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

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)

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

Study Overview

• Status: Completed
• Conditions: Recurrent Small Hepatocellular Carcinoma; Residual Small Hepatocellular Carcinoma
• Intervention / Treatment: Procedure: radiofrequency ablation; Radiation: Proton beam therapy

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 144
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Korea, Republic of
  • Gyeonggi-do
    • Goyang-si, Gyeonggi-do, Korea, Republic of, 410-769
      • National Cancer Center, Korea

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A(radiofrequency ablation ); radiofrequency ablation	Procedure: radiofrequency ablation; * 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.
Experimental: B(Proton); hypofractionated proton beam therapy	Radiation: Proton beam therapy; * 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%)

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall survival (OS)	Overall survival(OS) was defined as the interval from the date of randomization to date of detection study closed	up to 2 years until study closed

Collaborators and Investigators

• Sponsor: National Cancer Center, Korea
• Investigators: Principal Investigator: Joong Won Park, Ph.D, National Cancer Center, Korea

Publications and helpful links

General Publications

• Kim TH, Koh YH, Kim BH, Kim MJ, Lee JH, Park B, Park JW. Proton beam radiotherapy vs. radiofrequency ablation for recurrent hepatocellular carcinoma: A randomized phase III trial. J Hepatol. 2021 Mar;74(3):603-612. doi: 10.1016/j.jhep.2020.09.026. Epub 2020 Oct 5.

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2013
• Primary Completion (Actual): January 20, 2020
• Study Completion (Actual): January 20, 2020

Study Registration Dates

• First Submitted: October 13, 2013
• First Submitted That Met QC Criteria: October 15, 2013
• First Posted (Estimate): October 16, 2013

Study Record Updates

• Last Update Posted (Actual): October 6, 2020
• Last Update Submitted That Met QC Criteria: October 4, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: RFA; hepatocellular; Proton
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Disease Attributes; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Recurrence
• Other Study ID Numbers: NCCCTS 13-695

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED