Primary Hepatocellular CarcinomaNCT07100236
29-Gene Liver Cancer Subtype and Immunotherapy Effectiveness
An observational study of Primary Hepatocellular Carcinoma, run by Junjie Xu at 13 sites in China.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Primary Hepatocellular Carcinoma
- What is being tested?
- Observational study of 29 - gene - defined HCC subtypes and immunotherapy responsiveness correlation
- How many people
- 350 participants
- Where
- 13 sitesChina
- Study dates
- 1 Aug 2025to 1 Aug 2027
- How long will I take part?
- 1 Year
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- ≥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.
Who cannot join
- 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%.
Show all 12Show fewer
- 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.).
Trial locations and contacts
13 sites in 1 country. Contact the study team or a site near you to ask about taking part.
13 sites in 1 country
China13 sites
Cancer Hospital, Chinese Academy of Medical Sciences
Chaoyang, Beijing Municipality, 100021
Hongguang Wang, Dr., 86+13717659265
Fujian Provincial Hospital
Fuzhou, Fujian, 350028
Shi Chen, Dr., 86+15059186186
The First Affiliated Hospital of Sun Yat - sen University
Guangzhou, Guangdong, 510080
Wei Chen, Dr., 86+13416476268
Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
Hangzhou, Zhejiang, 310000
Junjie Xu, 86+13656688716, walter235@zju.edu.cn
Yangtao Xue, 86+13676738276, 22318190@zju.edu.cn
Zhejiang Cancer Hospital
Hangzhou, Zhejiang, 310005
Yuhua Zhang, Dr., 86+13588033123, zhangyuhua1013@126.com
Zhejiang People's Hospital
Hangzhou, Zhejiang, 310014
Fangqiang Wei, Dr., 86+13732207136
The Second Affiliated Hospital of Zhejiang University School of Medicine
Hangzhou, Zhejiang, 310016
Yuan Ding, 86+18858101960, dingyuan@zju.edu.cn
The First Affiliated Hospital of University of Science and Technology of China
Hefei, Anhui, 230036
Dalong Yin, Dr., 86+18110984879, doctoryin@ustc.edu.cn
The Third Affiliated Hospital of Naval Medical University (Shanghai Eastern Hepatobiliary Surgery Hospital)
Shanghai, Shanghai Municipality, 200000
Tian Yang, Dr., 86+18917015805, yangtianehbh@smmu.edu.cn
Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
Shanghai, Shanghai Municipality, 200020
Guodong Zhao, Dr., 86+13581721783
Zhongshan Hospital, Fudan University
Shanghai, Shanghai Municipality, 200030
Qiang Gao, Dr., 86+13816266282, gaoqiang@fudan.edu.cn
The First Affiliated Hospital of Wenzhou Medical University
Wenzhou, Zhejiang, 325000
Gang Chen, Dr., 86+13616619566, chen.gang@wmu.edu.cn
The First Affiliated Hospital of Zhengzhou University
Zhengzhou, Henan, 451191
Zhengfeng Wang, Dr., 86+13633827566
About this study
Official title: Identification of a Novel 29-Gene-Based Subtype of Hepatocellular Carcinoma and Its Correlation With Immunotherapy Efficacy
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.
Read the detailed description
This is a multicenter cohort study aimed at exploring the correlation between a novel 29-gene-based subtype of primary hepatocellular carcinoma (HCC) and response to immunotherapy, with the goal of verifying that this new subtype exhibits higher responsiveness to immunotherapy.
Study Population: A total of 350 patients with pathologically confirmed primary HCC will be enrolled from 10 tertiary hospitals across China, with Sir Run Run Shaw Hospital, Zhejiang University School of Medicine as the leading center. Eligibility criteria include: age ≥ 18 years; having measurable tumor lesions per RECIST 1.1; receiving targeted therapy combined with immune checkpoint inhibitors (ICI) after sample collection (with ≥4 weeks interval from prior local treatments if any); availability of qualified tumor samples (≥3g frozen surgical tissues or biopsy specimens sufficient for transcriptome sequencing); and provision of informed consent. Patients will be excluded if they have overlapping local treatments (e.g., TACE, ablation, radiotherapy) during or within 4 weeks of target-ICI combination therapy, concurrent active malignancies (except cured basal cell carcinoma, etc.), severe organ dysfunction (e.g., Child-Pugh Class C liver function, NYHA Class Ⅲ-Ⅳ cardiac function), or other factors interfering with efficacy assessment as judged by investigators.
Study Procedures:
Sample Processing and Subtyping: Tumor samples will undergo RNA sequencing using the Illumina HiSeq platform (outsourced to Hangzhou DIAN Diagnostics company). After quality control, alignment, and quantification, hierarchical clustering based on a 29-gene signature will classify patients into a "novel subtype cohort" (unmatchable to TCGA HCC clusters) and an "other subtypes cohort".
Data Collection: Clinical data will be extracted from electronic medical records, including baseline characteristics (age, gender, Child-Pugh classification), treatment details (target-ICI regimens, doses, cycles), imaging evaluations (enhanced CT/MRI for tumor response assessment per mRECIST), and follow-up data (survival status, tumor marker dynamics).
