RFA Versus SBRT for Recurrent Small HCC

NCT04047173 | Completed Phase 3

• 1 other identifier: RFA vs. SBRT for recurrent HCC
• Study Type: interventional
• Target: 166
• Locations: 1 country
• Sites: 1

Brief Summary

Recurrence rate of hepatocellular carcinoma (HCC)after resection is as high as 65.0%-83.7%.The recurrence of HCC is the most important factor affecting prognosis. Reasonable and effective treatment of recurrent lesion can significantly improve the long-term treatment efficacy of HCC. The recurrent lesion is usually detected when it's small and is the best indication for local treatment. Local ablation therapy represented by radiofrequency ablation (RFA) is one of the main treatments for recurrent small HCC. Our previous study showed that for recurrent small HCC(≤5cm), RFA has the efficacy equivalent to re-excision, with the advantages of small trauma, quick recovery, low cost, and high quality of life. With the advancement of radiotherapy equipment and the development of precise radiotherapy technology, stereotactic radiotherapy (SBRT) has become one of the routine treatments for HCC, especially for small HCC. Retrospective controlled studies have shown that SBRT is similar to RFA in treating small HCC, and the local control rate may be better than RFA. This project is to conduct a prospective, open, randomized, controlled clinical study of RFA versus SBRT for the treatment of recurrent small hepatocellular carcinoma (single lesion ≤ 5 cm, without extra-hepatic metastasis or vascular invasion). The primary endpoint is local progression-free survival (LPFS), and secondary endpoints are progression-free survival (PFS), overall survival (OS), local control rate (LCR), and safety. Data analysis will be performed according to intention-to-treat (ITT) principles. Subgroup analyses will be conducted according to the predefined stratification factor (tumor diameter ≤ 2 cm vs. 2-5 cm) and other baseline characteristics. The results of these study will help to further improve the long-term treatment efficacy of HCC and establish a rational and effective treatment model for HCC.

Conditions

Hepatocellular Carcinoma

Keywords

recurrent small hepatocellular carcinoma; Radiofrequency Ablation; Stereotactic Body Radiotherapy

Outcome Measures

Primary Outcomes (1)

• Local progression-free survival (LPFS)

  LPFS is defined as the time from randomization to local tumor progression or death from any cause. Local tumor progression was defined as progressive disease occurring within 1 cm of the margin of the ablation region or within 1 cm of the margin of the PTV for SBRT.

  From date of randomization until the date of first documented local tumor progression or date of death from any cause, whichever came first, assessed up to 2 years.

Secondary Outcomes (4)

• Progression-free survival (PFS)

  From date of randomization until the date of first documented tumor progression or date of death from any cause, whichever came first, assessed up to 2 years.

• Overall survival (OS)

  From date of randomization until the date of death from any cause, assessed up to 2 years.

• 1-,2-,and 3-year local control rate (LCR)

  1, 2, or 3 years after treatment completion.

• Safety and adverse events

  Acute complications are defined as adverse events occurring within 90 days after treatment; late complications are defined as adverse events occurring after 90 days of treatment completion.

Study Arms (2)

Stereotactic Body Radiotherapy (SBRT)

EXPERIMENTAL

GTV is defined as the intrahepatic lesion on images. Internal target volume (ITV) is defined as the combined volume of GTVs on 10 respiratory phases. Planning target volume (PTV) is generated by adding a 5-mm margin to the ITV. OARs include liver, kidney, stomach, small intestine, and spinal cord. Normal liver volume is defined as the entire liver minus GTV. Dose constraints to OARs were as follows: mean dose of normal liver \< 10 Gy, V15Gy (percentage of the normal liver volume receiving ≥ 15 Gy) \< 35%; kidneys Dmean \< 6 Gy; esophagus D0.5cc \< 21 Gy; stomach D0.5cc \< 21 Gy; small intestine D0.5cc \< 21 Gy; colon D0.5cc \< 24 Gy; heart D0.5cc \< 30 Gy; ribs D0.5cc \< 39 Gy; and spinal cord Dmax \< 18 Gy. SBRT is planned using volumetric arc therapy techniques with a prescription dose of 36-54 Gy in 3 fractions, irradiated every other day, and completed within one week. Cone-beam CT is performed before each treatment.

