Hepatocellular CarcinomaNCT06265350
Cryoablation Combined With Cardonilizumab and Bevacizumab in Hepatocellular Carcinoma With Pulmonary Metastases
A study testing Cadonilimab, Bevacizumab and Cryoablation in people with Hepatocellular Carcinoma and Liver Cancer Stage IV, run by Sun Yat-sen University at 2 sites in China.
Trial summary
This study intends to evaluate the efficacy and safety of cryoablation combined with Cardonilizumab and Bevacizumab in hepatocellular carcinoma with pulmonary metastases. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Hepatocellular Carcinoma, Liver Cancer Stage IV, Pulmonary Metastases
- What is being tested?
- Cadonilimab, Bevacizumab and Cryoablation
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 2 sitesChina
- Study dates
- 2 Feb 2024to 30 Jan 2027
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- primary or recurrent HCC;
- synchronous metastases (within one month after diagnosing of HCC) or asynchronous metastases (more than one month after diagnosis of HCC);
- pulmonary-only metastases >5 and ≤10;
- metastases diameter ≤ 5 cm;
- intrahepatic tumors ≤5, and tumor burden ≤1/2 liver volume;
- PVTT type Vp≤3;
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- patients underwent first-line system therapy failure, the first-line system included tyrosine kinase inhibitor (TKI), such as Sorafenib or Lenvatinib, with or without PD-1 or PDL1 inhibitor;
- the intrahepatic tumors were effectively controlled and pulmonary metastases were no progression, and the controlled intrahepatic tumors were defined as partial or stable response according to modified Response Evaluation Criteria in Solid Tumors (mRECIST);
- locoregional therapy (including TACE or HAIC) were also included;
- Child-Pugh class A or B;
- PS 0 or 1;
- no history of other malignancies.
Who cannot join
- under 18 years or over 75 years;
- metastases >10
- non-lung metastases;
- incomplete clinical data;
- metastases diameter > 5 cm;
- intrahepatic tumors > 5, and tumor burden > 1/2 liver volume;
- PVTT type Vp 4;
- lost to follow-up within 3 months.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
China2 sites, 2 recruiting
- Recruiting
Sun Yat-sen University Cancer Center
Guanzhou, Guangdong, 510000
Qunfang Zhou, MD, 86 19868000115, zhouqun988509@163.com
- Recruiting
Sun Yat-sen University Cancer Center
Guanzhou, Guangdong, 510000
Qunfang Zhou, MD, 8619868000115, zhouqun988509@163.com
About this study
Official title: Cryoablation Combined With Cardonilizumab and Bevacizumab in Hepatocellular Carcinoma With Pulmonary Metastases: A Single-center, Prospective, Randomized Controlled Phase II Study
This study intends to evaluate the efficacy and safety of cryoablation combined with Cardonilizumab and Bevacizumab in hepatocellular carcinoma with pulmonary metastases.
Read the detailed description
For advanced hepatocellular carcinoma (HCC), the lung is the most common metastatic organ, accounting for 30-50% of extrahepatic diseases. The standard therapy for advanced HCC with lung metastases according to the Barcelona Clinic Liver Cancer (BCLC) criteria is system therapy.
However, studies have proven that palliative ablation could improve the tumor controlling effect and the outcomes.
Cryoablation is a treatment method that involves freezing tumors at extremely low temperatures to destroy and eliminate them. This therapeutic approach can result in the death of tumor cells through necrosis and also stimulate immune targeting of tumor cells. These immune responses occur as a result of tumor cell death caused by the ablation procedure. In comparison to conventional cancer therapies, cryoablation has minimal adverse reactions and has the potential to promote a more extensive and effective release of self-generated antigens into the bloodstream.
Targeting vascular endothelial growth factor (VEGF) could reduce VEGF-mediated immunosuppression within the tumor. The IMbrave150 study of atezolizumab and bevacizumab versus sorafenib demonstrated response rates of 29.8% vs 12%, respectively, and median overall survival of 19.8 months in the combination arm versus 13.4 months in the sorafenib (P <0.001). Bevacizumab could enhance anti-PD-1 and anti-programmed death ligand 1 (PD-L1) efficacy by reversing VEGF-mediated immunosuppression and promoting T-cell infiltration in tumors (2).