Outcome Measures:
Primary Outcomes: Time to Progression (TTP, defined as the interval from initiation of target-ICI therapy to first progression per mRECIST) and 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]). ORR will be assessed at Weeks 8, 16, 24, or progression for each line of therapy; if regimens are changed due to poor efficacy, assessment timelines will be reset for the new regimen, with CR/PR status strictly linked to the corresponding regimen.
Secondary Outcomes: Progression-Free Survival (PFS), Overall Survival (OS), dynamic changes in tumor markers (AFP, PIVKA-II), liver function status at progression, and Post-Progression Survival (PPS).
Statistical Analysis: Group differences will be compared using appropriate tests (t-test, ANOVA, Mann-Whitney U test, Chi-square test, or Fisher's exact test as applicable). Survival analyses (TTP, PFS, OS, PPS) will employ the Kaplan-Meier method with Log-rank tests, and Cox proportional hazards models will evaluate the impact of 29-gene subtyping on progression risk. A p-value < 0.05 will be considered statistically significant.
This study aims to provide evidence for precision immunotherapy in HCC by clarifying the association between the 29-gene-based subtype and immunotherapeutic efficacy.
- Conditions
- Primary Hepatocellular Carcinoma
- Being tested
- Observational study of 29 - gene - defined HCC subtypes and immunotherapy responsiveness correlation
- Keywords
- Primary Hepatocellular Carcinoma, Immunotherapy, RNA-seq
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Observational study of 29 - gene - defined HCC subtypes and immunotherapy responsiveness correlationOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Novel subtype cohort of HCC | Not described Receives: Other: Observational study of 29 - gene - defined HCC subtypes and immunotherapy responsiveness correlation | |
| Other HCC subtypes cohort | Not described Receives: Other: Observational study of 29 - gene - defined HCC subtypes and immunotherapy responsiveness correlation |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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).
Measured: 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)
Time from target-ICI therapy start to first disease progression (per mRECIST) or any-cause death (whichever occurs first).
Measured: 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)
Time from target-ICI therapy start to any-cause death; lost-to-follow-up patients censored at last follow-up.
Measured: 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)
Monitoring of alpha-fetoprotein (AFP) for ≥20% increase (vs baseline) lasting ≥4 weeks, combined with imaging to predict progression risk.
Measured: 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)
Monitoring of protein induced by vitamin K absence/antagonist-II (PIVKA-II) for ≥20% increase (vs baseline) lasting ≥4 weeks, combined with imaging to predict progression risk.
Measured: From target-ICI therapy start, assessed at baseline, every 4 weeks. Max 24 months. Data for all time points.
Child-Pugh Class
At disease progression, collect Child-Pugh class data. Compare with baseline (excluding drug-induced liver injury) to analyze direct impact of tumor progression on liver function impairment.
Measured: From target-ICI therapy start, synchronized with progression. Included in 24-month data.
Total Bilirubin
At disease progression, collect total bilirubin data. Compare with baseline (excluding drug-induced liver injury) to analyze direct impact of tumor progression on liver function impairment.
Measured: From target-ICI therapy start, synchronized with progression. Included in 24-month data.
Albumin
At disease progression, collect albumin data. Compare with baseline (excluding drug-induced liver injury) to analyze direct impact of tumor progression on liver function impairment.
Measured: From target-ICI therapy start, synchronized with progression. Included in 24-month data.
Internationalnormalizedratio (INR)
At disease progression, collect INR (International Normalized Ratio) data. Compare with baseline (excluding drug-induced liver injury) to analyze direct impact of tumor progression on liver function impairment.
Measured: From target-ICI therapy start, synchronized with progression. Included in 24-month data.
Post-Progression Survival (PPS)
Time from disease progression to death or study end. Record post-progression treatments (targeted drug change, local therapy) and analyze impact on survival.
Measured: From disease progression (post target-ICI start), follow-up post-progression. Max 24 months post-progression through study end. Data for all time points.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Aug 2025
- Study start1 Aug 2025 (estimated)
- Primary completion1 May 2027 (estimated)
- Study completion1 Aug 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Primary Hepatocellular CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 350 participants (estimated)
- Target duration
- 1 Year
Sponsor and investigators
- Lead sponsor
- Junjie Xu
- Sponsor type
- University, hospital or other
- Collaborators
- Sir Run Run Shaw Hospital
- Responsible party
- Sponsor-investigator, Junjie Xu, Sir Run Run Shaw Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07100236
- Sponsor's protocol ID
- 2025-0540
- Status last verified
- Jul 2025
- First submitted
- 17 Jul 2025
- Last updated
- 3 Aug 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 3 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Identification of a Novel 29-Gene-Based Subtype of Hepatocellular Carcinoma and Its Correlation With Immunotherapy Efficacy
- ClinicalTrials.gov ID
- NCT07100236
- Acronym / sponsor ID
- 2025-0540
- Conditions
- Primary Hepatocellular Carcinoma
- Keywords
- Primary Hepatocellular Carcinoma, Immunotherapy, RNA-seq
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 350 participants (estimated)
- Lead sponsor
- Junjie XuUniversity, hospital or other
- Collaborators
- Sir Run Run Shaw Hospital
- Study start
- 1 Aug 2025 (estimated)
- Primary completion
- 1 May 2027 (estimated)
- Study completion
- 1 Aug 2027 (estimated)
- First posted
- 3 Aug 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is a multicenter cohort study aimed at exploring the correlation between a novel 29-gene-based subtype of primary hepatocellular carcinoma (HCC) and response to immunotherapy, with the goal of verifying that this new subtype exhibits higher responsiveness to immunotherapy.
