Therapeutic ResistAnce and Clonal Evolution Assessed With Liquid Biopsy in ICIs Treated Primary Liver Cancer

To evaluate the predictive value of ctDNA in response, relapse for liver cancer patients treated with immune checkpoint inhibitors

Study Overview

• Status: Withdrawn
• Conditions: Hepatocellular Carcinoma; Primary Liver Cancer; Intrahepatic Cholangiocarcinoma; Combined Hepatocellular-cholangiocarcinoma
• Intervention / Treatment: Other: Observation

Detailed Description

In the study, 300 advanced primery liver cancer patients who received immune checkpoint inhibitors at first-line setting (N=200) or second-line setting (N=100) will be recruited. By analyzing the ctDNA and peripheral blood mononuclear cell (PBMC) collected before and after the first cycle of ICI treatment, the dynamic changes of bTMB, ctDNA and the composition of immune cells will be detected. Combined with the tumor markers AFP, DCP and CA19-9, a noninvasive multiparameter model will be developed.

• Study Type: Observational

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100053
      • Xuanwu Hospital Capital Medical University
    • Beijing, Beijing, China, 100730
      • Beijing Hospital
  • Chongqing
    • Chongqing, Chongqing, China, 401147
      • Institute of Hepatopancreatobiliary Surgery, Chongqing General Hospital, University of Chinese Academy of Sciences (UCAS)
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Tongji Hospital affiliated to Tongji Medical College of Huazhong University
  • Shanghai
    • Shanghai, Shanghai, China, 200438
      • Eastern Hepatobiliary Surgery Hospital, Second Military Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Primary liver cancer including hepatocellular carcinoma, intrahepatic cholangiocarcinoma and combined hepatocellular-cholangiocarcinoma

Description

Inclusion Criteria:

• Primary liver cancer diagnosed according to the clinical diagnostic criteria, or histopathological or cytological examination;
• 18-80 years old, no limit on gender;
• ECOG performance status of 0-2, with expected survival time of more than 12 weeks;
• According to RECIST V1.1, there must be at least one measurable lesion;
• Patients who are suitable for ICIs treatment and willing to comply with required protocols and give permission to use the data for clinical research and products development;
• Patients who join the study voluntarily, sign a consent form, have good compliance, and comply with follow-up.

Exclusion Criteria:

• Patients with other primary cancers;
• Patients with a severe parenchymal disease and unable to accept ICIs treatment;
• Patients with a psychiatric disorder and unable to comply with this study;
• Patients with symptomatic brain metastasis, anticipated complications or cognitive disorders that are associated with brain metastasis;
• Adverse events related to prior anti-tumor treatment (except for hair loss of any grade) did not return to grade 1 or better;
• History of cells or organ transplantation;
• History of hypersensitivity to the drug administered in this study or contrast media for CT and MRI;
• Patients who accepted hepatic local therapy (including ablation therapy, percutaneous injection of ethanol or acetic acid (PEI/PAI), high-intensity focused ultrasound (HIFU), transarterial chemoembolization (TACE)) within 14 days prior to initiation of the study;
• Other reasons that the researchers think not suitable for ICIs treatment

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS: Progression-free survival	The time length from the date of randomization to any of the following events: disease progression or death from any cause.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR: Objective Response Rate	The proportion of patients with complete response or partial response.	24 months
OS: Overall Survival	The time length from the date of randomization to the date of death.	24 months
TTD: Time to Treatment Discontinuation	The time length from the date of randomization to the date of treatment discontinuation.	24 months

Collaborators and Investigators

• Sponsor: Geneplus-Beijing Co. Ltd.
• Collaborators: Eastern Hepatobiliary Surgery Hospital
• Investigators: Principal Investigator: Feng Shen, MD PhD, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University

Study record dates

Study Major Dates

• Study Start (Actual): December 20, 2021
• Primary Completion (Actual): March 17, 2023
• Study Completion (Actual): March 17, 2023

Study Registration Dates

• First Submitted: March 14, 2022
• First Submitted That Met QC Criteria: March 14, 2022
• First Posted (Actual): March 23, 2022

Study Record Updates

• Last Update Posted (Actual): February 23, 2024
• Last Update Submitted That Met QC Criteria: February 21, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Liquid biopsy; Immune Checkpoint Inhibitor; Next Generation Sequencing (NGS); Whole Transcriptome Sequencing
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Cholangiocarcinoma; Liver Neoplasms
• Other Study ID Numbers: HisPower-Lib 002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No