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The purpose of this study is to evaluate the safety and efficacy of transarterial chemoembolization (TACE) in combination with PD-1/PD-L1 Inhibitors and molecular target therapies in patients with Intermediate-stage hepatocellular carcinoma (HCC).
Transarterial chemoembolization (TACE) can induce immunogenic cell death and tumor-specific immune response which results in the release of tumor antigens and transform "cold" tumors with lacking immune effector cells into "hot" tumors with immune effector cells infiltration. This provides a theoretical basis for TACE combined with immune checkpoint inhibitors (ICIs) in hepatocellular carcinoma (HCC) patients. The purpose of this study is to evaluate the safety and efficacy of transarterial chemoembolization (TACE) in combination with PD-1/PD-L1 Inhibitors and molecular target therapies(including, VEGF-TKI/ bevacizumab) in patients with Intermediate-stage HCC. This real-world study also would like to explore the optimal combined treatment and subgroup of HCC patients for providing further information for clinical practice and trials.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Study group: TACE+PD-1/PD-L1 inhibitors+VEGF-TKI/bevacizumab | TACE was performed up to 3 months after the first PD-1/PD-L1 inhibitor/anti-angiogenic drug treatment or within 1 month before treatment. The interval between first use PD-1/PD-L1 inhibitors and anti-angiogenesis drugs ≤1 week; |
| |
| Control group: TACE | TACE monotherapy |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| PD-1/PD-L1 inhibitors+VEGF-TKI/bevacizumab | Drug | PD-1/PD-L1 inhibitors: atezolizumab, sintilimab, pembrolizumab, nivolumab, camrelizumab, tislelizumab, toripalimab, durvalumab, penpulimab, and other ICIs; VEGF-TKI/bevacizumab: sorafenib, lenvatinib, donafenib, apatinib, anlotinib, bevacizumab/ bevacizumab biosimilar, and other anti-angiogenesis drugs; Both PD-1/PD-L1 inhibitors and anti-angiogenesis drugs only include marketed drugs but are not limited to HCC approval. |
| Measure | Description | Time Frame |
|---|---|---|
| Progression free survival(PFS) per Modified Response Evaluation Criteria in Solid Tumors (mRECIST) | The PFS is defined as the time from the initiation of any combination treatment to the first documented progressive disease (according to mRECIST) or death due to any cause, whichever occurs first. | up to approximately 2 years |
| Overall Survival(OS) | The OS is defined as the time from the initiation of any combination treatment to death due to any cause. | up to approximately 2 years |
| Measure | Description | Time Frame |
|---|---|---|
| PFS per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) | The PFS is defined as the time from the initiation of any combination treatment to the first documented progressive disease (according to RECIST 1.1) or death due to any cause, whichever occurs first. | up to approximately 2 years |
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Inclusion Criteria:
Exclusion Criteria:
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Patients with intermediate HCC who received TACE in combination with PD-1/PD-L1 inhibitors and molecular target therapies under real-world practice conditions.