Cadonilimab is a first-in-class bispecific, humanized IgG1 antibody targeting PD-1 and CTLA-4, which has the potential to boost immune surveillance in tumors. Preclinical studies have shown that its tetravalent design enhances its high binding activity in the tumor microenvironment. With no Fc binding, Cadonilimab could eliminate a series of functions mediated by the Fc receptor, which contribute to a poor safety profile in clinical settings.
- Conditions
- Hepatocellular Carcinoma, Liver Cancer Stage IV, Pulmonary Metastases, Cadonilimab, Bevacizumab, Cryoablation
- Being tested
- Cadonilimab, Bevacizumab, Cryoablation
- Medical subject headings
- Carcinoma, Hepatocellular, Liver Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CadonilimabDrug
Cadonilimab, 375mg，Q3W， IV
BevacizumabDrug
Bevacizumab, 7.5mg/kg，Q3W， IV
CryoablationProcedure or surgery
Patients accepted Cryoablation of pulmanary metastases
| Study group | Role | What they receive |
|---|---|---|
| Bevacizumab+Cadonilimab group | Active comparator | Patients accepted Bevacizumab (7.5mg/kg，Q3W， IV) plus Cadonilimab (375mg，Q3W， IV) Receives: Drug: Cadonilimab; Drug: Bevacizumab |
| Cryoablation+Bevacizumab+Cadonilimab | Experimental | Patients accepted Cryoablation of pulmanary metastases combined with Bevacizumab (7.5mg/kg，Q3W， IV) and Cadonilimab (375mg，Q3W， IV) Receives: Drug: Cadonilimab; Drug: Bevacizumab; Procedure: Cryoablation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective response rate (ORR)
ORR, as determined based on tumor response according to RECIST 1.1, is defined as partial response and complete response.
Measured: 6 months
Secondary outcomes (2)
Progression free survival (PFS)
PFS is defined as the time from the date of inclusion to the date of the first objectively documented tumor progression or death due to any cause.
Measured: 6 months
Overall survival (OS)
OS is the length of time from the date of inclusion until death from any cause.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Feb 2024
- Study start2 Feb 2024
- Primary completion30 Jan 2026 (estimated)
- Study completion30 Jan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- More trials run by Sun Yat-sen UniversityThe sponsor's other registered studies.
- 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
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sun Yat-sen University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Zhou Qunfang, Sun Yat-sen University
- Investigators
- Zhimei Hunag, MD, Study director, Sun Yat-sen UniversityJinhua Huang, MD, Study director, Sun Yat-sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06265350
- Sponsor's protocol ID
- Liver Project 5
- Status last verified
- Feb 2024
- First submitted
- 2 Feb 2024
- Last updated
- 20 Feb 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cryoablation Combined With Cardonilizumab and Bevacizumab in Hepatocellular Carcinoma With Pulmonary Metastases: A Single-center, Prospective, Randomized Controlled Phase II Study
- ClinicalTrials.gov ID
- NCT06265350
- Acronym / sponsor ID
- Liver Project 5
- Conditions
- Hepatocellular Carcinoma, Liver Cancer Stage IV, Pulmonary Metastases, Cadonilimab, Bevacizumab, Cryoablation
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Sun Yat-sen UniversityUniversity, hospital or other
- Study start
- 2 Feb 2024 (actual)
- Primary completion
- 30 Jan 2026 (estimated)
- Study completion
- 30 Jan 2027 (estimated)
- First posted
- 20 Feb 2024 (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.
This study intends to evaluate the efficacy and safety of cryoablation combined with Cardonilizumab and Bevacizumab in hepatocellular carcinoma with pulmonary metastases.
Detailed description
For advanced hepatocellular carcinoma (HCC), the lung is the most common metastatic organ, accounting for 30-50% of extrahepatic diseases. The standard therapy for advanced HCC with lung metastases according to the Barcelona Clinic Liver Cancer (BCLC) criteria is system therapy.
