A Phase III Randomized Trial of Protons Versus Photons for Hepatocellular Carcinoma
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- NRG Oncology
- 入组人数
- 115
- 试验地点
- 50
- 主要终点
- Overall survival (OS)
研究概览
简要总结
This phase III trial studies how well radiation therapy with protons works compared with photons in treating patients with liver cancer. Radiation therapy, such as photon therapy, uses high energy x-rays to send the radiation inside the body to the tumor while proton therapy uses a beam of proton particles. Proton therapy can stop shortly after penetrating through the tumor and may cause less damage to the surrounding healthy organs and result in better survival in patients with liver cancer.
详细描述
PRIMARY OBJECTIVE:
I. To determine if overall survival (OS) is different for hepatocellular carcinoma patients treated with protons compared to photons.
SECONDARY OBJECTIVES:
I. To determine the difference in progression-free-survival (PFS) in patients with hepatocellular carcinoma (HCC) treated with protons compared to patients with HCC treated with photons.
II. To determine the difference in local progression (LP) in patients with HCC treated with protons compared to patients with HCC treated with photons.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Pathologically (histologically or cytologically) or radiographically-proven (based on the American Association for the Study of Liver Diseases [AALSD] criteria) unresectable or locally recurrent hepatocellular cancer prior to registration
- •Appropriate stage for study entry based on the following diagnostic workup:
- •All patients must have computed tomography (CT) scan chest/abdomen/pelvis with multiphasic liver CT scan prior to registration; if CT contrast is contraindicated, CT chest without contrast and magnetic resonance imaging (MRI) of abdomen is permitted
- •Participants must have measurable disease at study entry, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as > 2 cm with conventional techniques or as > 1 cm with spiral CT scan
- •Patient must have 3 or fewer single or multinodular tumors; for patients with a single lesion, lesion must be 15 cm or less in greatest dimension; for patients with two lesions, no lesion may be greater than 10 cm in greatest dimension; for patients with three lesions, no lesion may be greater than 6 cm in greatest dimension; portal vein involvement or thrombosis combined with a single lesion that is >= 1 cm and =< 15 cm in greatest dimension is allowed
- •Age >= 18
- •Zubrod performance status 0-1 within 30 days prior to registration
- •Negative urine or serum pregnancy test for women of childbearing potential within 7 days prior to study entry
- •Absolute neutrophil count (ANC) >= 1,000 cells/mm^3
- •Platelets >= 50,000 cells/mm^3
- •Hemoglobin >= 9.0 g/dl; (Note: The use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 9.0 g/dl is acceptable)
- •Total bilirubin < 4 x institutional upper limit of normal (ULN)
- •Transaminases (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) < 6 x institutional ULN
- •Albumin >= 2.5 g/dl
- •Creatinine < 2 mg/dl
- •Prior chemotherapy, targeted biological therapy (e.g. sorafenib), surgery, transarterial chemoembolization (TACE), ablation for present disease is acceptable
- •Must have Child-Turcotte-Pugh (CTP) A or B7
- •The patient or a legally authorized representative must provide study-specific informed consent prior to study registration
排除标准
- •PRIOR TO STEP ONE REGISTRATION:
- •Definitive clinical or radiologic documentation of extrahepatic tumor, defined as extrahepatic metastases or malignant nodes (that enhance with typical features of HCC) > 3.0 cm, in sum of maximal diameters (e.g. presence of one 3.4 cm metastatic lymph node or two 2 cm lung lesions); note that benign non-enhancing periportal lymphadenopathy is not unusual in the presence of hepatitis and is permitted, even if the sum of enlarged nodes is > 2.0 cm
- •Uncontrolled prior invasive malignancy, excluding the current diagnosis
- •Systemic chemotherapy for the study cancer < 2 weeks prior to registration
- •Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic
- •HIV positive with CD4 count < 200 cells/microliter; note that patients who are human immunodeficiency virus (HIV) positive are eligible, provided they are under treatment with highly active antiretroviral therapy (HAART) and have a CD4 count >= 200 cells/microliter prior to registration; note also that HIV testing is not required for eligibility for this protocol; this exclusion criterion is necessary because the treatments involved in this protocol may be significantly immunosuppressive
- •Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields (to include Y90)
- •Prior liver transplant
- •PRIOR TO STEP TWO RANDOMIZATION:
- •Unable to obtain confirmation of payment coverage (insurance or other) for either possible treatment
研究组 & 干预措施
Arm I (proton therapy)
Patients undergo proton therapy over 15-24 days for 5 or 15 fractions. Patients undergo CT scan, MRI and blood sample collection throughout the study.
