29-Gene Liver Cancer Subtype and Immunotherapy Effectiveness

NCT07100236 | Not Yet Recruiting

• 1 other identifier: 2025-0540
• Study Type: observational
• Target: 350
• Locations: 1 country
• Sites: 13

Brief Summary

This clinical study plans to include 350 liver cancer patients from 10 tertiary hospitals nationwide, starting from August 1, 2025, at multiple centers such as the affiliated Run Run Shaw Hospital of Zhejiang University School of Medicine (the leading unit). They will be divided into a new typing queue (100 cases) and another typing queue (250 cases) using the 29 gene set algorithm. The study will collect tumor tissue samples obtained from surgical resection or puncture of patients (meeting the requirements of sample size and tumor cell proportion), perform RNA seq transcriptome sequencing, and extract patient baseline data, clinical pathological characteristics, laboratory test results, treatment information, and follow-up data from the hospital medical record system. The main objective of this study is to observe the disease progression time (TTP) and objective response rate (ORR) of patients after receiving targeted combined immunotherapy. The secondary observations include progression free survival (PFS), overall survival (OS), dynamic changes in tumor markers, liver function status, and survival after progression. The aim is to analyze the correlation between the 29 gene based new subtype of liver cancer and the efficacy of immunotherapy, providing a basis for precise diagnosis and treatment of liver cancer.

Conditions

Primary Hepatocellular Carcinoma

Keywords

Primary Hepatocellular Carcinoma; Immunotherapy; RNA-seq

Outcome Measures

Primary Outcomes (2)

• Disease Progression Time (TTP)

  Time from initiation of target-ICI therapy to first documentation of disease progression per mRECIST criteria. Progression includes: Target lesions: ≥20% increase in sum of arterial-enhancing diameters (vs baseline) + absolute increase ≥5mm; Non-target lesions: New lesions or definite progression of existing non-target lesions; Distant metastasis: New lung, bone, or lymph node metastases.

  From target-ICI therapy start, assessed at baseline, Week 8, 16, 24, progression/termination. Max 24 months through study end. Data for all time points.

• Objective Response Rate (ORR)

  Proportion of patients achieving Complete Response (CR: disappearance of arterial enhancement in all target lesions) or Partial Response (PR: ≥30% reduction in sum of target lesion diameters).

  From target-ICI therapy start, per regimen: Week 8, 16, 24, progression/termination. New regimens: same time points (reset). Max 24 months through study end. Data for all.

Secondary Outcomes (9)

• Progression - Free Survival (PFS)

  From target-ICI therapy start, assessed via imaging (baseline, every 8 weeks) and survival follow-up. Max 24 months through study end. Data for all time points.

• Overall Survival (OS)

  From target-ICI therapy start, assessed via regular follow-up. Max 24 months through study end. Survival curves; data for all time points.

• Alpha-FetoProtein (AFP)

  From target-ICI therapy start, assessed at baseline, every 4 weeks. Max 24 months. Data for all time points.

• Protein Induced by Vitamin K Absence or Antagonist II (PIVKA-II)

  From target-ICI therapy start, assessed at baseline, every 4 weeks. Max 24 months. Data for all time points.

• Child-Pugh Class

  From target-ICI therapy start, synchronized with progression. Included in 24-month data.

Study Arms (2)

Novel subtype cohort of HCC

Other: Observational study of 29 - gene - defined HCC subtypes and immunotherapy responsiveness correlation

Other HCC subtypes cohort

Other: Observational study of 29 - gene - defined HCC subtypes and immunotherapy responsiveness correlation

Interventions

Observational study of 29 - gene - defined HCC subtypes and immunotherapy responsiveness correlation OTHER

This is a non - interventional observational study. We will stratify patients with hepatocellular carcinoma (HCC) based on transcriptome sequencing of their tumor samples, specifically using a 29 - gene signature to classify them into different subtypes. Without interfering with patients' existing immunotherapy regimens (which are determined by clinical practice), we will retrospectively collect and analyze data on treatment responses. The goal is to explore the correlation between the 29 - gene - based HCC subtypes and responsiveness to immunotherapy, focusing on differences in outcomes like objective response rate (ORR) and progression - free survival (PFS) across subtypes. This study distinguishes itself by emphasizing observational analysis of pre - existing treatment patterns rather than implementing active interventions, aiming to provide insights into personalized immunotherapy for HCC through genetic subtyping.

Novel subtype cohort of HCC; Other HCC subtypes cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adult patients (≥18 years) with pathologically confirmed primary hepatocellular carcinoma, with accessible tumor samples (surgical/frozen biopsy tissues ≥3g or qualified puncture specimens). They receive targeted-immunotherapy after sample collection, with measurable lesions (RECIST 1.1). Local treatments are allowed if not overlapping with target-immunotherapy (interval ≥4 weeks). Excluded: active malignancies/organ dysfunction/uncontrolled infections/autoimmune diseases/pregnancy. All provide informed consent.

