CHANCE2201: TACE in Combination With PD-1/PD-L1 Inhibitors and Molecular Target Therapies for Advanced HCC

Sponsor

Zhongda Hospital (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05332821

Collaborator

(none)

474

Enrollment

16.6

Anticipated Duration (Months)

Study Details

Study Description

Brief 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).

Condition or Disease	Intervention/Treatment	Phase
Hepatocellular Carcinoma	Drug: PD-1/PD-L1 inhibitors+VEGF-TKI/bevacizumab Procedure: TACE

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 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.

Study Design

Study Type:

Observational [Patient Registry]

Anticipated Enrollment :

474 participants

Observational Model:

Cohort

Time Perspective:

Other

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

Anticipated Study Start Date :

Apr 13, 2022

Anticipated Primary Completion Date :

Aug 31, 2022

Anticipated Study Completion Date :

Aug 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
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；	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);
Control group: PD-1/PD-L1 inhibitors+VEGF-TKI/bevacizumab The interval between first use PD-1/PD-L1 inhibitors and anti-angiogenesis drugs ≤1 week；	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.

Arm

Intervention/Treatment

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；

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);

Control group: PD-1/PD-L1 inhibitors+VEGF-TKI/bevacizumab

The interval between first use PD-1/PD-L1 inhibitors and anti-angiogenesis drugs ≤1 week；

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

Outcome Measures

Primary Outcome Measures

Overall Survival(OS) [up to approximately 2 years]
The OS is defined as the time from the initiation of any combination treatment to death due to any cause.

Secondary Outcome Measures

Progression free survival(PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) [up to approximately 2 years]
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.
PFS per Modified Response Evaluation Criteria in Solid Tumors (mRECIST) [up to approximately 2 years]
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.
Objective response rate(ORR) per RESCIST 1.1 [up to approximately 2 years]
The ORR is defined as the proportion of patients with a documented complete response(CR) or partial response(PR) per RECIST 1.1.
Duration of Response (DOR) per RESCIST 1.1 [up to approximately 2 years]
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.
Disease Control Rate (DCR) per RESCIST 1.1 [up to approximately 2 years]
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.
ORR per mRECIST [up to approximately 2 years]
The ORR is defined as the proportion of patients with a documented CR or PR per mRECIST.
DOR per mRECIST [up to approximately 2 years]
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.
DCR per mRECIST [up to approximately 2 years]
DCR is defined as the percentage of participants who have a best overall response of CR, PR, or stable disease (SD) per mRECIST.
Adverse event(AE) per Common Terminology Criteria for Adverse Events(CTCAE) 5.0 [up to approximately 2 years]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Has a diagnosis of HCC confirmed by radiology, histology, or cytology;
Barcelona Clinic Liver Cancer (BCLC) stage C with the presence of extrahepatic spread and/or macrovascular invasion;
Has not received any previous systemic therapy for HCC (including chemotherapy, molecularly targeted therapy, immunotherapy);
Both PD-1/PD-L1 inhibitors and anti-angiogenesis drugs patients received only include marketed drugs but are not limited to HCC approval;
TACE was performed after the first PD-1/PD-L1 inhibitor/anti-angiogenic drug treatment or before treatment;
Received at least 1 cycle of PD-1/PD-L1 inhibitor/anti-angiogenic drug combination therapy after TACE treatment；
Has repeated measurable intrahepatic lesions;

Exclusion Criteria:

Cholangiocarcinoma, fibrolamellar, sarcomatoid hepatocellular carcinoma, and mixed hepatocellular/cholangiocarcinoma subtypes(confirmed by histology, or pathology) are not eligible;
Unable to meet criteria of combination timeframe described above;

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

Zhongda Hospital

Investigators

Principal Investigator: 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