A National Phase II Study of Proton Therapy in Hepatocellular Carcinoma
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 50
- 试验地点
- 6
- 主要终点
- Number of deaths of any cause
研究概览
简要总结
350 new cases of hepatocellular carcinoma (HCC) are diagnosed in Denmark each year, but the overall prognosis is poor with a 1-year survival rate of less than 40% and a 5-year survival rate of 10% for the entire patient group.
This national phase II non-randomized single-arm study of proton therapy in HCC is conducted with the aim to offer a safe and efficient radiation treatment to fragile patients with reduced dose to the normal liver compared to conventional photon-based radiotherapy.
详细描述
Each year, approximately 350 new cases of hepatocellular carcinoma (HCC) are diagnosed in Denmark, but the overall prognosis is poor with a 1-year survival rate of less than 40% and a 5-year survival rate of 10% for the entire patient group.
This national phase II non-randomized single-arm study of proton therapy in HCC is conducted with the aim to offer a safe and efficient radiation treatment to fragile patients with reduced dose to the normal liver compared to conventional photon-based radiotherapy. The study aims to offer curative treatment to a larger group of patients and thus better prognosis for these patients.
The study will include 50 patients enrolled within 3 years. Patients cannot be guaranteed any direct personal benefits of participating in the trial. Participating in the study can help with new knowledge that can benefit future patients with similar illness.
The treatment will be given at the Danish Center for Particle Therapy. During radiotherapy, additional CT scans will be performed weekly as part of quality assurance until it can be documented that there is no such need.
Participation in the study will also mean additional examinations and questionnaires at the start of treatment, below treatment and at follow-up.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with HCC based on classical radiologic findings as defined by the American Association for the Study of Liver Diseases (AASLD) criteria or verified by biopsy
- •No extra-hepatic disease
- •Deemed ineligible for resection or Radiofrequency Ablation (RFA), or the patients should refuse RFA or surgery
- •Age ≥ 18 years
- •Performance status ≤ 2
- •Total diameter of tumor(s) ≤ 12 cm and a maximum of 3 tumors
- •Adequate liver function as measured by Child-Pugh score (Child-Pugh score ≤ 8), or absence of cirrhosis
- •Has recovered adequately from toxicity and/or complications from any previous local interventions
- •Patients with past or ongoing hepatitis C infection are allowed, but treatment for hepatitis C must have been completed one month before study entry
- •Patients with hepatitis B infection is allowed if antiviral therapy have been given for at least 4 weeks and Hepatitis B Virus (HBV) viral load is less than 100 IU/ml. The active therapy must continue throughout the radiation therapy. Patients who are Total hepatitis B core antibody (anti-HBc)(+), negative for Hepatitis B surface antigen (HbsAg) and negative or positive for Hepatitis B surface antibody (anti-HBs) with a HBV viral load under 100 IU/mL do not require HBV anti-viral prophylaxis
- •Adequate organ function
- •hematological: hemoglobin ≥ 6 mmol/l, absolute neutrophil count (ANC) ≥ 1,5 x 109/L, platelets ≥ 50 x 109/L
- •hepatic: bilirubin ≤ 1.5 x ULN, alanin-aminotransferase (ALAT) ≤ 1.5 x ULN
- •renal: creatinine ≤ 1.5 x ULN
- •Ability to adhere to procedures for study and follow-up
- •Signed informed consent to participate
- •Final decisions on inclusion and treatment with proton therapy are at the discretion of the investigator
排除标准
- •Previous x-ray-based radiotherapy in the liver
- •Child Pugh score >8
- •Tumor less than 1 cm from any critical organs at risk (OAR) (duodenum, kidney, stomach, intestines).
- •Previous Selective internal radiation therapy (SIRT)
- •Episode of hepatic encephalopathy within the last 6 months
- •Uncontrolled ascites with need for drainage > 1 per month
- •Episode of bleeding esophageal varices within the past month. If active bleeding from esophageal varices has occurred, a gastroscopy should be performed 4 weeks after the bleeding episode to ensure maximum grade 1 varices.
- •Patients with metal implants where beam entrance through the metal implants cannot be avoided (not applicable for fiducial markers implanted for radiotherapy use)
- •Patients for whom it is not possible to produce a robust treatment plan following the technical guidelines (Appendix A)
- •Patients for whom it is not possible to implant fiducial markers e.g. due to insufficient coagulation of the blood.
结局指标
主要结局
Number of deaths of any cause
时间窗: 4 months after start of radiotherapy
Death of any cause
Number of participants with Radiation-induced liver disease (RILD)
时间窗: 4 months after start of radiotherapy
Worsening of the Child- Pugh score ≥2 or alanin-aminotransferase (ALAT) ≥5 upper normal limit (ULN)
次要结局
- Pattern of failure(Until 5 years after start of radiotherapy)
- Number of participants with RILD within 6 months of start of radiotherapy(6 months after start of radiotherapy)
- Reduction in mean liver dose(up to 5 years)
- Quality of Life HCC-18(Until 60 months after start of radiotherapy)
- Overall survival(3 years after start of radiotherapy)
- Technical feasibility(up to 5 years)
- Health-related Quality of Life C30(Until 60 months after start of radiotherapy)
- Acute toxicity(4 months after start of radiotherapy)
- Late toxicity(from 4 months until 60 months after start of radiotherapy)
- Radiation-induced hospitalization(within 4 months after start of radiotherapy)
- Local control(3 years after start of radiotherapy)
- Progression-free survival(3 years after start of radiotherapy)