Clinical trial NCT05660213: A Multicenter Registry Study on Stage III Hepatocellular Carcinoma in Unresectable CNLC Liver Cancer
Official title: A Multicenter Registry Study on the Efficacy and Safety of Different Treatment Regimens for Unresectable CNLC Liver Cancer Stage III Hepatocellular Carcinoma
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Unresectable Hepatocellular Carcinoma
Keywords: Huaier granules
Unresectable hepatocellular carcinoma
curative effect
safety
Anti-PD-1/PD-L1 antibody drugs
Lead sponsor: Fudan University
Sponsor class: OTHER
Collaborators: name: LinkDoc Technology (Beijing) Co. Ltd.
name: Huazhong University of Science and Technology
First posted: 2022-12-21
Enrollment: 750
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: During the whole study period, a total of 750 patients in the selected research centers from December 2024 to December 2025 were planned to be recruited consecutively, including 150 in cohort a, 150 in cohort B, 150 in cohort C, and 300 in cohort D. A single subject was visited every 8 weeks after enrollment until the diagnosis and treatment mode changed, disease progression or the patient withdrew from the study or died for any reason, whichever occurred first. The maximum duration of a single subject's total visit shall not exceed 24 months.

Brief summary: This study is a multicenter, registered research aimed at evaluating the efficacy of different treatment regimens in the treatment of unresectable CNLC liver cancer stage III hepatocellular carcinoma

Detailed description: This study is a multicenter, observational, natural cohort registration study. We plan to continuously include 750 subjects diagnosed with unresectable CNLC stage III hepatocellular carcinoma (HCC) at selected research centers. According to the actual clinical diagnosis and treatment plan of patients, the following treatment modes will be included in the Cohort of patients:

Cohort A: Targeted drugs combined with anti-PD-1/PD-L1 antibodies Cohort B: TACE (transarterial chemoembolization) combined with targeted/immunotherapy Cohort C: Lenvatinib monotherapy Cohort D: Huaier granules combined with any of the above Cohorts for treatment Throughout the entire study period, it is planned to recruit patients who have visited the selected research center within 12 months (December 2024 to December 2025). Each individual subject will be followed up every 8 weeks until the diagnosis and treatment mode changes, disease progression progresses, or the patient withdraws from the study or dies for any reason, whichever occurs first.

Eligibility criteria: Inclusion Criteria:

·≥ 18 years old;

* Diagnosed as unresectable hepatocellular carcinoma through histopathological and/or cytological examination, or meeting the clinical diagnostic criteria for hepatocellular carcinoma in the 2022 edition of the guidelines for the diagnosis and treatment of primary liver cancer;
* CNLC liver cancer stage III;
* Liver function Child Pugh A or B grade 7 points;
* Has not received systematic treatment in the past;
* Patients with active HBV infection who meet one of the following conditions can be enrolled: ① Within 28 days before enrollment, the patient's HBV DNA is less than 500 IU/mL. If they have received anti HBV treatment, they need to continue their original antiviral treatment; If anti HBV treatment has not been received, it is necessary to receive anti HBV treatment throughout the entire course of medication (according to local treatment standards; for example, entecavir); ② For patients with HBV DNA\>500 IU/mL and who have not received antiviral therapy, they must receive at least 7 days of antiviral therapy (according to local treatment standards; for example, entecavir) before enrollment in this study, and are willing to continue receiving antiviral therapy during the study. Before enrollment, the serum HBV-DNA virus should be retested to decrease by more than 1 log value For patients with HBV DNA\>500 IU/mL and who have received antiviral therapy, they must receive at least 7 days of antiviral therapy (according to local treatment standards; for example, entecavir) before enrollment in this study, and are willing to continue receiving antiviral therapy during the study. Serum HBV-DNA virus levels should be retested before enrollment;
* Active HCV infected individuals with stable disease status after treatment;
* At least one tumor lesion available for evaluation;
* Clear consciousness, language expression ability or reading ability, able to communicate normally, and cooperate to complete the questionnaire evaluation;
* Voluntarily join this study and sign an informed consent form.

Exclusion Criteria:

* Simultaneously having two or more active primary malignant tumors;
* Portal vein cancer thrombus invades the superior mesenteric vein;
* Received radiation therapy within the past 4 weeks;
* Expected survival time is less than 3 months;
* Pregnant or lactating women or those planning to conceive;
* Coagulation dysfunction (INR\>2.0, PT\>16 s) or diseases with a strong likelihood of bleeding (including but not limited to esophageal and/or gastric variceal bleeding, active ulcers, uncontrolled hypertension);
* Refusing to cooperate with follow-up visits;
* Other reasons led the researchers to believe that it was not suitable to participate in this study.

Primary outcomes:
measure: ORRObjective response rate (ORR)
timeFrame: start of treatment until 24-month follow-up
measure: Progression free survival (PFS)
timeFrame: Start of treatment until 24-month follow-up
measure: Disease control rate (DCR)
timeFrame: Start of treatment until 24-month follow-up
measure: Time to Response（TTR）
timeFrame: Start of treatment until 24-month follow-up
measure: Duration of Response (DoR)
timeFrame: Start of treatment until 24-month follow-up
measure: Overall survival (OS):
timeFrame: Start of treatment until 24-month follow-up
Secondary outcomes:
measure: Quality of Life Score
timeFrame: Start of treatment until 24-month follow-up
measure: The incidence and severity of adverse events (AE) and severe adverse events (SAE)
timeFrame: Start of treatment until 24-month follow-up
measure: The incidence and severity of adverse reactions (ADR), severe adverse reactions (SADR), suspicious and unexpected severe adverse reactions (SUSAR)
timeFrame: Start of treatment until 24-month follow-up
measure: The incidence and severity of Adverse Events of Special Concern (AESI)
timeFrame: Start of treatment until 24-month follow-up
Other outcomes:
Locations:
Study officials:
affiliation: Affiliated Zhongshan Hospital, Fudan University
name: Jia Fan, PhD
role: PRINCIPAL_INVESTIGATOR
References: