Clinical trial NCT05332496: TACE in Combination With PD-1/PD-L1 Inhibitors and Molecular Target Therapies for Intermediate HCC
Official title: Efficacy and Safety of Transarterial Chemoembolization in Combination With PD-1/PD-L1 Inhibitors and Molecular Target Therapies(VEGF-TKI/Bevacizumab) for Intermediate Stage HCC
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Hepatocellular Carcinoma
Keywords: hepatocellular carcinoma
transarterial chemoembolization
immune checkpoint inhibitors
molecular target therapies
Intermediate stage
Lead sponsor: Zhongda Hospital
Sponsor class: OTHER
First posted: 2022-04-18
Enrollment: 220
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with intermediate HCC who received TACE in combination with PD-1/PD-L1 inhibitors and molecular target therapies under real-world practice conditions.

Brief summary: 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).

Detailed 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 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.

Eligibility criteria: Inclusion Criteria:

1. Has a diagnosis of HCC confirmed by radiology, histology, or cytology;
2. Barcelona Clinic Liver Cancer (BCLC) stage B, without the presence of extrahepatic spread and/or macrovascular invasion;
3. Has not received any previous TACE/HAIC and 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 according to mRECIST;

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;

Primary outcomes:
measure: Progression free survival(PFS) per Modified Response Evaluation Criteria in Solid Tumors (mRECIST)
timeFrame: up to approximately 2 years
measure: Overall Survival(OS)
timeFrame: up to approximately 2 years
Secondary outcomes:
measure: PFS per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
timeFrame: up to approximately 2 years
measure: Objective response rate(ORR) per mRECIST
timeFrame: up to approximately 2 years
measure: Duration of Response (DOR) per mRECIST
timeFrame: up to approximately 2 years
measure: Disease Control Rate (DCR) per mRECIST
timeFrame: up to approximately 2 years
measure: ORR per RESCIST 1.1
timeFrame: up to approximately 2 years
measure: DOR per RESCIST 1.1
timeFrame: up to approximately 2 years
measure: DCR per RESCIST 1.1
timeFrame: up to approximately 2 years
measure: Adverse event(AE) per Common Terminology Criteria for Adverse Events(CTCAE) 5.0
timeFrame: up to approximately 2 years
Other outcomes:
Locations:
city: Nanjing
country: China
facility: Gao-Jun Teng
city: Nanjing
country: China
facility: Zheng-Gang Ren
Study officials:
affiliation: Zhongda hospital, Southeast university, Nanjing, China
name: Gao-Jun Teng, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
name: Zheng-Gang Ren, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
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.
citation: 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.
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.
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.