Hepatocellular Carcinoma RecurrentRANTNCT05277675
Radiofrequency Ablation Plus Systematic Neoadjuvant Therapy for Recurrent Hepatocellular Carcinoma (RANT Study)
A study testing Tislelizumab/Sintilimab+Lenvatinib/Bevacizumab and RFA in people with Hepatocellular Carcinoma Recurrent, run by Southwest Hospital, China at 1 site in China.
Trial summary
1. To compare systemic neoadjuvant therapy (combination of immune checkpoint inhibitors and anti-angiogenic drugs (short for "targeted-immune therapy") combined with radiofrequency ablation (RFA) and RFA alone in the treatment of recurrent hepatocellular carcinoma(HCC) in 1-year recurrence-free survival (RFS) and… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Hepatocellular Carcinoma Recurrent
- What is being tested?
- Tislelizumab/Sintilimab+Lenvatinib/Bevacizumab and RFA
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 160 participants
- Where
- 1 siteChina
- Study dates
- 1 Nov 2021to 30 Oct 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
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
- Research subjects understand the research content and significance, and provide the written informed consent;
- age 18 - 75 years and gender is not limited;
- a history of liver resection or RFA for HCC which was clinically or pathologically diagnosed according to the standard of the American Association for the Study of Liver Diseases; the number of lesions ≤ 3, the largest lesion ≤ 3 cm, as demonstrated on by contrast enhanced CT/MRI;
- Patients who are unable or unwilling to undergo liver resection, and have not received other anti-tumor therapies before detection of the recurrence;
- Child Pugh A (≤ 7 points), no pleural ascites and hepatic encephalopathy requiring treatment; Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0-1;
- Within 7 days before enrollment, have sufficient liver and kidney function, suitable laboratory indicators (untreated): hemoglobin (HGB) ≥ 9.0 g/dl, neutrophils ≥ 1,500/mm3, PLT ≥ 50×109/L, serum ALB ≥ 28 g/L, TBIL < 50 umol/L, ALT, AST < 5 times the upper limit of normal, Bun, Cr < 1.5 times the upper limit of normal, INR < 1.7 or prolonged PT < 4 s;
- Consent to take the immune checkpoint inhibitor and molecular-targeted drugs;
- No other diseases affecting RFA treatment and targeted therapy combining with immune checkpoint inhibitors.
Who cannot join
- Patients who have a history of immune checkpoint inhibitor or targeted therapy;
- Tumor invades the branch or trunk of portal vein;
- Patients with extrahepatic metastasis;
- Patients who have an active autoimmune disease or a history of autoimmune disease, hyperthyroidism or hypothyroidism, asthma requiring bronchodilator treatment.
- Patients who have significant cardiovascular disease (heart failure grade Ⅲ or higher as defined by the New York Heart Association), myocardial infarction, unstable arrhythmia, unstable angina pectoris that occurred within 3 months before treatment;
- Patients who have a history of idiopathic pulmonary fibrosis, organizing pneumonia (such as bronchiolitis obliterans), drug-induced pneumonia, idiopathic pneumonia, or an evidence of active pneumonia during chest CT scan screening;
Show all 9Show fewer
- Patients who have received allogeneic stem cell or solid organ transplantation (including liver transplantation);
- Patients who have taken any anti-tumor Chinese herbal medicine within 7 days before enrollment;
- Patients who have any other diseases, metabolic disorders, abnormal results of physical examination or laboratory tests, which may lead to contraindication to the use of the experimental drugs, or affect the reliability of the research results, or leave the patient at high risk of treatment complications, or affect patient compliance.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Institute of hepatobiliary surgery,Southwest Hospital
Chongqing, Chongqing Municipality, 400038
Kai Feng, M.D, +86-23-13228683383, fengkai7688@hotmail.com
Kai Feng, M.D
About this study
Official title: A Prospective Study of Radiofrequency Ablation Combined With Systematic Neoadjuvant Therapy in the Treatment of Recurrent Hepatocellular Carcinoma
- To compare systemic neoadjuvant therapy (combination of immune checkpoint inhibitors and anti-angiogenic drugs (short for "targeted-immune therapy") combined with radiofrequency ablation (RFA) and RFA alone in the treatment of recurrent hepatocellular carcinoma(HCC) in 1-year recurrence-free survival (RFS) and overall survival (OS)
- To evaluate the clinical value of systemic neoadjuvant therapy (i.e. immune checkpoint inhibitors and targeted therapy) combined with RFA in the treatment of recurrent HCC, as well as the safety and efficacy of this strategy.
