Hypofractionated Proton Beam Radiotherapy for Hepatocellular Carcinoma

Study Overview
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Brief Summary
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This phase II study is to evaluate the effectiveness of hypofractionated proton beam therapy (PBT) for HCC patients in hepatitis B endemic area.

Detailed Description
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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 for each arms will be enrolled.

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

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* 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 were not prospective suitable or refused for any other treatment, such as surgery or local ablation therapy, or recurrent or residual tumor after other treatments. without evidence of extrahepatic metastasis All target tumors must be encompassable within single irradiation field (15x15 cm maximum) 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 ≥ 25,000/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) 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 multicentric HCCs, except for those with the following two conditions: *multinodular aggregating HCC that could be encompassed by single clinical target volume and within single irradiation field (15x15 cm maximum) *lesions other than targeted tumor that were judged as controlled with prior surgery and/or local ablation therapy.

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Proton Beam Therapy<br>Prescription dose to PTV as according to the following dose escalation schema: Arml 1: 60 GyE /10 fx, 6GyE 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/or RLV30 <30%) Arm 2: 50 GyE /10 fx, 5GyE fraction dose, 5 days/week, for HCC close to the alimentary tract (less than 2cm from clinical target volume) but not contact with the alimentary tract, TLV30<50% and RLV30<40% Arm 3: 35 GyE /10 fx, 4GyE fraction dose, 5 days/week, for HCC contact to the alimentary tract (contact with clinical target volume), TLV30<60%, and/or RLV30<50% Dose prescription : 95% isodose volume of prescribed dose encompassed PTV | Radiation: Proton Beam Therapy<br>* - Prescription dose to PTV as according to the following dose escalation schema: Arml 1: 60 GyE /10 fx, 6GyE 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/or RLV30 <30%) Arm 2: 50 GyE /10 fx, 5GyE fraction dose, 5 days/week, for HCC close to the alimentary tract (less than 2cm from clinical target volume) but not contact with the alimentary tract, TLV30<50% and RLV30<40% Arm 3: 35 GyE /10 fx, 4GyE fraction dose, 5 days/week, for HCC contact to the alimentary tract (contact with clinical target volume), TLV30<60%, and/or RLV30<50% - Dose prescription : 95% isodose volume of prescribed dose encompassed PTV<br>* Other names: Radiotherapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| local progression-free survival | To evaluate the local progression-free survival (LPFS) in HCC patients treated with hypofractionated proton beam radiotherapy. | Up to 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival | To evaluate compliance of proton beam radiotherapy for HCC by analyzing acute and late treatment-related toxicity, such as radiation-induced hepatic toxicity and gastrointestinal tract toxicity To evaluate the impact of hypofractionated proton beam radiotherapy for HCC by analyzing the tumor response rate, local disease-free survival (DFS) and overall survival (OS) rate | Up to 2years until study closed |