Multimodal Thermal Therapy With Targeted and Immunotherapy for Untreated Unresectable HCC

Official title

Multimodal Thermal Therapy With Targeted Therapy and Immunotherapy Versus Targeted Therapy and Immunotherapy Alone for Systemically Untreated Unresectable (HCC): a Prospective, Multicenter, Open-label, Randomized Controlled Trial.

Overview

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

• Device Multimodal Thermal Therapy
  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 blo
• Drug Targeted 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. Compleme

Primary outcome measures

• Progression-free survival (PFS) per mRECIST [Time frame: Up to ~24 months.]

Secondary outcome measures (9)

• Objective Response Rate (ORR) per mRECIST [Time frame: Up to ~24 months.]
• Objective Response Rate (ORR) per RECIST 1.1 [Time frame: Up to ~24 months.]
• Progression-free survival (PFS) per RECIST 1.1 [Time frame: Up to ~24 months.]
• Overall Survival [Time frame: Up to ~36 months.]
• Disease Control Rate (DCR) per RECIST 1.1 [Time frame: Up to ~24 months.]
• Disease Control Rate (DCR) per mRECIST [Time frame: Up to ~24 months.]
• Visual Analogue Scale [Time frame: During the MTT procedure only.]
• Percentage of Participants Who Experience At Least One Adverse Event (AE) [Time frame: Up to ~36 months.]
• Percentage of Participants Who Experience At Least One Serious Adverse Event (SAE) [Time frame: Up to ~36 months.]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 4 centers

• Huaihe Hospital of Henan University — Kaifeng
• The Second Affiliated Hospital of Nanchang University — Nanchang
• The First Affiliated Hospital, Zhejiang University School of Medicine — Hangzhou
• The Fourth Affiliated Hospital, Zhejiang University School of Medicine — Yiwu

Identifiers

NCT: NCT07596134 · HLP1-1331

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