Hepatocellular Carcinoma
Conditions
Brief summary
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
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.
Interventions
RADIATIONProton Beam Therapy
\- 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
Sponsors
National Cancer Center, Korea
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| local progression-free survival | Up to 1 year | To evaluate the local progression-free survival (LPFS) in HCC patients treated with hypofractionated proton beam radiotherapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| overall survival | Up to 2years until study closed | * 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 |
Countries
South Korea
Outcome results
None listed