Read the detailed description
RFA is an important minimally invasive approach for recurrent HCC treatment, but is hampered by the high recurrence rate and limited ablation volume for the tumor. Therefore, the key to improving the efficacy of RFA is to maximize the complete ablation zone of tumor lesions and the killing of residual cancer cells. In recent years, due to the unique advantages of immune checkpoint inhibitors(ICIs), immunotherapy has gradually become a vital part of neoadjuvant therapy, and the scope of immunotherapy in malignant tumors expands. With administration of ICIs, revived tumor-specific CD8+ T cells proliferate and kill existing tumor cells and recirculate into the blood. After resection or ablation of the primary tumor, the remaining circulating tumor-specific CD8+ T cells and T cell clones present in the metastatic site can retain long-term anti-tumor immunity and play a vital role in continuous killing of residual cancer cells and immune surveillance. At present, the combination of targeted therapy and immune checkpoint inhibitors has achieved a higher objective response rate (ORR) and disease control rate (DCR) in the treatment of in treatment of HCC, which provides a reliable theoretical and practical basis for using as a strategy of neoadjuvant therapy.
The current reports on neoadjuvant therapy for HCC are limited to patients who are going undergo surgical resection, and there is no report on the neoadjuvant therapy prior to RFA. Since molecular targeted drugs generally have anti-angiogenic effects, drug withdrawal for two weeks or more (bevacizumab should be stopped for at least 4 weeks) before surgery is required to reduce the risk of intraoperative bleeding caused by targeted drugs and the hard-to-heal incision after operation. The longer-term drug withdrawal will prolong the preoperative waiting period, and the tumor may progress, leaving the patients loss of the opportunity for surgery. However, due to its advantage of minimal invasiveness, patients can undergo RFA directly without drug withdrawal.
- Conditions
- Hepatocellular Carcinoma Recurrent
- Being tested
- Tislelizumab/Sintilimab+Lenvatinib/Bevacizumab, RFA
- Keywords
- immune checkpoint inhibitors, targeted therapy, neoadjuvant therapy, radiofrequency ablation, hepatocellular carcinoma, recurrence
- Medical subject headings
- Carcinoma, Hepatocellular, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tislelizumab/Sintilimab+Lenvatinib/BevacizumabDrug
Immune checkpoint inhibitor (tislelizumab/sintilimab) combined with anti-angiogenic drugs (lenvatinib/bevacizumab) used as neoadjuvant therapy
RFAProcedure or surgery
RFA will be performed in a percutaneous way guided contrast enhanced ultrasound.
| Study group | Role | What they receive |
|---|---|---|
| Neoadjuvant therapy+ RFA | Experimental | After confirmation of HCC recurrence by imaging exam, subjects will receive neoadjuvant therapy (immune checkpoint inhibitors + targeted therapy) and then RFA Receives: Drug: Tislelizumab/Sintilimab+Lenvatinib/Bevacizumab; Procedure: RFA |
| RFA alone | Active comparator | After confirmation of HCC recurrence by imaging exam, subjects will receive RFA treatment only. Receives: Procedure: RFA |
What is being measured
The primary outcome is the main question the study is designed to answer.
1-year recurrence-free survival
Evaluated by hepatic imaging examination (contrast-enhanced US/CT/MRI) at early stage combined with AFP and PIVKA-Ⅱtests.
Measured: 1 year after treatment
1-year overall survival
Evaluated by hepatic imaging examination (contrast-enhanced US/CT/MRI) at early stage combined with AFP and PIVKA-Ⅱtests.
