Regional Lymph Node Metastasis and Survival Outcomes in Advanced HCC (CHANCE2421)

Regional Lymph Node Metastasis and Survival Outcomes in Advanced Hepatocellular Carcinoma Receiving Transarterial Chemoembolization and PD-(L)1 Inhibitors-based Immunotherapy

Tumor-draining lymph nodes play an important role in anti-tumor immune responses. In patients with hepatocellular carcinoma (HCC), however, the relationship between regional lymph node metastasis (LNM) and immunotherapy-based efficacy is unclear. This study aimed to evaluate whether extrahepatic LNM is associated with worse survival outcomes as compared to other metastatic sites in patients with advanced HCC.

Study Overview

• Status: Recruiting
• Conditions: Hepatocellular Carcinoma (HCC)

Detailed Description

In patients with advanced-stage hepatocellular carcinoma (HCC), previous studies showed that transarterial chemoembolization (TACE) in combination with immune checkpoint inhibitors (ICIs) and molecular target therapies exhibited better efficacy (PFS and OS) as compared to the ICIs and molecular target therapies. Besides, previous studies showed that tumor-draining lymph nodes play an important role in anti-tumor immune responses in vivo and in vitro studies. However, the relationship between regional lymph node metastasis (LNM) and immunotherapy-based efficacy is unclear. Therefore, this study aimed to evaluate whether extrahepatic LNM is associated with worse survival outcomes as compared to other metastatic sites in patients with advanced HCC who received transarterial chemoembolization (TACE) in combination with ICIs and molecular target therapies. This real-world study may provide further information on treatment selection for clinical practice and trials.

• Study Type: Observational
• Enrollment (Estimated): 300

Contacts and Locations

• Study Contact: Name: Gao-Jun Teng, M.D; Phone Number: +86-02583272121; Email: gjteng@vip.sina.com
• Study Contact Backup: Name: Hai-dong Zhu, M.D; Phone Number: +86-02583272121; Email: zhuhaidong9509@163.com

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Recruiting
      • Zhongda hospital
      • Contact: Gao-Jun Teng, M.D; Phone Number: +86-02583272121; Email: gjteng@vip.sina.com
    • Nanjing, Jiangsu, China
      • Completed
      • Zhongda hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Probability Sample

Study Population

Patients with metastatic HCC who received TACE in combination with PD-1/PD-L1 inhibitors and molecular target therapies under real-world practice conditions

Description

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;
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 (within 3 months);
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;
3. Child-Pugh C or PS > 2 or Severe hepatic encephalopathy

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival(OS)	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
PFS per Modified Response Evaluation Criteria in Solid Tumors (mRECIST)	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
Objective response rate(ORR) per RESCIST 1.1	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
ORR per mRECIST	ORR is defined as the proportion of patients with a documented CR or PR per mRECIST.	up to approximately 2 years

Collaborators and Investigators

• Sponsor: Zhongda Hospital
• Investigators: Principal Investigator: Gao-jun Teng, M.D, Zhongda hospital, Southeast university, Nanjing, China

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2018
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): July 1, 2025

Study Registration Dates

• First Submitted: March 10, 2025
• First Submitted That Met QC Criteria: March 10, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 10, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: hepatocellular carcinoma; lymph node metastasis; transarterial chemoembolization; immune checkpoint inhibitors; molecular target therapies
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Liver Neoplasms; Neoplastic Processes; Carcinoma; Carcinoma, Hepatocellular; Neoplasm Metastasis; Lymphatic Metastasis
• Other Study ID Numbers: CHANCE2421

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No