A Multicenter Registry Study on Stage III Hepatocellular Carcinoma in Unresectable CNLC Liver Cancer

NCT05660213 | Not Yet Recruiting DMC

• 1 other identifier: HELICOP
• Study Type: observational
• Target: 750
• Locations: 0 countries
• Sites: N/A

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

Conditions

Unresectable Hepatocellular Carcinoma

Keywords

Huaier granules; Unresectable hepatocellular carcinoma; curative effect; safety; Anti-PD-1/PD-L1 antibody drugs

Outcome Measures

Primary Outcomes (6)

• ORRObjective response rate (ORR)

  It defined as the proportion of subjects who achieve complete response (CR) or partial response (PR) in primary tumor imaging evaluation.

  start of treatment until 24-month follow-up

• Progression free survival (PFS)

  It defined as the time from the date the subject first receives combination therapy until the first observation of tumor progression or death from any cause.

  Start of treatment until 24-month follow-up

• Disease control rate (DCR)

  It defined as the proportion of subjects who achieve complete response (CR), partial response (PR), or disease stability (SD) as assessed by primary tumor imaging.

  Start of treatment until 24-month follow-up

• Time to Response（TTR）

  It defined as the time from the date the subject first receives combination therapy to the first observation of tumor response (CR or PR).

  Start of treatment until 24-month follow-up

• Duration of Response (DoR)

  It defined as the time from the first observation of tumor remission (CR or PR) in a subject receiving combination therapy to the first observation of tumor progression or death from any cause.

  Start of treatment until 24-month follow-up

• Overall survival (OS):

  It defined as the time from the day of randomization of patients to death from any cause.

  Start of treatment until 24-month follow-up

Secondary Outcomes (4)

• Quality of Life Score

  Start of treatment until 24-month follow-up

• The incidence and severity of adverse events (AE) and severe adverse events (SAE)

  Start of treatment until 24-month follow-up

• The incidence and severity of adverse reactions (ADR), severe adverse reactions (SADR), suspicious and unexpected severe adverse reactions (SUSAR)

  Start of treatment until 24-month follow-up

• The incidence and severity of Adverse Events of Special Concern (AESI)

  Start of treatment until 24-month follow-up

Study Arms (4)

Cohort A

Targeted drugs combined with anti-PD-1 / PD-L1 antibodies

Drug: Targeted drugs combined with anti-PD-1/PD-L1 antibodies

Cohort B

TACE (transarterial chemoembolization) combined with target immunotherapy

Drug: TACE (transarterial chemoembolization) combined with targeted/immunotherapy

Cohort C

Lenvatinib monotherapy

Drug: Lenvatinib monotherapy

Cohort D

Huaier granules combined with any of the above Cohorts for treatment

Drug: Huaier granules combined with any of the above Cohorts for treatment

Interventions

Targeted drugs combined with anti-PD-1/PD-L1 antibodies DRUG

Targeted drugs combined with anti-PD-1/PD-L1 antibodies

Cohort A

TACE (transarterial chemoembolization) combined with targeted/immunotherapy DRUG

TACE (transarterial chemoembolization) combined with targeted/immunotherapy

Cohort B

Lenvatinib monotherapy DRUG

For patients weighing less than 60 kg, the recommended daily dose of this product is 8 mg (2 capsules of 4 mg), once daily; For patients weighing ≥ 60 kg, the recommended daily dose of this product is 12 mg (3 capsules of 4 mg), once daily. Treatment should be continued until disease progression or intolerable toxic reactions occur.

Cohort C

Huaier granules combined with any of the above Cohorts for treatment DRUG

Oral administration of Huaier granules, 10g each time, 3 times a day, until the end of the study, intolerable toxicity, withdrawal from the study for any reason, or death, whichever occurs first; Or the researcher determines that there is no longer any benefit.It is recommended that the date of first use of Huaier granules be determined by the researchers, and after disease progression, the researchers and patients should jointly decide whether to continue receiving Huaier granules treatment.

Also known as: Z20000109#NMPA Approval Number#

Cohort D

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

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.

You may qualify if:

• ·≥ 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fudan University: lead
• LinkDoc Technology (Beijing) Co. Ltd.: collaborator
• Huazhong University of Science and Technology: collaborator

MeSH Terms

Interventions

Immunotherapy; Therapeutics

Intervention Hierarchy (Ancestors)

Immunomodulation; Biological Therapy

Study Officials

• Jia Fan, PhD

  Affiliated Zhongshan Hospital, Fudan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jia Fan, PhD

CONTACT

+86 021-64041990; Fan.jia@zs-hospital.sh.cn

Huichuan Sun, PhD

CONTACT

+86 021-64041990; Sun.huichuan@zs-hospital.sh.cn

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 13, 2022
• First Posted: December 21, 2022
• Study Start: August 1, 2025
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2030
• Last Updated: May 20, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share