Hypofractionated Proton Beam Radiotherapy for Inoperable Hepatocellular Carcinoma

Not Applicable

Completed

• Conditions: Hepatocellular Carcinoma
• Interventions: Radiation: Proton Beam Therapy

• Registration Number: NCT02395523
• Lead Sponsor: National Cancer Center, Korea

Brief Summary

This phase II study is to evaluate the effectiveness of hypofractionated proton beam therapy (PBT) for Hepatocellular Carcinoma patients in hepatitis B endemic area.

Detailed Description

The primary endpoint is local progression free survival. The trial is a single arm phase II trial with the historical arm. The expected 3-year local progression free survival for patient with HCC patients treated with proton beam therapy would be 80%. With a power of 80% and a type I error level of 10%, evaluable 40 patients are required to reject that the null hypothesis that true 3-year local progression free survival rate is ≤65%. Considering the 10% unevaluable patients due to loss of follow up, a total 45 eligible patients will be enrolled.

Study Timeline

• Study Start: 2015-03-05
• Study First Submitted: 2015-03-17
• Study First Submitted QC: 2015-03-17
• Study First Posted: 2015-03-23
• Primary Completion: 2020-03-26
• Study Completion: 2020-05-18
• Status Verified: 2020-07
• Last Update Submitted: 2020-07-05
• Last Update Posted: 2020-07-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 45

Inclusion Criteria

• Hepatocellular Carcinoma 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
• Inoperable HCC or refusal to surgery
• Recurrent/residual tumor after other local treatments (local ablation therapy, or transarterial chemoemobolization, etc), or unsuitable/refusal to other treatments.
• Patients without evidence of extrahepatic metastasis
• The largest diameter of tumor should be less than 7cm, and the number of tumor ≤2
• The targeted tumors is more than 2cm away from the alimentary tract (i.e., stomach, duodenum, esophagus, small and large bowel)
• 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 1 on the Eastern Cooperative Oncology Group (ECOG) score
• Required Entry Laboratory Parameters WBC count ≥ 1,500/mm3; hemoglobin level ≥ 7.5 g/dL; platelet count ≥ 30,000/mm3; and adequate hepatic function (total bilirubin ≤ 3.0 mg/dL; AST and ALT < 5.0× upper limit of normal; no uncontrolled ascites
• No serious comorbidities other than liver cirrhosis
• Signed informed consent form prior to study entry

Exclusion Criteria

• There is evidence of extrahepatic metastasis.
• Age of <18 years
• Liver function of Child-Pugh class B8-9 and C (Child-Pugh score of >7)
• Previous history of other forms of RT adjacent to target tumors
• Poor performance status of 2 to 4 on the Eastern Cooperative Oncology Group (ECOG) score
• Multicentric HCCs, except for those with the following two conditions: (i) multinodular aggregating HCC that could be encompassed by single clinical target volume and within single clinical target volume; (ii) lesions other than targeted tumor that were judged as controlled with prior surgery and/or local ablation therapy.
• Pregnant or breast feeding status
• Previous history uncontrolled other malignancies within 2 years

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Proton Beam Therapy	Proton Beam Therapy	Definition of target volume: * Gross tumor volume (GTV) = gross tumor defined using a treatment planning CT scan * Clinical target volume (CTV) = GTV + internal target volume * Planning target volume (PTV) = CTV + 5 - 7 mm of lateral, craniocaudal, and anteroposterior margins. Radiation dose and planning * Prescription dose to PTV: 70 GyE /10 fx, 7GyE fraction dose, 5 days/week * Dose prescription : 95% isodose volume of prescribed dose encompassed PTV

Primary Outcome Measures

Name	Time	Method
local progression - free survival	Up to 5 year	During PBT, patients were assessed weekly and after comletion of PBT at the 1st month, every 3months for the first 2years, every 6 months up to 5years. the tumor responses were assessed according to the modified response evaluation criteria in solid tumors criteria by comparing pre- and posst-PBT CT/MRI scans, and the severity of adverse deffects was graded using the common terminology criteria for adverse events(ver 4.0)

Secondary Outcome Measures

Name	Time	Method
overall survival	Up to5 years until study closed	During PBT, patients were assessed weekly and after com;letion of PBT at the 1st month, every 3months for the first 2years, every 6 months up to 5years. the tumor responses were assessed according to the modified response evaluation criteria in solid tumors criteria by comparing pre- and posst-PBT CT/MRI scans, and the severity of adverse deffects was graded using the common terminology criteria for adverse events(ver 4.0)

Trial Locations

Locations (1)

National Cancer Center, Korea; 🇰🇷 Goyang-si, Gyeonggi-do, Korea, Republic of