TACE in Combination With PD-1/PD-L1 Inhibitors and Molecular Target Therapies for Advanced HCC

Hepatocellular Carcinoma Clinical Trial

— CHANCE2201  

Official title:

Efficacy and Safety of Transarterial Chemoembolization in Combination With PD-1/PD-L1 Inhibitors and Molecular Target Therapies(VEGF-TKI/Bevacizumab) for Advanced Stage HCC

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05332821
• Other study ID #: CHANCE2201
• Status: Recruiting
• Start date: December 28, 2022
• Est. completion date: August 31, 2023

Study information

• Verified date: December 2022
• Source: Zhongda Hospital
• Contact: Gao-Jun Teng, M.D.
• Phone: +86-02583272121
• Email: gjteng[@]vip.sina.com
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

The purpose of this study is to evaluate the safety and efficacy of transarterial chemoembolization (TACE) in combination with immune checkpoint inhibitors (ICIs) and molecular target therapies in patients with advanced-stage hepatocellular carcinoma (HCC).

Description:

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 immune checkpoint inhibitors (ICIs) and molecular target therapies(including, VEGF-TKI/ bevacizumab) in patients with advanced-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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 474
• Est. completion date: August 31, 2023
• Est. primary completion date: August 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Has a diagnosis of HCC confirmed by radiology, histology, or cytology;

2. Barcelona Clinic Liver Cancer (BCLC) stage C with the presence of extrahepatic spread and/or macrovascular invasion;

3. Has not received any previous systemic therapy for HCC (including chemotherapy, molecularly targeted therapy, immunotherapy);

4. Both PD-1/PD-L1 inhibitors and anti-angiogenesis drugs patients received only include marketed drugs but are not limited to HCC approval;

5. TACE was performed after the first PD-1/PD-L1 inhibitor/anti-angiogenic drug treatment or before treatment;

6. Received at least 1 cycle of PD-1/PD-L1 inhibitor/anti-angiogenic drug combination therapy after TACE treatment;

7. Has repeated measurable intrahepatic lesions;

Exclusion Criteria:

1. Cholangiocarcinoma, fibrolamellar, sarcomatoid hepatocellular carcinoma, and mixed hepatocellular/cholangiocarcinoma subtypes(confirmed by histology, or pathology) are not eligible;

2. Unable to meet criteria of combination timeframe described above;

Related Conditions & MeSH terms

• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma

Intervention

Drug:
• PD-1/PD-L1 inhibitors+VEGF-TKI/bevacizumab
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.

Procedure:
• TACE
TACE: cTACE (conventional TACE) or dTACE (drug-eluting beads TACE);

Locations

Country	Name	City	State
China	Gao-Jun Teng	Nanjing
China	Zheng-Gang Ren	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Zhongda Hospital

Country where clinical trial is conducted

China, 

References & Publications (4)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Secondary	Progression free survival(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
Secondary	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
Secondary	Objective response rate(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
Secondary	Duration of Response (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
Secondary	Disease Control Rate (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
Secondary	ORR per mRECIST	The ORR is defined as the proportion of patients with a documented CR or PR per mRECIST.	up to approximately 2 years
Secondary	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
Secondary	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
Secondary	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