Hypofractionated Proton Beam Radiotherapy for Inoperable Hepatocellular Carcinoma

Study Overview
=================
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.

Official Title
-----------------
A Phase II Study Using Hypofractionated Proton Beam Radiotherapy for Inoperable Hepatocellular Carcinoma

Conditions
-----------------
Hepatocellular Carcinoma

Intervention / Treatment
-----------------
* Radiation: Proton Beam Therapy


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Proton Beam Therapy<br>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 | Radiation: Proton Beam Therapy<br>* 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<br>* Other names: Radiotherapy;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | Up to 5 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | Up to5 years until study closed |