Clinical trial NCT05433701: Stereotactic Body Radiotherapy Versus Radiofrequency Ablation for Unresectable, Small (≤ 3 cm) HCC
Official title: A Phase III Randomized Controlled Non-inferiority Trial to Compare Stereotactic Body Radiotherapy Versus Radiofrequency Ablation for Unresectable, Small (≤ 3 cm) Hepatocellular Carcinoma
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Hepatocellular Carcinoma
Lead sponsor: Asan Medical Center
Sponsor class: OTHER
First posted: 2022-06-27
Enrollment: 178
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality and the sixth most prevalent cancer in the world. Standard treatments for early-stage HCCs include resection, liver transplantation, and percutaneous ablation, with 5-year survival rates of over 50 percent. Less than one-third of patients, however, are candidates for hepatic resection, and the use of radiofrequency ablation (RFA) may be significantly limited in cases with unfavorable tumor location and poor visibility on images, which increase the risk of technical failures and complications after RFA.

Recent advancements in radiotherapy and imaging have made it possible to deliver optimal radiation doses on the tumor site while minimizing exposure to normal organs. Stereotactic body radiation therapy (SBRT) is a method of high-precision radiation therapy that concentrates high-dose radiation to HCC in a short period of time to maximize the therapeutic effect on the tumor and minimize the side effects on normal tissues. Prospective and retrospective studies on SBRT for HCC have demonstrated its efficacy for local tumor control in small HCC. On the basis of these promising clinical results, a number of studies have compared the efficacy of RFA and SBRT. However, there is no strong evidence from randomized controlled trials comparing SBRT and RFA.

In order to evaluate and compare the local efficacy and clinical outcomes of SBRT and RFA in patients with recurrent HCC, we conduct this non-inferiority trial.

Detailed description: A total of 178 subjects are randomly assigned to one of two treatment groups (89 patients in the body stereotactic radiotherapy group and 89 patients in the radiofrequency ablation group). If the assigned treatment method is technically infeasible, patients are allowed to be treated with the other method.

* RFA: When localization of the lesion is difficult under image guidance, when it is difficult to secure a safe needle path, when there is a risk of collateral thermal damage to adjacent organs, and when it is difficult to prevent it.
* SBRT: When irradiation with 45 Gy (daily dose of 15 Gy) is infeasible due to the maximum tolerance dose of normal organs.

Eligibility criteria: Inclusion Criteria:

1. patient over the age of 18
2. primary or recurrent HCC that is not suitable for surgery
3. HCCs with a longest diameter of ≤3cm and ≤2 lesions
4. no evidence of intrahepatic or extrahepatic residual disease except for target lesions
5. Child-Pugh class A or B hepatic function
6. no macroscopic vascular invasion or extrahepatic metastasis
7. written informed consent

Exclusion Criteria:

1. Eastern Cooperative Oncology Group performance status score 3 or 4
2. uncontrolled ascites, variceal bleeding, or hepatic encephalopathy
3. previous history of liver transplantation
4. an active gastric or duodenal ulcer within 3 months before screening
5. pregnant woman
6. uncontrolled other malignancies except for HCC within 2 years before screening
7. platelet count \<50,000/µl
8. Patients who are judged by the researcher to be difficult to conduct clinical research

Primary outcomes:
measure: Local progression-free survival rate, per-protocol (PP)
timeFrame: At year 2
Secondary outcomes:
measure: Progression-free survival rate, intention-to-treat (ITT)
timeFrame: At year 2
measure: Overall survival rate, ITT
timeFrame: At year 2
measure: Intrahepatic progression-free survival rate, PP
timeFrame: At year 2
measure: Intrahepatic progression-free survival rate, ITT
timeFrame: At year 2
measure: Progression-free survival rate, PP
timeFrame: At year 2
measure: Progression-free survival rate, ITT
timeFrame: At year 2
measure: Adverse reaction rate, PP
timeFrame: At year 2
measure: Adverse reaction rate, ITT
timeFrame: At year 2
measure: Adverse reaction rate ≥ Gr 3, PP
timeFrame: At year 2
measure: Adverse reaction rate ≥ Gr 3, ITT
timeFrame: At year 2
measure: Change of Child-Pugh score , PP
timeFrame: At year 2
measure: Change of Child-Pugh score, ITT
timeFrame: At year 2
measure: Local progression-free survival rate according to the tumor location, PP
timeFrame: At year 2
measure: Local progression-free survival rate according to the tumor location, ITT
timeFrame: At year 2
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
Study officials:
affiliation: Asan Medical Center
name: Jonggi Choi, M.D, Ph D
role: PRINCIPAL_INVESTIGATOR
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