Multimodal Thermal Therapy Combined With Targeted Therapy and Immunotherapy Versus Targeted Therapy and Immunotherapy Alone for Systemically Untreated Unresectable Hepatocellular Carcinoma (HCC).

NCT07596134 | Not Yet Recruiting

• 1 other identifier: HLP1-1331
• Study Type: interventional
• Target: 166
• Locations: 1 country
• Sites: 4

Brief Summary

Multimodal Thermal Therapy combined with targeted therapy and immunotherapy versus targeted therapy and immunotherapy alone for systemically untreated unresectable hepatocellular carcinoma (HCC)

Conditions

Unresectable Hepatocellular Carcinoma (HCC)

Keywords

HCC

Outcome Measures

Primary Outcomes (1)

• Progression-free survival

  From the completion of randomization to the time of disease progression (imaging) or death

  At 1 month, 3 months, and every 3 months thereafter until disease progression or death, assessed up to 24 months.

Secondary Outcomes (6)

• Objective Response Rate

  At 1 month, 3 months, and every 3 months thereafter until disease progression or study completion, assessed up to 24 months.

• Overall Survival

  From the date of randomization until the date of death from any cause, assessed up to 36 months.

• Disease Control Rate

  At 1 month, 3 months, and every 3 months thereafter until disease progression or death, assessed up to 24 months.

• Visual Analogue Scale

  VAS assessment is performed only during the MTT procedure.

• Adverse events

  From the date of informed consent through 30 days after the last treatment, assessed up to 24 months.

Study Arms (2)

Experimental group

EXPERIMENTAL

Multimodal Thermal Therapy Combined with Targeted and Immune Drugs

Device: Multimodal Thermal Therapy; Drug: Targeted and Immune Drugs

Control Group

ACTIVE COMPARATOR

Targeted and Immune Drugs

Drug: Targeted and Immune Drugs

Interventions

Multimodal Thermal Therapy DEVICE

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.

Experimental group

Targeted and Immune Drugs DRUG

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.

Control Group; Experimental group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• Zhejiang University: lead

Study Sites (4)

Huaihe Hospital of Henan University

Kaifeng, Henan, China

Location

The Second Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, China

Location

The First Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang Provinece, China

Location

The Fourth Affiliated Hospital, Zhejiang University School of Medicine

Yiwu, Zhejiang Provinece, China

Location

Study Officials

• Liang Tingbo, doctor's degree

  Zhejiang University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Wang Xun, Doctor

CONTACT

+86 17857017882; 1322057@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director physician

Study Record Dates

• First Submitted: May 2, 2026
• First Posted: May 19, 2026
• Study Start (Estimated): May 25, 2026
• Primary Completion (Estimated): May 25, 2028
• Study Completion (Estimated): May 25, 2029
• Last Updated: May 19, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (4)