Unresectable Hepatocellular Carcinoma (HCC)HLP1-1331NCT07596134
Multimodal Thermal Therapy With Targeted and Immunotherapy for Untreated Unresectable HCC
A study testing Multimodal Thermal Therapy and Targeted and Immune Drugs in people with Unresectable Hepatocellular Carcinoma (HCC), run by Zhejiang University at 7 sites in China.
Trial summary
Multimodal Thermal Therapy combined with targeted therapy and immunotherapy versus targeted therapy and immunotherapy alone for systemically untreated unresectable hepatocellular carcinoma (HCC) Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Unresectable Hepatocellular Carcinoma (HCC)
- What is being tested?
- Multimodal Thermal Therapy and Targeted and Immune Drugs
- Type of treatment
- Vaccines, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 166 participants
- Where
- 7 sitesChina
- Study dates
- 15 Oct 2026to 15 Oct 2029
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- • 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.
Who cannot join
- • Invasion of the main portal vein;
- Diffuse hepatocellular carcinoma;
- The hepatic lesion occupies more than 50% of the liver volume.
- 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;
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- 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.
Trial locations and contacts
7 sites in 1 country. Contact the study team or a site near you to ask about taking part.
7 sites in 1 country
China7 sites
First Division Hospital of Xinjiang Production and Construction Corps
Aksu, Xinjiang
Tao Ma, +86 13857148997, zjumatao@zju.edu.cn
Tao Ma, doctor's degree
The First Affiliated Hospital, Zhejiang University School of Medicine
Hangzhou, Zhejiang Provinece
Wang Xun, Doctor, +86 17857017882, 1322057@zju.edu.cn
Liang Tingbo, doctor's degree
The Second Affiliated Hospital, Zhejiang University School of Medicine
Hangzhou, Zhejiang Provinece
Tang Zhe, Doctor, +86 18867961022, 8xi@zju.edu.cn
Tang Zhe, doctor's degree
The First Hospital of Jiaxing
Jiaxing, Zhejiang Provinece
Xiaoguang Wang, +86 13967339225, wangxiaoguang@zjxu.edu.cn
Xiaoguang Wang, doctor's degree
Huaihe Hospital of Henan University
Kaifeng, Henan
Li Zexin, Doctor, +86 17701879927, lizexin403@126.com
Li Yan, doctor's degree
The Second Affiliated Hospital of Nanchang University
Nanchang, Jiangxi
Wang Kai, Doctor, +86 13767104812, neswk@163.com
Wang Kai, doctor's degree
Taizhou Hospital of Zhejiang Province
Taizhou, Zhejiang Provinece
Fabiao Zhang, +86 13706760105, zhangfabiao@enzemed.com
Fabiao Zhang, doctor's degree
About this study
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.
Multimodal Thermal Therapy combined with targeted therapy and immunotherapy versus targeted therapy and immunotherapy alone for systemically untreated unresectable hepatocellular carcinoma (HCC)
Read the 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), 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.
- Being tested
- Multimodal Thermal Therapy, Targeted and Immune Drugs
- Keywords
- HCC
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Multimodal Thermal TherapyDevice
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.
Targeted and Immune DrugsDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Experimental group | Experimental | Multimodal Thermal Therapy Combined with Targeted and Immune Drugs Receives: Device: Multimodal Thermal Therapy; Drug: Targeted and Immune Drugs |
| Control Group | Active comparator | Targeted and Immune Drugs Receives: Drug: Targeted and Immune Drugs |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to ~24 months.
Secondary outcomes (8)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Up to ~36 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 May 2026
- Study start15 Oct 2026 (estimated)
- Primary completion15 Oct 2028 (estimated)
- Study completion15 Oct 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Unresectable Hepatocellular Carcinoma (HCC)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 166 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Zhejiang University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, TingBo Liang, Zhejiang University
- Investigators
- Liang Tingbo, doctor's degree, Principal investigator, First Affiliated Hospital of Zhejiang University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07596134
- Sponsor's protocol ID
- HLP1-1331
- Acronym
- HLP1-1331
- Status last verified
- Sep 2026
- First submitted
- 2 May 2026
- Last updated
- 22 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT07596134
- Acronym / sponsor ID
- HLP1-1331 / HLP1-1331
- Keywords
- HCC
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 166 participants (estimated)
- Lead sponsor
- Zhejiang UniversityUniversity, hospital or other
- Study start
- 15 Oct 2026 (estimated)
- Primary completion
- 15 Oct 2028 (estimated)
- Study completion
- 15 Oct 2029 (estimated)
- First posted
- 19 May 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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), 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Experimental group | Experimental | Device: Multimodal Thermal Therapy, Drug: Targeted and Immune DrugsMultimodal Thermal Therapy Combined with Targeted and Immune Drugs |
| Control Group | Active comparator | Drug: Targeted and Immune DrugsTargeted and Immune Drugs |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- • Age 18-80, regardless of gender;
Key exclusion criteria (17 listed)
- • Invasion of the main portal vein;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Multimodal Thermal TherapyMultimodal 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. | Device | Experimental group |
| Targeted and Immune DrugsIn 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. | Drug | Control Group, Experimental group |
Primary outcome
Progression-free survival (PFS) per mRECIST
Time frame: 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.
8 secondary outcomes
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.
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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Sep 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Liang Tingbo, doctor's degree principal investigator
First Affiliated Hospital of Zhejiang University
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Multimodal Thermal Therapy and Targeted and Immune Drugs in people with Unresectable Hepatocellular Carcinoma (HCC), run by Zhejiang University at 7 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 22 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Wang Xun, Doctor (+86 17857017882, 1322057@zju.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free survival (PFS) per mRECIST (time frame: Up to ~24 months.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Sep 2026.