Comparison Between Radiofrequency Ablation and Hypofractionated Proton Beam Radiation for Recurrent/Residual HCC

Study Overview
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Brief Summary
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This phase 3 study is to evaluate the effectiveness of the comparison between radiofrequency ablation and hypofractionated proton beam radiation.

Detailed Description
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The sample size for this study was based on a non-inferiority design. Primary objective: estimate local progression-free survival (LPFS) rate in two treatments Primary endpoint: 2-year LPFS rate Expected 2-year LPFS rate in the RFA: 85% Accural time and follow up time: 24 months and 24 months, respectively. Precision for 2-year LPFS rate estimation: Allowing a difference of 15% as the non-inferiority margin, with a power of 80% and a type I error level of 5%, evaluable 68 patients are required. Considering 5% of follow-up loss, we need 72 patients in each arm, so a total of 144 patients will be enrolled.

Official Title
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A Randomized Phase III Study of the Comparison Between Radiofrequency Ablation and Hypofractionated Proton Beam Radiation in Patients With Recurrent/Residual Small Hepatocellular Carcinoma (APROH Study)

Conditions
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Recurrent Small Hepatocellular Carcinoma, Residual Small Hepatocellular Carcinoma

Intervention / Treatment
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* Procedure: radiofrequency ablation
* Radiation: Proton beam therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HCC diagnosed as (i) the presence of risk factors including hepatitis B or C virus and liver cirrhosis, a serum a-fetoprotein (AFP) level greater than 200 IU/ml and a radiologically compatible feature with HCC in one or more CT/MRI/angiograms, or (ii) the presence of risk factors including hepatitis B or C virus and liver cirrhosis, a serum a-fetoprotein (AFP) level less than 200 IU/ml, and a radiologically compatible feature with HCC in two or more CT/MRI/angiograms or (iii) histological confirmation HCC patients who had recurrent or residual tumor after other treatments without evidence of extrahepatic metastasis the largest diameter of tumor should be less than 3cm, and the number of tumor ≤2 no previous treatment to target tumors by other forms of RT liver function of Child-Pugh class A or B7 (Child-Pugh score of ≤7) Age of ≥18 years performance status of 0 to 2 on the Eastern Cooperative Oncology Group (ECOG) score WBC count ≥ 2,000/mm3; hemoglobin level ≥ 7.5 g/dL; platelet count ≥ 50,000/mm3; and adequate hepatic function (total bilirubin ≤ 3.0 mg/dL; AST and ALT < 5.0× upper limit of normal; no ascites) no serious comorbidities other than liver cirrhosis written informed consent Exclusion Criteria: evidence of extrahepatic metastasis age < 18 years liver function of Child-Pugh class B8-9 and C (Child-Pugh score of >7) or uncontrolled cases of active chronic hepatitis B previous history of other forms of RT adjacent to target tumors poor performance status of 3 to 4 on the Eastern Cooperative Oncology Group (ECOG) score pregnant or breast feeding status previous history uncontrolled other malignancies within 2 years

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A(radiofrequency ablation )<br>radiofrequency ablation | Procedure: radiofrequency ablation<br>* * RFA(radiofrequency ablation ) RFA electrode: Cool-tip RF ablation system (Covidien plc, 20 Lower Hatch Street Dublin 2, Ireland) and Well-Point RF Electrode (STARmed, Koea) performed using either the manufacturer's standard algorithm or an interactive algorithm, with the latter being used when the impedance did not begin to increase at the midinterval of the standard algorithm the duration of a single RFA session was 10 min to 15 min.<br>|
| Experimental: B(Proton)<br>hypofractionated proton beam therapy | Radiation: Proton beam therapy<br>* * Proton 66 GyE /10 fx, 6.6 GyE fraction dose, 5 days/week, for HCC free from the alimentary tract (i.e., stomach, duodenum, esophagus, small and large bowel) (more than 2cm from clinical target volume),TLV30<40%,and/orRLV30<30%)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| local progression-free survival(LPES) | To evaluate the local progression-free survival for 2 years | up to 2 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| disease-free survival (DFS) | Disease-free survival was defined as the interval from the date of randomization to date of detection study closed | up to 2 years until study closed | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hepatocellular, Proton, RFA