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| Name | Affiliation | Role |
|---|---|---|
| Gao-Jun Teng, M.D. | Zhongda hospital, Southeast university, Nanjing, China | Principal Investigator |
| Zheng-Gang Ren, M.D. | Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Gao-Jun Teng | Nanjing | China | ||||
| Zheng-Gang Ren |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32430997 | Background | Llovet JM, Villanueva A, Marrero JA, Schwartz M, Meyer T, Galle PR, Lencioni R, Greten TF, Kudo M, Mandrekar SJ, Zhu AX, Finn RS, Roberts LR; AASLD Panel of Experts on Trial Design in HCC. Trial Design and Endpoints in Hepatocellular Carcinoma: AASLD Consensus Conference. Hepatology. 2021 Jan;73 Suppl 1:158-191. doi: 10.1002/hep.31327. Epub 2020 Sep 9. No abstract available. | |
| 33479224 |
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| ID | Term |
|---|---|
| D006528 | Carcinoma, Hepatocellular |
| ID | Term |
|---|---|
| D000230 | Adenocarcinoma |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
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|
| TACE | Procedure | TACE: cTACE (conventional TACE) or dTACE (drug-eluting beads TACE); |
|
| Objective response rate(ORR) per mRECIST |
The ORR is defined as the proportion of patients with a documented complete response(CR) or partial response(PR) per mRECIST. |
| up to approximately 2 years |
| Duration of Response (DOR) per mRECIST | DOR is determined by disease assessment and is defined as the time from the first documented evidence of a response of CR or PR until the first documented disease progression (according to mRECIST) or death due to any cause, whichever occurs first. | up to approximately 2 years |
| Disease Control Rate (DCR) per mRECIST | DCR is defined as the percentage of participants who have a best overall response of CR, PR, or stable disease (SD) per mRECIST. | up to approximately 2 years |
| ORR per RESCIST 1.1 | The ORR is defined as the proportion of patients with a documented complete response(CR) or partial response(PR) per RECIST 1.1. | up to approximately 2 years |
| DOR per RESCIST 1.1 | DOR is determined by disease assessment and is defined as the time from the first documented evidence of a response of CR or PR until the first documented disease progression (according to RESCIST 1.1) or death due to any cause, whichever occurs first. | up to approximately 2 years |
| DCR per RESCIST 1.1 | DCR is defined as the percentage of participants who have a best overall response of CR, PR, or stable disease (SD)per RESCIST 1.1. | up to approximately 2 years |
| Adverse event(AE) per Common Terminology Criteria for Adverse Events(CTCAE) 5.0 | The percentage and degree of patients who experience at least one AE, whether or not considered related to the treatment, according to CTCAE version 5.0. | up to approximately 2 years |
| Nanjing |
| China |
| Background |
| Llovet JM, Kelley RK, Villanueva A, Singal AG, Pikarsky E, Roayaie S, Lencioni R, Koike K, Zucman-Rossi J, Finn RS. Hepatocellular carcinoma. Nat Rev Dis Primers. 2021 Jan 21;7(1):6. doi: 10.1038/s41572-020-00240-3. |
| 32888471 | Background | Ochoa de Olza M, Navarro Rodrigo B, Zimmermann S, Coukos G. Turning up the heat on non-immunoreactive tumours: opportunities for clinical development. Lancet Oncol. 2020 Sep;21(9):e419-e430. doi: 10.1016/S1470-2045(20)30234-5. |
| 34593621 | Background | Pinato DJ, Murray SM, Forner A, Kaneko T, Fessas P, Toniutto P, Minguez B, Cacciato V, Avellini C, Diaz A, Boyton RJ, Altmann DM, Goldin RD, Akarca AU, Marafioti T, Mauri FA, Casagrande E, Grillo F, Giannini E, Bhoori S, Mazzaferro V. Trans-arterial chemoembolization as a loco-regional inducer of immunogenic cell death in hepatocellular carcinoma: implications for immunotherapy. J Immunother Cancer. 2021 Sep;9(9):e003311. doi: 10.1136/jitc-2021-003311. |
| 41705016 | Result | Chen JJ, Jin ZC, Zhou JW, Ding R, Tie J, Xin YJ, Zhang L, Huang M, Zhu XL, Zhou GH, Ji F, Zhu KS, Shi HB, Wu YM, Zhang WH, Yang WZ, Ding WB, Chen JZ, Ji JS, Xu AB, Zhao W, Wang Q, Dai ZY, Zheng CS, Zhao JW, Liu RB, Wu JB, Cao GS, Xing WG, Duan XH, Shao HB, Zhong BY, Zhao Y, Zhu HD, Ren ZG, Teng GJ. Transarterial chemoembolization (TACE) combined with immunotherapy and anti-angiogenic agents in intermediate-stage hepatocellular carcinoma (CHANCE2202): a target trial emulation study. EClinicalMedicine. 2026 Feb 6;92:103766. doi: 10.1016/j.eclinm.2026.103766. eCollection 2026 Feb. |
| D009369 | Neoplasms |
| D008113 | Liver Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D004066 | Digestive System Diseases |
| D008107 | Liver Diseases |