Hypofractionated Proton Beam Radiotherapy for Inoperable Hepatocellular Carcinoma
Primary Purpose
Hepatocellular Carcinoma
Status
Completed
Phase
Not Applicable
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Proton Beam Therapy
Sponsored by

About this trial
This is an interventional treatment trial for Hepatocellular Carcinoma
Eligibility Criteria
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
Sites / Locations
- National Cancer Center, Korea
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Proton Beam Therapy
Arm Description
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
Outcomes
Primary Outcome Measures
local progression - free survival
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
overall survival
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)
Full Information
NCT ID
NCT02395523
First Posted
March 17, 2015
Last Updated
July 5, 2020
Sponsor
National Cancer Center, Korea
1. Study Identification
Unique Protocol Identification Number
NCT02395523
Brief Title
Hypofractionated Proton Beam Radiotherapy for Inoperable Hepatocellular Carcinoma
Official Title
A Phase II Study Using Hypofractionated Proton Beam Radiotherapy for Inoperable Hepatocellular Carcinoma
Study Type
Interventional
2. Study Status
Record Verification Date
July 2020
Overall Recruitment Status
Completed
Study Start Date
March 5, 2015 (Actual)
Primary Completion Date
March 26, 2020 (Actual)
Study Completion Date
May 18, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
National Cancer Center, Korea
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatocellular Carcinoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
45 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Proton Beam Therapy
Arm Type
Experimental
Arm Description
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
Intervention Type
Radiation
Intervention Name(s)
Proton Beam Therapy
Other Intervention Name(s)
Radiotherapy
Intervention Description
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 Measure Information:
Title
local progression - free survival
Description
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)
Time Frame
Up to 5 year
Secondary Outcome Measure Information:
Title
overall survival
Description
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)
Time Frame
Up to5 years until study closed
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tae Hyun Kim, Ph.D
Organizational Affiliation
National Cancer Center, Korea
Official's Role
Principal Investigator
Facility Information:
Facility Name
National Cancer Center, Korea
City
Goyang-si
State/Province
Gyeonggi-do
ZIP/Postal Code
411-769
Country
Korea, Republic of
12. IPD Sharing Statement
Learn more about this trial
Hypofractionated Proton Beam Radiotherapy for Inoperable Hepatocellular Carcinoma
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