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Icaritin Soft Capsule Combined With Lenvatinib and TACE for the Treatment of Hepatocellular Carcinoma

Primary Purpose

Hepatocellular Carcinoma

Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
TACE(transcatheter arterial chemoembolization)
lenvatinib
Icaritin soft capsules
Sponsored by
Zhejiang Cancer Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatocellular Carcinoma focused on measuring Hepatocellular carcinoma; Icaritin soft capsules;TACE; lenvatinib

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Between the ages of 18 and 80; Patients with histological/cytological confirmed hepatocellular carcinoma. HCC patients eligible for China liver cancer staging (CNLC) Stage IIIa, which cannot be resectable, are not suitable for radical treatment. According to the RECIST v1.1 standard, there must be at least one measurable lesion on the upper abdominal enhanced CT or MRI. Child-Pugh grade A or B; ECOG physical condition score is 0 or 1; Suitable for the indications of TACE surgery and chemotherapy drugs prescribed in advance by the research center, without any contraindications. Regular antiviral therapy should be given if HBV or HCV infection is present. Life expectancy is more than 3 months Able to swallow and absorb oral tablets; Appropriate organ function with the following laboratory test values obtained within 7 days prior to therapeutic use: (hemoglobin value ≥80g/L, neutrophil count ≥2.5×109/L, platelet count ≥75×109/L, serum total bilirubin ≤2× upper limit of normal (UNL), aspartic transferase ≤2×UNL, alanine transferase ≤3×UNL, serum creatinine ≤1.5×UNL) Manageable blood pressure Women of childbearing age must already be using reliable contraception or have had a negative pregnancy test (serum or urine) within 7 days prior to enrollment and be willing to use an effective method of contraception during the trial period and within 2 months after the last drug administration. Male subjects whose partners are women of childbearing age should use effective methods of contraception during the trial period and within 2 months after the last dose; The subjects voluntarily joined the study, signed the informed consent, had good compliance, and cooperated with follow-up. Exclusion Criteria: Formation of portal vein main cancer thrombus or extensive cancer thrombus. HCC was treated with local treatment of existing lesions (e.g., TACE, ablation, particle, TARE, hepatic arterial infusion chemotherapy, or radiotherapy). Patients who have previously received targeted or immunoreactive anti-tumor therapy for HCC and chemotherapy need to be desensitized for more than one month. Subjects were unable to perform enhanced CT or MRI scans of the liver. Have a history of liver transplantation or are currently candidates for liver transplantation. Patients at high risk for esophageal or gastric variceal bleeding or unproven severe variceal bleeding within the last 3 months. Have bleeding or thrombotic disease or are receiving thrombolytic therapy Study clinically significant hemoptysis or tumor hemorrhage of any cause within 2 weeks prior to initial administration of the intervention. Study of significant cardiovascular impairment in the 12 months prior to initial administration, such as a history of congestive heart failure above NYHA Grade II (Appendix 12), unstable angina, myocardial infarction or cerebrovascular stroke, or arrhythmias associated with hemodynamic instability. There was clinically significant ascites on physical examination, which could not be controlled by drugs. Known to be allergic to any component of icartin soft capsules and lenvatinib preparation. Pregnant or lactating female patients. Other conditions in which participation in the study is not appropriate according to the investigator's judgment.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    TACE +lenvatinib+Icaritin soft capsules

    Arm Description

    Trial drug Lenvatinib, 8mg (2 tablets for patients weighing less than 60kg), or 12mg (3 tablets for patients weighing more than 60kg), once daily. Icariin Soft Capsules 1200 mg/d (6 tablets in two doses) should be swallowed with warm water within 30 minutes after meal. Take lenvatinib and Icaritin soft capsules 3 to 5 days after TACE. Until the disease progresses or the patient becomes intolerant.

    Outcomes

    Primary Outcome Measures

    Objective Response Rate
    It was defined as the percentage of patients with complete response (CR) and partial response (PR) in all patients, and the treatment response was based on the modified response evaluation criteria in solid tumors (recist1.1)

    Secondary Outcome Measures

    progression-free survival
    It was defined as the time from successful hepatectomy to recurrence. Patients who withdraw or lose follow-up will be treated as deletion
    Overall Survival
    It was defined as the time from the beginning of treatment to death from any cause throughout the trial. Patients who dropped out or lost follow-up will be treated as deletion, and the known last survival date will be regarded as the last survival time. Patients who survived at the end of the study will also be treated as deletions, and the last known date of survival will be taken as the final survival time
    Disease Control Rate
    It was defined as the Proportion of all subjects receiving study therapy who rated complete response (CR), partial response (PR), and stable disease (SD) as best overall response according to RECIST 1.1 criteria.
    Duration of Response
    It was defined as the period from the date when tumor response was first recorded (as measured by RECIST 1.1 criteria) to the date when objective tumor progression was first recorded (as measured by RECIST 1.1 criteria) or the date of death from any cause.
    adverse event
    The incidence, severity, and serious adverse events associated with medication use were determined by NCI CTCAE v5.0 standards