Radiation: stereotactic body radiotherapy (SBRT)

Radiofrequency Ablation (RFA)

ACTIVE COMPARATOR

RFA is performed under intravenous, epidural, or general anesthesia guided by computed tomography (CT) or ultrasound, preferably through a percutaneous or laparoscopic approach. The ablation electrode is precisely inserted into the center of the tumor and ablated at 30-50W power for 5-10 minutes depending on the size and shape of the tumor. Adequate coverage of the tumor lesion with a defined "safety margin" is ensured during ablation. After the completion of tumor ablation, the instrument will remaine active as the electrode is retracted, facilitating needle tract ablation. Contrast-enhanced CT, MRI, and ultrasonography will be performed one month after RFA to detect residual disease. Patients with confirmed complete ablation will undergo periodic follow-up, whereas those with residual tumors undergo repeat RFA procedures. Persistent tumor residue after two consecutive RFA sessions is deemed a treatment failure, and RFA treatment will be discontinued.

Procedure: Radiofrequency ablation (RFA)

Interventions

stereotactic body radiotherapy (SBRT) RADIATION

Radiotherapy dose is 36-54 Gy, irradiated in 3 times, every other day, completed within 1 week.

Stereotactic Body Radiotherapy (SBRT)

Radiofrequency ablation (RFA) PROCEDURE

RFA with a safe margin, RFA again if residual, no more than 2 times.

Radiofrequency Ablation (RFA)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18-75 years;
• Diagnosed with HCC: The diagnosis of HCC will be confirmed according to the " Chinese Guidelines for the Diagnosis and Treatment of Hepatocellular Carcinoma (2019 Edition) " formulated by the National Health Commission of China and the Barcelona Clinic Liver Cancer (BCLC) strategy for prognosis prediction and treatment recommendation of the European Association for the Study of the Liver (EASL);
• Recurrent small HCC: Single hepatocellular carcinoma ≤ 5 cm that recurs after previous curative resection or thermal ablation, with the recurrence time ≥ 3 months from resection/ablation, and without extrahepatic metastasis or vascular invasion at recurrence;
• No contraindications for RFA and SBRT treatment;
• Karnofsky performance score (KPS) ≥ 90;
• Liver function Child-Pugh class A;
• Normal liver volume greater than 800 cm3;
• Expected survival time longer than 6 months;
• The function of important organs meets the following requirements: a. white blood cell ≥ 3×109/L; b. hemoglobin ≥ 80 g/L; c. platelets ≥ 50×109/L; d. blood creatinine ≤ 1.5 times the upper limit; e. prothrombin time (PT) ≤ 3 seconds above control;
• Subject has signed the informed consent form and agreed to the treatment and follow-up schedules according to this protocol;
• Subject must have the ability to understand and voluntarily sign the written informed consent form prior to starting any specific procedure in the study.

You may not qualify if:

• Presence of extrahepatic metastasis or intrahepatic vascular invasion;
• More than one recurrent lesion, or maximum diameter \> 5 cm;
• Concomitant severe cardiac, pulmonary, renal, or other major organ dysfunction, severe infection or other comorbidities, unable to tolerate treatment;
• History of other malignancies;
• History of allergic reactions to relevant drugs;
• History of organ transplantation;
• During pregnancy or lactation;
• Unable to undergo one of the treatments (RFA or SBRT);
• Concomitantly receiving other anti-tumor therapy (including immunotherapy and targeted therapy);
• Other factors that may affect patient enrollment and evaluation results;
• Refusal to comply with the study protocol requirements for follow-up and refusal to sign the informed consent form.

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

Location

Related Publications (14)

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  PMID: 39693584 DERIVED

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Radiosurgery; Radiofrequency Ablation

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques; Radiofrequency Therapy; Ablation Techniques

Study Officials

• Zhang Yao-Jun, MD.

  Sun Yat-sen University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Pro.

Study Record Dates

• First Submitted: August 4, 2019
• First Posted: August 6, 2019
• Study Start: August 12, 2019
• Primary Completion: April 1, 2024
• Study Completion: April 1, 2024
• Last Updated: June 17, 2024

Record last verified: 2024-06

Locations

CN (1)