Measured: 1 year after treatment
Secondary outcomes (2)
procedure related complications
procedure related complications
Measured: up to 1 year.
immune-related adverse events
Measured: up to 1 year.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Mar 2022
- Study start1 Nov 2021
- Primary completion1 Nov 2022 (estimated)
- Study completion30 Oct 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatocellular Carcinoma RecurrentStudies 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
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 160 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Southwest Hospital, China
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, fengkai, Southwest Hospital, China
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05277675
- Sponsor's protocol ID
- (A)KY2021083
- Acronym
- RANT
- Status last verified
- Mar 2022
- First submitted
- 27 Feb 2022
- Last updated
- 14 Mar 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective Study of Radiofrequency Ablation Combined With Systematic Neoadjuvant Therapy in the Treatment of Recurrent Hepatocellular Carcinoma
- ClinicalTrials.gov ID
- NCT05277675
- Acronym / sponsor ID
- RANT / (A)KY2021083
- Conditions
- Hepatocellular Carcinoma Recurrent
- Keywords
- immune checkpoint inhibitors, targeted therapy, neoadjuvant therapy, radiofrequency ablation, hepatocellular carcinoma, recurrence
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 160 participants (estimated)
- Lead sponsor
- Southwest Hospital, ChinaUniversity, hospital or other
- Study start
- 1 Nov 2021 (actual)
- Primary completion
- 1 Nov 2022 (estimated)
- Study completion
- 30 Oct 2023 (estimated)
- First posted
- 14 Mar 2022 (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.
- To compare systemic neoadjuvant therapy (combination of immune checkpoint inhibitors and anti-angiogenic drugs (short for "targeted-immune therapy") combined with radiofrequency ablation (RFA) and RFA alone in the treatment of recurrent hepatocellular carcinoma(HCC) in 1-year recurrence-free survival (RFS) and overall survival (OS)
- To evaluate the clinical value of systemic neoadjuvant therapy (i.e. immune checkpoint inhibitors and targeted therapy) combined with RFA in the treatment of recurrent HCC, as well as the safety and efficacy of this strategy.
Detailed description
RFA is an important minimally invasive approach for recurrent HCC treatment, but is hampered by the high recurrence rate and limited ablation volume for the tumor. Therefore, the key to improving the efficacy of RFA is to maximize the complete ablation zone of tumor lesions and the killing of residual cancer cells. In recent years, due to the unique advantages of immune checkpoint inhibitors(ICIs), immunotherapy has gradually become a vital part of neoadjuvant therapy, and the scope of immunotherapy in malignant tumors expands. With administration of ICIs, revived tumor-specific CD8+ T cells proliferate and kill existing tumor cells and recirculate into the blood. After resection or ablation of the primary tumor, the remaining circulating tumor-specific CD8+ T cells and T cell clones present in the metastatic site can retain long-term anti-tumor immunity and play a vital role in continuous killing of residual cancer cells and immune surveillance. At present, the combination of targeted therapy and immune checkpoint inhibitors has achieved a higher objective response rate (ORR) and disease control rate (DCR) in the treatment of in treatment of HCC, which provides a reliable theoretical and practical basis for using as a strategy of neoadjuvant therapy.
The current reports on neoadjuvant therapy for HCC are limited to patients who are going undergo surgical resection, and there is no report on the neoadjuvant therapy prior to RFA. Since molecular targeted drugs generally have anti-angiogenic effects, drug withdrawal for two weeks or more (bevacizumab should be stopped for at least 4 weeks) before surgery is required to reduce the risk of intraoperative bleeding caused by targeted drugs and the hard-to-heal incision after operation. The longer-term drug withdrawal will prolong the preoperative waiting period, and the tumor may progress, leaving the patients loss of the opportunity for surgery. However, due to its advantage of minimal invasiveness, patients can undergo RFA directly without drug withdrawal.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Neoadjuvant therapy+ RFA | Experimental | Drug: Tislelizumab/Sintilimab+Lenvatinib/Bevacizumab, Procedure: RFAAfter confirmation of HCC recurrence by imaging exam, subjects will receive neoadjuvant therapy (immune checkpoint inhibitors + targeted therapy) and then RFA |
| RFA alone | Active comparator | Procedure: RFAAfter confirmation of HCC recurrence by imaging exam, subjects will receive RFA treatment only. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Research subjects understand the research content and significance, and provide the written informed consent;
- age 18 - 75 years and gender is not limited;
- a history of liver resection or RFA for HCC which was clinically or pathologically diagnosed according to the standard of the American Association for the Study of Liver Diseases; the number of lesions ≤ 3, the largest lesion ≤ 3 cm, as demonstrated on by contrast enhanced CT/MRI;
- Patients who are unable or unwilling to undergo liver resection, and have not received other anti-tumor therapies before detection of the recurrence;
- Child Pugh A (≤ 7 points), no pleural ascites and hepatic encephalopathy requiring treatment; Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0-1;
Key exclusion criteria (9 listed)
- Patients who have a history of immune checkpoint inhibitor or targeted therapy;
- Tumor invades the branch or trunk of portal vein;
- Patients with extrahepatic metastasis;
- Patients who have an active autoimmune disease or a history of autoimmune disease, hyperthyroidism or hypothyroidism, asthma requiring bronchodilator treatment.
- Patients who have significant cardiovascular disease (heart failure grade Ⅲ or higher as defined by the New York Heart Association), myocardial infarction, unstable arrhythmia, unstable angina pectoris that occurred within 3 months before treatment;
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 |
|---|---|---|
| Tislelizumab/Sintilimab+Lenvatinib/BevacizumabImmune checkpoint inhibitor (tislelizumab/sintilimab) combined with anti-angiogenic drugs (lenvatinib/bevacizumab) used as neoadjuvant therapy | Drug | Neoadjuvant therapy+ RFA |
| RFARFA will be performed in a percutaneous way guided contrast enhanced ultrasound. | Procedure or surgery | Neoadjuvant therapy+ RFA, RFA alone |
Primary outcome
1-year recurrence-free survival
Time frame: 1 year after treatment
Evaluated by hepatic imaging examination (contrast-enhanced US/CT/MRI) at early stage combined with AFP and PIVKA-Ⅱtests.
1-year overall survival
Time frame: 1 year after treatment
Evaluated by hepatic imaging examination (contrast-enhanced US/CT/MRI) at early stage combined with AFP and PIVKA-Ⅱtests.
2 secondary outcomes
procedure related complications
Time frame: up to 1 year.
immune-related adverse events
Time frame: up to 1 year.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Mar 2022.
Related trials for Hepatocellular Carcinoma Recurrent
RecruitingPhase 2
TACE or Ablation Combined With Sintilimab and Ipilimumab N01 as Neoadjuvant Therapy for Resectable Hepatocellular Carcinoma With Intermediate-High Recurrence Risk
Hepato Cellular Carcinoma (HCC)
Not yet recruitingPhase 1/2
A Study of MDSY-1240, a STAT3 Degrader, for the Treatment of Hematologic Malignancies and Advanced Solid Tumors
Triple-Negative Breast Cancer (TNBC), Gastric Cancer (GC)
Active, not recruitingPhase 2
Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial)
Advanced Lymphoma, Advanced Malignant Solid Neoplasm
RecruitingPhase 1/2
A Study to Evaluate the Efficacy and Safety of Ifinatamab Deruxtecan (I-DXd) in Subjects With Recurrent or Metastatic Solid Tumors (IDeate-PanTumor02)
Recurrent or Metastatic Solid Tumors
Active, not recruitingPhase 1/2
A Study to Evaluate C-CAR031 in Glypican-3 (GPC3)+ Advanced/Recurrent Hepatocellular Carcinoma (HCC)
Hepatocellular Carcinoma
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. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Tislelizumab/Sintilimab+Lenvatinib/Bevacizumab and RFA in people with Hepatocellular Carcinoma Recurrent, run by Southwest Hospital, China at 1 site 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 8 inclusion and 9 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: status not confirmed, as of the sponsor's last update on 14 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Kai Feng, MD,PhD (+86-13228683383, fengkai7688@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
1-year recurrence-free survival (time frame: 1 year after treatment). The study lists 2 primary outcomes in all. 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 14 Mar 2022.