Unresectable Hepatocellular Carcinoma (HCC)
Conditions
Keywords
HCC
Brief summary
Multimodal Thermal Therapy combined with targeted therapy and immunotherapy versus targeted therapy and immunotherapy alone for systemically untreated unresectable hepatocellular carcinoma (HCC)
Detailed description
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), pain levels via VAS scores, 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.
Interventions
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.
DRUGTargeted and Immune Drugs
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.
Sponsors
Zhejiang University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* • Age 18-80, regardless of gender; * Diagnosed with unresectable HCC by imaging or histology, BCLC stage B or C; * No prior systemic immunotherapy, chemotherapy, targeted therapy, or other systemic drug treatments for HCC; * Presence of an image-evaluable lesion intended for ablation without prior local ablation therapy, with the maximum diameter of the target tumor ≤5 cm; * Child-Pugh score ≤7; * ECOG-PS score of 0-1.
Exclusion criteria
* • Invasion of the main portal vein; * Diffuse hepatocellular carcinoma; * Patients with a history or current diagnosis of brain metastases whose symptoms are not fully controlled (i.e., persistent or worsening symptoms, or requiring adjustments to symptomatic treatment to maintain symptom relief); * Extensive distant metastasis confirmed by imaging (e.g., chest/abdominal CT/MRI, whole-body bone scan, PET-CT, etc.), including but not limited to diffuse lung metastasis, multiple bone metastases, extensive abdominal/peritoneal metastasis, or other multi-organ metastases, where the investigator assesses that the extent of metastasis may compromise the safe administration of study treatment or affect efficacy and safety evaluations; * Prior local therapy with the last treatment administered less than 4 weeks before enrollment; * Involvement of major blood vessels such as the hepatic vein or inferior vena cava; * Uncontrolled active infection; * Renal dysfunction with serum creatinine \>176.8 μmol/L or creatinine clearance \<30 mL/min; * Uncorrectable coagulation abnormalities: platelets \<50×10⁹/L, prothrombin time \>18 seconds, prothrombin activity \<40%, and uncorrectable; * History of esophageal or gastric variceal bleeding without effective treatment via endoscopy, intervention, or surgery; * Patients with active psychiatric disorders; * Patients receiving or requiring systemic glucocorticoids (e.g., prednisone, dexamethasone) at a dose ≥10 mg/day (prednisone equivalent) or other immunosuppressive drugs (e.g., cyclosporine, tacrolimus, methotrexate) within 14 days prior to enrollment; topical, inhaled, or ophthalmic glucocorticoid use that does not affect systemic immune function may be allowed at the investigator's discretion; * History or current diagnosis of malignancies other than the target tumor in this study (excluding cured low-grade malignancies such as basal cell carcinoma, squamous cell carcinoma of the skin, or cervical carcinoma in situ). For low-grade malignancies, eligibility will be determined by the investigator; * Pregnant or breastfeeding women, or women of childbearing potential planning pregnancy during the study or within 3 months after treatment completion; * Expected survival \<3 months; * Patients deemed unsuitable for participation by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival (PFS) per mRECIST | Up to ~24 months. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) per mRECIST | Up to ~24 months. | 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. |
| Objective Response Rate (ORR) per RECIST 1.1 | Up to ~24 months. | 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. |
| Progression-free survival (PFS) per RECIST 1.1 | Up to ~24 months. | 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. |
| Overall Survival | Up to ~36 months. | Overall survival (OS) was defined as the time from randomization to all-cause death, with outcome assessments conducted by on-site investigators. |
| Disease Control Rate (DCR) per RECIST 1.1 | Up to ~24 months. | 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. |
| Disease Control Rate (DCR) per mRECIST | Up to ~24 months. | 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. |
| Visual Analogue Scale | During the MTT procedure only. | The VAS score ranges from 0 to 10, with 0 indicating no pain at all and 10 representing the worst possible pain. |
| Percentage of Participants Who Experience At Least One Adverse Event (AE) | Up to ~36 months. | 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. |
| Percentage of Participants Who Experience At Least One Serious Adverse Event (SAE) | Up to ~36 months. | 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. |
Countries
China
Contacts
CONTACTWang Xun, Doctor
PRINCIPAL_INVESTIGATORLiang Tingbo, doctor's degree
Zhejiang University
Outcome results
None listed