Clinical trial NCT06285149: Tace With Icaritin in First-line Treatment of Middle and Advanced HCC in Child Grade B Patients
Official title: Prospective Single-arm, Single-center Exploratory Clinical Study on Efficacy and Safety of Interventional Therapy Combined With Icaritin in First-line Treatment of Middle and Advanced HCC in Child Grade B Patients
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: HCC
Lead sponsor: Henan Cancer Hospital
Sponsor class: OTHER_GOV
First posted: 2024-02-29
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Icaritin is a drug that has been approved by the National Medical Products Administration (NMPA) based on a multicenter, randomized, double-blind, parallel-controlled Phase III clinical trial - SNG1705 ICR-1. It is used for patients with unresectable hepatocellular carcinoma who are not suitable for or refuse standard treatment and have not previously received systemic therapy. According to numerous studies, in tumor cells, Icaritin can downregulate the expression of TNF-α, IL-6, PD-L1 and exert anti-tumor effects. At the same time, it regulates the tumor immune microenvironment by reducing the secretion of TNFa and IL-6 as well as inhibiting PD-L1 expression through decreasing MDSC cell proportion. Importantly, Icaritin has excellent safety profile and greatly ensure patients' quality of life clinically. Rare grade 3-4 TRAEs were observed in clinical trials which is uncommon among existing standard drugs. Good safety is a prerequisite for combination therapy; therefore, further exploration of optimal drug combinations is worth considering. Thus, TACE+Icaritin may potentially optimize treatment strategies for patients with poor liver function reserve.

Detailed description: Child B patients have a lower tolerance to targeted immunotherapy, and combining interventional therapy with targeted immunotherapy can result in an accumulation of toxic side effects leading to disease progression. Additionally, repeated local interventions can further deteriorate liver function. These patients currently face limited treatment choices. Apatinib has minimal adverse reactions and has been recommended by experts as a level I option for Child B patients in the HCC 2022 CSCO guidelines. Therefore, combining interventional therapy with apatinib holds promise in improving survival outcomes for Child B patients.

Eligibility criteria: Inclusion Criteria:

1. HCC was confirmed by histopathology or clinical diagnosis;
2. No previous systematic therapy;
3. Age 18-75 years old;
4. CNLC: Ⅱb-Ⅲa stage;
5. Child-Pugh grade B;
6. ECOG PS score :0-1;
7. No major vessel invasion or distant metastasis;
8. Suitable for interventional treatment;
9. Measurable disease according to mRECIST;
10. Willing to sign informed consent;
11. Willing and able to follow study protocols and visit plans.

Exclusion Criteria:

1. Patients who refuse or are not suitable for interventional treatment;
2. Fibrolamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, cholangiocarcinoma and other components previously confirmed by histology/cytology;
3. Prior systematic therapy for HCC, including chemotherapy agents, sorafenib, Renvastinib, regorafenib and other targeted agents or immunomodulators such as anti-PD-1, anti-PD-L1, anti-CTLA-4, other than antiviral therapy for patients receiving any other investigational drug;
4. Contraindications for interventional therapy, such as severe cirrhosis, more than moderate ascites, and Child C liver function; 5, diagnosed as hepatic encephalopathy, sclerosing cholangitis, Gilbert disease;

6. A history of gastrointestinal bleeding or a definite tendency to gastrointestinal bleeding within the previous 6 months; 7. Serious dysfunction of vital organs such as heart, brain and lungs; 8.uncontrolled high blood pressure, gastrointestinal bleeding or coagulation dysfunction, etc.; 9. Pregnant or nursing patients; 10. Allergic to drugs or excipients used in the study; 11. Other conditions deemed inappropriate for participation in the study by the investigator.

Primary outcomes:
measure: ORR
timeFrame: 2 years
measure: PFS
timeFrame: 2 years
Secondary outcomes:
measure: Overall survival，OS
timeFrame: 2 years
Other outcomes:
Locations:
Study officials:
References: