Radiofrequency Ablation Plus Systematic Neoadjuvant Therapy for Recurrent Hepatocellular Carcinoma (RANT Study)

NCT ID: NCT05277675

Last Updated: 2022-03-14

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 160 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-11-01
• Study Completion Date: 2023-10-30

Brief 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 overall survival (OS)

2. 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.

Conditions

Hepatocellular Carcinoma Recurrent

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Neoadjuvant therapy+ RFA

After confirmation of HCC recurrence by imaging exam, subjects will receive neoadjuvant therapy (immune checkpoint inhibitors + targeted therapy) and then RFA

Group Type: EXPERIMENTAL

Tislelizumab/Sintilimab+Lenvatinib/Bevacizumab

Intervention Type: DRUG

Immune checkpoint inhibitor (tislelizumab/sintilimab) combined with anti-angiogenic drugs (lenvatinib/bevacizumab) used as neoadjuvant therapy

RFA

Intervention Type: PROCEDURE

RFA will be performed in a percutaneous way guided contrast enhanced ultrasound.

RFA alone

After confirmation of HCC recurrence by imaging exam, subjects will receive RFA treatment only.

Group Type: ACTIVE_COMPARATOR

RFA

Intervention Type: PROCEDURE

RFA will be performed in a percutaneous way guided contrast enhanced ultrasound.

Interventions

Tislelizumab/Sintilimab+Lenvatinib/Bevacizumab

Immune checkpoint inhibitor (tislelizumab/sintilimab) combined with anti-angiogenic drugs (lenvatinib/bevacizumab) used as neoadjuvant therapy

Intervention Type: DRUG

RFA

RFA will be performed in a percutaneous way guided contrast enhanced ultrasound.

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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;
• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Southwest Hospital, China

OTHER

Sponsor Role: lead

Responsible Party

fengkai

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Institute of hepatobiliary surgery,Southwest Hospital

Chongqing, Chongqing Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Kai Feng, MD,PhD

Role: CONTACT

fengkai7688@hotmail.com

+86-13228683383

Kuansheng Ma, MD,PhD

Role: CONTACT

kuanshengma@outlook.com

+86-15213249505

Facility Contacts

Kai Feng, M.D

Role: primary

fengkai7688@hotmail.com

+86-23-13228683383

Other Identifiers

(A)KY2021083

Identifier Type: -

Identifier Source: org_study_id