    Full Information

    First Posted
    May 19, 2023
    Last Updated
    June 5, 2023
    Sponsor
    Zhejiang Cancer Hospital
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05903456
    Brief Title
    Icaritin Soft Capsule Combined With Lenvatinib and TACE for the Treatment of Hepatocellular Carcinoma
    Official Title
    Icaritin Soft Capsule Combined With Lenvatinib and Transcatheter Arterial Chemoembolization(TACE) for the Treatment of Hepatocellular Carcinomaunresectable, Non-metastatic Hepatocellular Carcinoma
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    June 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    July 2023 (Anticipated)
    Primary Completion Date
    May 2025 (Anticipated)
    Study Completion Date
    December 2025 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Zhejiang Cancer Hospital

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    The investigators design a phase II clinical study to explore the efficacy and safety of Transarterial Chemoembolization (TACE) + Lenvatinib + Icaritin soft capsules in patients with Unresectable, non-metastatic hepatocellular carcinoma and to analyze potential biomarkers of therapeutic response.
    Detailed Description
    This is a single-center, open-label, prospective, non-randomized clinical trial. We adopted the prospective cohort study to explore the safety and efficacy of Transarterial Chemoembolization (TACE) + Lenvatinib + Icaritin soft capsules in the patients with Unresectable, non-metastatic hepatocellular carcinoma. It is estimated that 20 patients who met the study criteria will be enrolled in Zhejiang Cancer Hospital. The investigators will follow up and collect subjects' data monthly to evaluate the efficacy and safety of treatment, including overall survival and time to progression. Multi-omics data analysis will be used to find potential biomarkers of treatment response.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Hepatocellular Carcinoma
    Keywords
    Hepatocellular carcinoma; Icaritin soft capsules;TACE; lenvatinib

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Masking Description
    NO masking
    Allocation
    N/A
    Enrollment
    20 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    TACE +lenvatinib+Icaritin soft capsules
    Arm Type
    Experimental
    Arm Description
    Trial drug Lenvatinib, 8mg (2 tablets for patients weighing less than 60kg), or 12mg (3 tablets for patients weighing more than 60kg), once daily. Icariin Soft Capsules 1200 mg/d (6 tablets in two doses) should be swallowed with warm water within 30 minutes after meal. Take lenvatinib and Icaritin soft capsules 3 to 5 days after TACE. Until the disease progresses or the patient becomes intolerant.
    Intervention Type
    Procedure
    Intervention Name(s)
    TACE(transcatheter arterial chemoembolization)
    Intervention Description
    TACE treatment is strictly in accordance with the Chinese guidelines for clinical practice of transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (2018 Edition). The patients with HCC were selected according to the inclusion criteria (referring to the conditions of the subjects). The subjects who met the inclusion criteria could enter the study after they signed the informed consent. 4-6 weeks after the first TACE treatment, the resectability criteria were evaluated. If not, the next cycle of TACE treatment was carried out. The general principle is to reduce the number of interventional treatment and extend the interval of interventional operation as far as possible under the condition of controlling the tumor and the survival of patients with tumor.
    Intervention Type
    Drug
    Intervention Name(s)
    lenvatinib
    Other Intervention Name(s)
    target drug
    Intervention Description
    Ronvastinib is an orally administered multi-receptor tyrosine kinase (RTK) inhibitor that selectively inhibits the kinase activity of vascular endothelial growth factor (VEGF) receptors, such as VEGF-1, VEGF-2, and VEGF-3, in addition to inhibiting other pro-angiogenic and oncogenic signaling pathways associated with tumor proliferation ,has been approved as a first-line treatment for liver cancer
    Intervention Type
    Drug
    Intervention Name(s)
    Icaritin soft capsules
    Other Intervention Name(s)
    Small molecule immunomodulator
    Intervention Description
    Icaritin soft capsule is a flavonoid compound extracted from traditional Chinese medicinal materials. It is a new type of small molecule immunomodulator. It is a 1.2 class of innovative Chinese medicine with global independent intellectual property rights. By inhibiting inflammatory signaling pathway and reducing the release of inflammatory factors, the immune microenvironment can be regulated to play an anti-tumor role. At present, it has been approved for first-line treatment of advanced liver cancer, with good efficacy and safety.
    Primary Outcome Measure Information:
    Title
    Objective Response Rate
    Description
    It was defined as the percentage of patients with complete response (CR) and partial response (PR) in all patients, and the treatment response was based on the modified response evaluation criteria in solid tumors (recist1.1)
    Time Frame
    48 weeks
    Secondary Outcome Measure Information:
    Title
    progression-free survival
    Description
    It was defined as the time from successful hepatectomy to recurrence. Patients who withdraw or lose follow-up will be treated as deletion
    Time Frame
    96 weeks
    Title
    Overall Survival
    Description
    It was defined as the time from the beginning of treatment to death from any cause throughout the trial. Patients who dropped out or lost follow-up will be treated as deletion, and the known last survival date will be regarded as the last survival time. Patients who survived at the end of the study will also be treated as deletions, and the last known date of survival will be taken as the final survival time
    Time Frame
    96 weeks
    Title
    Disease Control Rate
    Description
    It was defined as the Proportion of all subjects receiving study therapy who rated complete response (CR), partial response (PR), and stable disease (SD) as best overall response according to RECIST 1.1 criteria.
    Time Frame
    48 weeks
    Title
    Duration of Response
    Description
    It was defined as the period from the date when tumor response was first recorded (as measured by RECIST 1.1 criteria) to the date when objective tumor progression was first recorded (as measured by RECIST 1.1 criteria) or the date of death from any cause.
    Time Frame
    up to 48 weeks
    Title
    adverse event
    Description
    The incidence, severity, and serious adverse events associated with medication use were determined by NCI CTCAE v5.0 standards
    Time Frame
    96 weekes

