Clinical trial NCT06363006: Combination of Cardonizumab Injection and TKI Second Line Therapy for Advanced Hepatocellular Cancer
Official title: Evaluation of the Efficacy and Safety of Cardonilimab Injection Combined With TKI as Second-line Treatment for Advanced Hepatocellular Carcinoma: A Single-arm, Open-label, Multicenter Real-world Clinical Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Hepatocellular Carcinoma
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
First posted: 2024-04-12
Enrollment: 40
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: The goal of this clinical trial is to evaluate the efficacy and safety of cardonilizumab injection combined with TKI in second-line treatment of advanced hepatocellular carcinoma. The main questions it aims to answer are:

* Objective response rate (ORR) for evaluation
* Disease Control Rate (DCR); Duration of relief (DoR); Progression free survival (PFS); Total survival time (OS); Safety。

Detailed description: Have received at least one prior systemic treatment progression or intolerance for HCC. Cardonilizumab was administered every 2 weeks on the first day of each cycle for up to 24 months in the absence of investigator judgment that there is no longer a clinical continuation benefit, intolerable toxicity, initiation of a new antitumor therapy, withdrawal of informed consent, loss of follow-up, death, or other protocol requirements for treatment termination. Cardonilizumab will complete infusion within 60 minutes (± 10 minutes). Continuous monitoring of potential infusion reactions and allowing pre-treatment of hypersensitivity reactions or infusion rate adjustment according to protocol guidelines. For subjects who cannot tolerate a 60-minute infusion, the infusion time can be extended up to 120 minutes. Dose adjustment of cardonilizumab is not allowed during treatment, but delayed dosing is allowed for up to 12 weeks (since the last dosing time). If glucocorticoids are used in the treatment of irAE, In both cases where the glucocorticoid reduction process resulted in the suspension of cardonilizumab for more than 12 weeks, or in the treatment of AE that may or may not be related to cardonilizumab, and where the investigator determined that the patient would benefit from continued treatment, permission to continue treatment was required after discussion with the sponsor medical Ombudsman.

Eligibility criteria: Inclusion Criteria:Participants must meet all of the following inclusion criteria to be admitted to the study:

1. Patients with histologically/cytologically confirmed hepatocellular carcinoma or cirrhosis meet the clinical diagnostic criteria of the American Association for the Study of Liver Diseases (AASLD) for hepatocellular carcinoma.
2. Age ≥18 and ≤75 years old.
3. ECOG physical status score 0 or 1.
4. Barcelona Clinic Liver Cancer (BCLC) stage C; It is not suitable for radical surgery and/or local treatment or stage B that progresses irremediably after surgery and/or local treatment.
5. Progression or intolerance after receiving at least one systemic antitumor therapy for hepatocellular carcinoma prior to initial administration
6. According to RECIST v1.1, there is at least one untreated measurable lesion or one that has been locally treated (e.g., Measurable lesions with clear progression (RECIST v1.1 standard) after radiofrequency ablation, injection of anhydrous ethanol or acetic acid, cryoablation, high-intensity focused ultrasound, transarterial embolization chemotherapy, transarterial embolization, etc., can be measured repeatedly.
7. Child-Pugh Level A.
8. Any treatment-related toxicity (due to prior treatment) must be resolved to baseline or stable prior to enrollment, except for hair loss.

Exclusion Criteria:Participants who meet any of the following criteria will not be eligible to participate in the study:

1. Fibrolamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma and other components previously confirmed by histology/cytology.
2. History of hepatic encephalopathy.
3. History of liver transplantation.
4. There is clinically significant pericardial effusion; There are clinical symptoms of a pleural effusion requiring drainage.
5. Clinically significant ascites are defined as meeting the following criteria: ascites can be detected by physical examination during screening or ascites need to be drained during screening.
6. Co-infection with HBV and HCV (a history of HCV infection but negative HCV RNA can be considered not infected with HCV).
7. There is central nervous system metastasis or meningeal metastasis.
8. Bleeding from esophageal or fundus varices caused by portal hypertension occurred within 6 months before the first dose Event. A gastroscopy must have been performed within 6 months prior to initial dosing, and participants with severe (G3) varicose veins were not allowed to participate in the study.
9. Patients with any physical signs or history of bleeding, regardless of severity; Patients with any bleeding or bleeding event ≥CTCAE grade 3 within 4 weeks prior to initial dosing

Primary outcomes:
measure: ORR Full single-arm, open, multicenter prospective clinical study
timeFrame: 3 years
measure: Progression-free Survival (PFS)
timeFrame: 1.5 years
Secondary outcomes:
measure: Disease Control Rate (DCR)
timeFrame: 3 years
measure: Overall Survival (OS)
timeFrame: 3 years
measure: Duration of Response (DOR)
timeFrame: 3 years
measure: Stable Disease (SD)
timeFrame: 3 years
measure: Progression free survival rate
timeFrame: 1.5 years
Other outcomes:
measure: Any adverse events related with treatment with TKI plus Cardonizumab.
timeFrame: 3 years
Locations:
city: Beijing
country: China
facility: Chinese Academy of Medical Sciences & Peking Union Medical College Hospital (CAMS&PUMCH)
state: Beijing
Study officials:
References: