lenvatinib with or without immune checkpoint inhibitors for patients with unresectable hepatocellular carcinoma in real-world clinical practice. Cancer Immunol Immunother. 2022 May;71(5):1063-1074. doi: 10.1007/s00262-021-03060-w. Epub 2021 Sep 24.

Reference Type: BACKGROUND

PMID: 34559308 (View on PubMed)

Zhong JH, Ma L, Li LQ. Postoperative therapy options for hepatocellular carcinoma. Scand J Gastroenterol. 2014 Jun;49(6):649-61. doi: 10.3109/00365521.2014.905626. Epub 2014 Apr 10.

Reference Type: BACKGROUND

PMID: 24716523 (View on PubMed)

Hack SP, Spahn J, Chen M, Cheng AL, Kaseb A, Kudo M, Lee HC, Yopp A, Chow P, Qin S. IMbrave 050: a Phase III trial of atezolizumab plus bevacizumab in high-risk hepatocellular carcinoma after curative resection or ablation. Future Oncol. 2020 May;16(15):975-989. doi: 10.2217/fon-2020-0162. Epub 2020 Apr 30.

Reference Type: BACKGROUND

PMID: 32352320 (View on PubMed)

Bruix J, Takayama T, Mazzaferro V, Chau GY, Yang J, Kudo M, Cai J, Poon RT, Han KH, Tak WY, Lee HC, Song T, Roayaie S, Bolondi L, Lee KS, Makuuchi M, Souza F, Berre MA, Meinhardt G, Llovet JM; STORM investigators. Adjuvant sorafenib for hepatocellular carcinoma after resection or ablation (STORM): a phase 3, randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2015 Oct;16(13):1344-54. doi: 10.1016/S1470-2045(15)00198-9. Epub 2015 Sep 8.

Reference Type: BACKGROUND

PMID: 26361969 (View on PubMed)

Li L, Wu PS, Liang XM, Chen K, Zhang GL, Su QB, Huo RR, Xie RW, Huang S, Ma L, Zhong JH. Adjuvant immune checkpoint inhibitors associated with higher recurrence-free survival in postoperative hepatocellular carcinoma (PREVENT): a prospective, multicentric cohort study. J Gastroenterol. 2023 Oct;58(10):1043-1054. doi: 10.1007/s00535-023-02018-2. Epub 2023 Jul 14.

Reference Type: BACKGROUND

PMID: 37452107 (View on PubMed)

Other Identifiers

PREVENT-2

Identifier Type: -

Identifier Source: org_study_id