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    80 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Between the ages of 18 and 80; Patients with histological/cytological confirmed hepatocellular carcinoma. HCC patients eligible for China liver cancer staging (CNLC) Stage IIIa, which cannot be resectable, are not suitable for radical treatment. According to the RECIST v1.1 standard, there must be at least one measurable lesion on the upper abdominal enhanced CT or MRI. Child-Pugh grade A or B; ECOG physical condition score is 0 or 1; Suitable for the indications of TACE surgery and chemotherapy drugs prescribed in advance by the research center, without any contraindications. Regular antiviral therapy should be given if HBV or HCV infection is present. Life expectancy is more than 3 months Able to swallow and absorb oral tablets; Appropriate organ function with the following laboratory test values obtained within 7 days prior to therapeutic use: (hemoglobin value ≥80g/L, neutrophil count ≥2.5×109/L, platelet count ≥75×109/L, serum total bilirubin ≤2× upper limit of normal (UNL), aspartic transferase ≤2×UNL, alanine transferase ≤3×UNL, serum creatinine ≤1.5×UNL) Manageable blood pressure Women of childbearing age must already be using reliable contraception or have had a negative pregnancy test (serum or urine) within 7 days prior to enrollment and be willing to use an effective method of contraception during the trial period and within 2 months after the last drug administration. Male subjects whose partners are women of childbearing age should use effective methods of contraception during the trial period and within 2 months after the last dose; The subjects voluntarily joined the study, signed the informed consent, had good compliance, and cooperated with follow-up. Exclusion Criteria: Formation of portal vein main cancer thrombus or extensive cancer thrombus. HCC was treated with local treatment of existing lesions (e.g., TACE, ablation, particle, TARE, hepatic arterial infusion chemotherapy, or radiotherapy). Patients who have previously received targeted or immunoreactive anti-tumor therapy for HCC and chemotherapy need to be desensitized for more than one month. Subjects were unable to perform enhanced CT or MRI scans of the liver. Have a history of liver transplantation or are currently candidates for liver transplantation. Patients at high risk for esophageal or gastric variceal bleeding or unproven severe variceal bleeding within the last 3 months. Have bleeding or thrombotic disease or are receiving thrombolytic therapy Study clinically significant hemoptysis or tumor hemorrhage of any cause within 2 weeks prior to initial administration of the intervention. Study of significant cardiovascular impairment in the 12 months prior to initial administration, such as a history of congestive heart failure above NYHA Grade II (Appendix 12), unstable angina, myocardial infarction or cerebrovascular stroke, or arrhythmias associated with hemodynamic instability. There was clinically significant ascites on physical examination, which could not be controlled by drugs. Known to be allergic to any component of icartin soft capsules and lenvatinib preparation. Pregnant or lactating female patients. Other conditions in which participation in the study is not appropriate according to the investigator's judgment.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    guoliang Shao, doctor
    Phone
    13958183472
    Email
    shaogl@zjcc.org.cn

    12. IPD Sharing Statement

    Plan to Share IPD
    No

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    Icaritin Soft Capsule Combined With Lenvatinib and TACE for the Treatment of Hepatocellular Carcinoma

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