An interventional study of Multimodal Thermal Therapy and Targeted and Immune Drugs in Unresectable Hepatocellular Carcinoma (HCC), sponsored by Zhejiang University. Not yet recruiting at 7 sites in China. Open to participants aged 18 Years to 80 Years. Per ClinicalTrials.gov, last updated 2026-09-22.
Sponsored by Zhejiang University · Not applicable, Interventional, and Treatment
Multimodal Thermal Therapy combined with targeted therapy and immunotherapy versus targeted therapy and immunotherapy alone for systemically untreated unresectable hepatocellular carcinoma (HCC)
This prospective, multicenter, open-label, randomized controlled study is titled "Multimodal Thermal Therapy combined with targeted therapy and immunotherapy versus targeted therapy and immunotherapy alone for systemically untreated unresectable hepatocellular carcinoma (HCC)". The research aims to evaluate the clinical benefits of combining local intervention with systemic treatments. The primary objective is to compare the progression-free survival (PFS) between the combination therapy and standard systemic therapy. Secondary objectives include assessing the objective response rate (ORR), disease control rate (DCR), overall survival (OS), and general safety. Furthermore, the study includes an exploratory goal of monitoring changes in peripheral blood immune indicators to analyze the impact of the combined treatment on the patient's immune function. The study aims to enroll a total of 166 patients, who are randomized in a 1:1 ratio into either an experimental group or a control group, resulting in 83 participants per arm. Eligible participants are adults aged 18 to 80 with unresectable HCC staged as BCLC B or C who have not previously received systemic drug therapy. Inclusion requires a Child-Pugh score of 7 or less, an ECOG-PS score of 0 to 1, and at least one evaluable lesion suitable for ablation with a maximum diameter of 5 cm. Patients are excluded if they have portal vein main trunk invasion, diffuse HCC, symptomatic brain metastases, or extensive distant metastases.
Age 18-80, regardless of gender;
Exclusion Criteria:
Invasion of the main portal vein;
Multimodal Thermal Therapy Combined with Targeted and Immune Drugs
Device: Multimodal Thermal Therapy · Drug: Targeted and Immune Drugs
Targeted and Immune Drugs
Drug: Targeted and Immune Drugs
Multimodal Thermal Therapy (MTT) is an advanced ablation technique that utilizes an integrated microprobe to combine liquid nitrogen freezing with radiofrequency heating. This dual-action process creates a rapidly shifting temperature field and significant tissue stress, leading to the complete destruction of tumor cells and their associated blood vessels. Beyond local tumor removal, the procedure acts as an "in situ vaccine" by releasing tumor-associated antigens and danger signals into the bloodstream, which activates a systemic and durable anti-tumor immune response.
In this research, systemic treatment specifically refers to the combination of targeted therapies and immune checkpoint inhibitors, such as PD-1 inhibitors. These drugs are selected based on their approval by the NMPA for liver cancer treatment and the specific clinical needs of the patient. The primary role of the immune drugs is to block immune checkpoints, which prevents the tumor from escaping the body's defenses and significantly enhances the natural anti-tumor function of T cells. Complementing this, the targeted drugs-often anti-angiogenic agents-work to inhibit tumor blood vessel growth and improve the overall immune microenvironment. When used together, they create a synergistic "dual" effect: the targeted drugs optimize the environment for immune cell infiltration while the immune drugs activate T cells to more effectively attack the cancer.
Progression-free survival (PFS) per mRECIST
Progression-free survival (PFS) was defined as the interval from randomization to initial confirmed disease progression or all-cause death, whichever came first, with tumor assessments conducted per mRECIST by on-site investigators.
Time frame: Up to ~24 months.
Objective Response Rate (ORR) per mRECIST
ORR is defined as the percentage of participants who have a confirmed complete response (CR: disappearance of any intratumoral arterial enhancement in all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters of viable \[enhancement in the arterial phase\] target lesions, taking as reference the baseline sum of the diameters of target lesions), with tumor assessments conducted per mRECIST by on-site investigators.
Time frame: Up to ~24 months.
Objective Response Rate (ORR) per RECIST 1.1
Objective response rate (ORR) was defined as the proportion of participants achieving confirmed complete response or partial response, with tumor assessments conducted per RECIST 1.1 by on-site investigators.
Time frame: Up to ~24 months.
Progression-free survival (PFS) per RECIST 1.1
Progression-free survival (PFS) was defined as the interval from randomization to initial confirmed disease progression or all-cause death, whichever came first, with tumor assessments conducted per RECIST 1.1 by on-site investigators.
Time frame: Up to ~24 months.
Overall Survival
Overall survival (OS) was defined as the time from randomization to all-cause death, with outcome assessments conducted by on-site investigators.
Time frame: Up to ~36 months.
Disease Control Rate (DCR) per RECIST 1.1
Disease control rate (DCR) was defined as the proportion of participants achieving confirmed complete response, partial response or stable disease, with tumor assessments conducted per RECIST 1.1 by on-site investigators.
Time frame: Up to ~24 months.
Disease Control Rate (DCR) per mRECIST
Disease control rate (DCR) was defined as the proportion of participants achieving confirmed complete response, partial response or stable disease, with tumor assessments conducted per mRECIST by on-site investigators.
Time frame: Up to ~24 months.
Percentage of Participants Who Experience At Least One Adverse Event (AE)
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experience at least one AE will be reported.
Time frame: Up to ~36 months.
Percentage of Participants Who Experience At Least One Serious Adverse Event (SAE)
An SAE is an AE that results in death, is life threatening, requires or prolongs a hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, is a cancer, is associated with an overdose, or is another important medical event. The percentage of participants who experience at least one SAE will be reported.
Time frame: Up to ~36 months.
Plan to share: No
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Zhejiang University