Study Population: A total of 350 patients with pathologically confirmed primary HCC will be enrolled from 10 tertiary hospitals across China, with Sir Run Run Shaw Hospital, Zhejiang University School of Medicine as the leading center. Eligibility criteria include: age ≥ 18 years; having measurable tumor lesions per RECIST 1.1; receiving targeted therapy combined with immune checkpoint inhibitors (ICI) after sample collection (with ≥4 weeks interval from prior local treatments if any); availability of qualified tumor samples (≥3g frozen surgical tissues or biopsy specimens sufficient for transcriptome sequencing); and provision of informed consent. Patients will be excluded if they have overlapping local treatments (e.g., TACE, ablation, radiotherapy) during or within 4 weeks of target-ICI combination therapy, concurrent active malignancies (except cured basal cell carcinoma, etc.), severe organ dysfunction (e.g., Child-Pugh Class C liver function, NYHA Class Ⅲ-Ⅳ cardiac function), or other factors interfering with efficacy assessment as judged by investigators.
Study Procedures:
Sample Processing and Subtyping: Tumor samples will undergo RNA sequencing using the Illumina HiSeq platform (outsourced to Hangzhou DIAN Diagnostics company). After quality control, alignment, and quantification, hierarchical clustering based on a 29-gene signature will classify patients into a "novel subtype cohort" (unmatchable to TCGA HCC clusters) and an "other subtypes cohort".
Data Collection: Clinical data will be extracted from electronic medical records, including baseline characteristics (age, gender, Child-Pugh classification), treatment details (target-ICI regimens, doses, cycles), imaging evaluations (enhanced CT/MRI for tumor response assessment per mRECIST), and follow-up data (survival status, tumor marker dynamics).
Outcome Measures:
Primary Outcomes: Time to Progression (TTP, defined as the interval from initiation of target-ICI therapy to first progression per mRECIST) and 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]). ORR will be assessed at Weeks 8, 16, 24, or progression for each line of therapy; if regimens are changed due to poor efficacy, assessment timelines will be reset for the new regimen, with CR/PR status strictly linked to the corresponding regimen.
Secondary Outcomes: Progression-Free Survival (PFS), Overall Survival (OS), dynamic changes in tumor markers (AFP, PIVKA-II), liver function status at progression, and Post-Progression Survival (PPS).
Statistical Analysis: Group differences will be compared using appropriate tests (t-test, ANOVA, Mann-Whitney U test, Chi-square test, or Fisher's exact test as applicable). Survival analyses (TTP, PFS, OS, PPS) will employ the Kaplan-Meier method with Log-rank tests, and Cox proportional hazards models will evaluate the impact of 29-gene subtyping on progression risk. A p-value < 0.05 will be considered statistically significant.
This study aims to provide evidence for precision immunotherapy in HCC by clarifying the association between the 29-gene-based subtype and immunotherapeutic efficacy.
Study design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Target follow-up
- 1 Year
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (6 listed)
- ≥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).
Key exclusion criteria (12 listed)
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Observational study of 29 - gene - defined HCC subtypes and immunotherapy responsiveness correlationThis 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. | Other | Novel subtype cohort of HCC, Other HCC subtypes cohort |
Primary outcome
Disease Progression Time (TTP)
Time frame: 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.
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.
Objective Response Rate (ORR)
Time frame: 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.
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).
9 secondary outcomes
Progression - Free Survival (PFS)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: From target-ICI therapy start, assessed at baseline, every 4 weeks. Max 24 months. Data for all time points.
Child-Pugh Class
Time frame: From target-ICI therapy start, synchronized with progression. Included in 24-month data.
Total Bilirubin
Time frame: From target-ICI therapy start, synchronized with progression. Included in 24-month data.
Albumin
Time frame: From target-ICI therapy start, synchronized with progression. Included in 24-month data.
Internationalnormalizedratio (INR)
Time frame: From target-ICI therapy start, synchronized with progression. Included in 24-month data.
Post-Progression Survival (PPS)
Time frame: From disease progression (post target-ICI start), follow-up post-progression. Max 24 months post-progression through study end. Data for all time points.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Aug 2025.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
13 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Primary Hepatocellular Carcinoma, run by Junjie Xu at 13 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 3 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Junjie Xu (86+13656688716, walter235@zju.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Disease Progression Time (TTP) (time frame: 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.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Aug 2025.