However, studies have proven that palliative ablation could improve the tumor controlling effect and the outcomes.
Cryoablation is a treatment method that involves freezing tumors at extremely low temperatures to destroy and eliminate them. This therapeutic approach can result in the death of tumor cells through necrosis and also stimulate immune targeting of tumor cells. These immune responses occur as a result of tumor cell death caused by the ablation procedure. In comparison to conventional cancer therapies, cryoablation has minimal adverse reactions and has the potential to promote a more extensive and effective release of self-generated antigens into the bloodstream.
Targeting vascular endothelial growth factor (VEGF) could reduce VEGF-mediated immunosuppression within the tumor. The IMbrave150 study of atezolizumab and bevacizumab versus sorafenib demonstrated response rates of 29.8% vs 12%, respectively, and median overall survival of 19.8 months in the combination arm versus 13.4 months in the sorafenib (P <0.001). Bevacizumab could enhance anti-PD-1 and anti-programmed death ligand 1 (PD-L1) efficacy by reversing VEGF-mediated immunosuppression and promoting T-cell infiltration in tumors (2).
Cadonilimab is a first-in-class bispecific, humanized IgG1 antibody targeting PD-1 and CTLA-4, which has the potential to boost immune surveillance in tumors. Preclinical studies have shown that its tetravalent design enhances its high binding activity in the tumor microenvironment. With no Fc binding, Cadonilimab could eliminate a series of functions mediated by the Fc receptor, which contribute to a poor safety profile in clinical settings.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Bevacizumab+Cadonilimab group | Active comparator | Drug: Cadonilimab, Drug: BevacizumabPatients accepted Bevacizumab (7.5mg/kg，Q3W， IV) plus Cadonilimab (375mg，Q3W， IV) |
| Cryoablation+Bevacizumab+Cadonilimab | Experimental | Drug: Cadonilimab, Drug: Bevacizumab, Procedure: CryoablationPatients accepted Cryoablation of pulmanary metastases combined with Bevacizumab (7.5mg/kg，Q3W， IV) and Cadonilimab (375mg，Q3W， IV) |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- primary or recurrent HCC;
- synchronous metastases (within one month after diagnosing of HCC) or asynchronous metastases (more than one month after diagnosis of HCC);
- pulmonary-only metastases >5 and ≤10;
- metastases diameter ≤ 5 cm;
- intrahepatic tumors ≤5, and tumor burden ≤1/2 liver volume;
Key exclusion criteria (8 listed)
- under 18 years or over 75 years;
- metastases >10
- non-lung metastases;
- incomplete clinical data;
- metastases diameter > 5 cm;
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 |
|---|---|---|
| CadonilimabCadonilimab, 375mg，Q3W， IV | Drug | Bevacizumab+Cadonilimab group, Cryoablation+Bevacizumab+Cadonilimab |
| BevacizumabBevacizumab, 7.5mg/kg，Q3W， IV | Drug | Bevacizumab+Cadonilimab group, Cryoablation+Bevacizumab+Cadonilimab |
| CryoablationPatients accepted Cryoablation of pulmanary metastases | Procedure or surgery | Cryoablation+Bevacizumab+Cadonilimab |
Primary outcome
Objective response rate (ORR)
Time frame: 6 months
ORR, as determined based on tumor response according to RECIST 1.1, is defined as partial response and complete response.
2 secondary outcomes
Progression free survival (PFS)
Time frame: 6 months
Overall survival (OS)
Time frame: 12 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 20 Feb 2024.
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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.
Zhimei Hunag, MD study director
Sun Yat-sen University
Jinhua Huang, MD study director
Sun Yat-sen University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cadonilimab, Bevacizumab and Cryoablation in people with Hepatocellular Carcinoma and Liver Cancer Stage IV, run by Sun Yat-sen University at 2 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 12 inclusion and 8 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: looking for participants now, as of the sponsor's last update on 20 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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 Qunfang Zhou, MD (86 19868000115, zhouqun988509@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective response rate (ORR) (time frame: 6 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 20 Feb 2024.