干预措施: Computed Tomography (Procedure)
Arm I (proton therapy)
Patients undergo proton therapy over 15-24 days for 5 or 15 fractions. Patients undergo CT scan, MRI and blood sample collection throughout the study.
干预措施: Laboratory Biomarker Analysis (Other)
Arm I (proton therapy)
Patients undergo proton therapy over 15-24 days for 5 or 15 fractions. Patients undergo CT scan, MRI and blood sample collection throughout the study.
干预措施: Biospecimen Collection (Procedure)
Arm I (proton therapy)
Patients undergo proton therapy over 15-24 days for 5 or 15 fractions. Patients undergo CT scan, MRI and blood sample collection throughout the study.
干预措施: Quality-of-Life Assessment (Other)
Arm I (proton therapy)
Patients undergo proton therapy over 15-24 days for 5 or 15 fractions. Patients undergo CT scan, MRI and blood sample collection throughout the study.
干预措施: Radiation Therapy (Radiation)
Arm I (proton therapy)
Patients undergo proton therapy over 15-24 days for 5 or 15 fractions. Patients undergo CT scan, MRI and blood sample collection throughout the study.
干预措施: Magnetic Resonance Imaging (Procedure)
Arm II (photon therapy)
Patients undergo photon therapy over 15-24 days for 5 or 15 fractions. Patients undergo CT scan, MRI and blood sample collection throughout the study.
干预措施: Biospecimen Collection (Procedure)
Arm II (photon therapy)
Patients undergo photon therapy over 15-24 days for 5 or 15 fractions. Patients undergo CT scan, MRI and blood sample collection throughout the study.
干预措施: Computed Tomography (Procedure)
Arm II (photon therapy)
Patients undergo photon therapy over 15-24 days for 5 or 15 fractions. Patients undergo CT scan, MRI and blood sample collection throughout the study.
干预措施: Magnetic Resonance Imaging (Procedure)
Arm II (photon therapy)
Patients undergo photon therapy over 15-24 days for 5 or 15 fractions. Patients undergo CT scan, MRI and blood sample collection throughout the study.
干预措施: Quality-of-Life Assessment (Other)
Arm II (photon therapy)
Patients undergo photon therapy over 15-24 days for 5 or 15 fractions. Patients undergo CT scan, MRI and blood sample collection throughout the study.
干预措施: Laboratory Biomarker Analysis (Other)
Arm II (photon therapy)
Patients undergo photon therapy over 15-24 days for 5 or 15 fractions. Patients undergo CT scan, MRI and blood sample collection throughout the study.
干预措施: Radiation Therapy (Radiation)
结局指标
主要结局
Overall survival (OS)
时间窗: From the date of randomization to the date of death due to any cause assessed up to 4 years
Will be estimated by the Kaplan-Meier method. The distributions of OS between treatment arms will be compared using the log rank test. The final analysis will occur after at least 125 deaths have occurred and will include: tabulation of all cases entered and those excluded from the analyses with the reasons for exclusion, distributions of important prognostic baseline variables, the frequencies and severity of adverse events by treatment arm, treatment delivery compliance, observed results with respect to the primary endpoint of OS. Will be tested with a 2-sided significance level of 0.049.
Treatment effect
时间窗: Up to 4 years
Will be performed using the Cox proportional hazard regression model.
次要结局
- Progression-free survival (PFS)(From the date of randomization to the date of first PFS failure or last follow-up for patients without a reported PFS event assessed up to 4 years)
- Local progression (LP)(From the date of randomization to the date of first LP or date of last follow-up for patients without an LP event reported assessed up to 4 years)
- Incidence of adverse events(Up to 4 years)
- Fatigue(Baseline up to 6 months)
- Change in fatigue(Baseline up to 1 month)
- Quality-adjusted survival(Baseline up to 12 months)
- Plasma hepatocyte growth factor (HGF) levels(At baseline)