You may qualify if:

• ≥18 years old.
• Patients who visited multiple centers including Sir Run Run Shaw Hospital, Zhejiang University School of Medicine (the leading center) and were diagnosed with primary hepatocellular carcinoma by surgical pathological histology.
• They received targeted drug combined with immune checkpoint inhibitor treatment after the specimen collection time point (post - surgery or post - puncture) (that is: local treatments such as TACE, ablation, etc. are allowed before the start of targeted - immunotherapy combination treatment, but an interval of ≥4 weeks from the targeted - immunotherapy treatment is required).
• Had measurable tumor lesions at the observation start point (according to RECIST 1.1 criteria), and the tumor response status (including complete response \[CR\], partial response \[PR\], stable disease \[SD\] or progressive disease \[PD\]) could be judged by imaging examination during the observation (such as post - treatment evaluation).
• Had accessible frozen tumor tissue samples from surgical resection (sample volume ≥3g); or tumor tissue samples obtained by puncture (puncture samples need to meet the pathological diagnosis requirements, and the sample quality can support subsequent transcriptome sequencing and analysis).
• Voluntarily participate in this study and sign the informed consent form. If the subject is unable to read and sign the informed consent form due to incapacity and other reasons, their guardian shall act as the agent for the informed process and sign the informed consent form. If the subject is unable to read the informed consent form (e.g., illiterate subject), a witness shall witness the informed process and sign the informed consent form.

You may not qualify if:

• Received any local treatment during the targeted - immunotherapy combination treatment (including during treatment and within 4 weeks after treatment interruption), including:
• Transcatheter arterial chemoembolization (TACE), transcatheter arterial embolization (TAE), drug - eluting bead transcatheter arterial chemoembolization (DEB - TACE) and other vascular interventional therapies; Radiofrequency ablation, microwave ablation, cryoablation, laser ablation and other ablation therapies; Stereotactic body radiation therapy (SBRT), three - dimensional conformal radiation therapy, intensity - modulated radiation therapy and other local radiation therapies; Intratumoral injection therapy, high - intensity focused ultrasound (HIFU) and other local physical/chemical therapies.
• Local treatment was initiated before the start of targeted - immunotherapy combination treatment, and the local treatment continued into the targeted - immunotherapy treatment period (that is, there was an overlap between local treatment and targeted - immunotherapy treatment or the interval was \< 4 weeks).
• Complicated with other active malignant tumors (except for those with cured basal cell carcinoma of the skin, carcinoma in situ of the cervix, and papillary thyroid carcinoma with no recurrence for more than 5 years after surgery).
• Severe impairment of important organ functions:
• Liver function: Child - Pugh class C, or total bilirubin \> 3×ULN; Renal function: Serum creatinine \> 1.5×ULN and estimated glomerular filtration rate (eGFR) \< 50ml/min; Cardiac function: New York Heart Association (NYHA) cardiac function class Ⅲ - Ⅳ, or left ventricular ejection fraction (LVEF) \< 50%.
• Had uncontrolled active infections, including:
• Hepatitis B virus DNA \> 2000IU/ml (without receiving antiviral treatment); Hepatitis C virus RNA positive and without receiving antiviral treatment; Active tuberculosis infection, septicemia, etc.
• Had a history of autoimmune diseases and currently still needed to use systemic glucocorticoids (prednisone \> 10mg/day) or other immunosuppressive therapies.
• Pregnant or lactating women, or patients planning to become pregnant during the study.
• Had a definite history of allergy to the targeted drugs or immune checkpoint inhibitors involved in the study.
• The researcher believed that there were other factors that might affect the judgment of treatment response (such as uncontrolled hypertension, coagulation dysfunction, simultaneous use of other antineoplastic drugs during targeted - immunotherapy treatment, etc.).

Sponsors & Collaborators

• Junjie Xu: lead
• Sir Run Run Shaw Hospital: collaborator

Study Sites (13)

The First Affiliated Hospital of University of Science and Technology of China

Hefei, Anhui, 230036, China

Location

Cancer Hospital, Chinese Academy of Medical Sciences

Chaoyang, Beijing Municipality, 100021, China

Location

Fujian Provincial Hospital

Fuzhou, Fujian, 350028, China

Location

The First Affiliated Hospital of Sun Yat - sen University

Guangzhou, Guangdong, 510080, China

Location

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, 451191, China

Location

The Third Affiliated Hospital of Naval Medical University (Shanghai Eastern Hepatobiliary Surgery Hospital)

Shanghai, Shanghai Municipality, 200000, China

Location

Ruijin Hospital, Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, 200020, China

Location

Zhongshan Hospital, Fudan University

Shanghai, Shanghai Municipality, 200030, China

Location

Sir Run Run Shaw Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310000, China

Location

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, 310005, China

Location

Zhejiang People's Hospital

Hangzhou, Zhejiang, 310014, China

Location

The Second Affiliated Hospital of Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310016, China

Location

The First Affiliated Hospital of Wenzhou Medical University

Wenzhou, Zhejiang, 325000, China

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Central Study Contacts

Junjie Xu

CONTACT

86+13656688716; walter235@zju.edu.cn

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Target Duration: 1 Year
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Chief Physician

Study Record Dates

• First Submitted: July 17, 2025
• First Posted: August 3, 2025
• Study Start: August 1, 2025
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): August 1, 2027
• Last Updated: August 3, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share

Locations

CN (13)