COLDFIRE-III Trial: Perivascular and Peribiliary Colorectal Liver Metastases (0-5cm): Irreversible Electroporation Versus Stereotactic Body Radiotherapy
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 78
- 试验地点
- 2
- 主要终点
- Local control
研究概览
简要总结
The primary objective of this phase IIb/III, prospective, randomized clinical trial is to compare the efficacy of irreversible electroporation (IRE) with stereotactic body radiotherapy (SBRT) in patients with perivascular or peribiliary colorectal liver metastases (CRLM), that are not amenable for surgical resection or thermal ablation. Efficacy is assessed in terms of local control at 2 years.
详细描述
Rationale: Currently, the gold standard for perivascular and peribiliary colorectal liver metastases (CRLM), that are not amenable for surgical resection or thermal ablation, is undetermined. Two non-thermal treatment modalities could provide a solution for these anatomically challenging CRLM: irreversible electroporation (IRE) and stereotactic body radiotherapy (SBRT).
IRE is a new, minimal-invasive image-guided treatment method for tumors not amenable for surgical resection or thermal ablation, due to vicinity near vital structures such as vessels and bile ducts. With IRE, multiple electrical pulses are applied to tumorous tissue. These pulses alter the existing transmembrane potential of the cell membranes, and create 'nanopores', after which the cell dies through loss of homeastasis. SBRT is another non-thermal ablation modality and has important advantages over conventional radiotherapy such as a more precise and greater biological dose delivery and hence less toxicity and presumably better outcome.
Study design: The COLDFIRE-III trial is a phase IIB/III, prospective randomized clinical trial. The primary conducting center will be the Amsterdam UMC (Amsterdam, the Netherlands). The purpose of this study is to assess and compare the efficacy of IRE and SBRT for perivascular or peribiliary CRLM in terms of local control at 2 years. Other objectives are overall survival, additional efficacy endpoints, safety, pain assessments and costs. For the sample size calculations, the log-rank test is used. The (2-year survival) proportion in group 1 (a treatment group) is 0.80. The proportion in group 2 (the alternative treatment group) is 0.55. The significance level of the test is 0.10. A total number of 78 patients will be randomized into one of two arms: arm A (IRE, n = 39) and arm B (SBRT, n = 39).
Study population: 78 patients with 1-3 perivascular and peribiliary lesions of 0-5 cm, ineligible for surgical resection and thermal ablation, suitable for both IRE and SBRT and no or limited extrahepatic disease (1 extrahepatic lesion is allowed, not including positive para-aortic lymph nodes, celiac lymph nodes, adrenal metastases, pleural carcinomatosis or peritoneal carcinomatosis) can be included. Supplementary resections for resectable lesions and thermal ablations for unresectable CRLM are allowed. A maximum number of 10 CRLM are allowed for patients with no extrahepatic disease and a maximum number of 5 lesions are allowed for patients with limited extrahepatic disease. Eligible patients will be stratified according to tumor size (≤3cm vs. 3-5 cm) and (induction) chemotherapy prior to local treatment.
Intervention: Patients will be randomized into one of two arms, arm A (IRE) and arm B (SBRT). The expert panel, consisting of at least two interventional radiologists, two radiation oncologists and two hepatobiliary surgeons, will appoint lesions that are ineligible for surgery of thermal ablation, and suitable for both IRE and SBRT, as target lesions.
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
- •Histological documentation of primary colorectal tumor is available;
- •1-3 CRLM visible on ceCT and/or MRI, size 0-5 cm and not eligible for resection or thermal ablation due to location close to a vessel or bile duct;
- •Additional CRLM are allowed if considered either resectable or ablatable with a maximum of 10 CRLM. In patients with extrahepatic disease, a maximum of 5 additional CRLM is allowed;
- •No or limited extrahepatic disease (1 extrahepatic lesion is allowed, with some exclusions mentioned in the
排除标准
- •Prior focal liver treatment is allowed;
- •Subjects should preferably be treated with neo-adjuvant systemic therapy;
- •Subjects with recurrent (either local or distant-hepatic) CRLM after previous focal treatment who are unsuitable for (further) systemic therapy (further downsizing or conversion to resectable disease improbable);
- •Adequate bone marrow, liver and renal function as assessed by laboratory requirements to be conducted within 7 days prior to definite inclusion;
- •ASA classification 0 - 3;
- •Age >18 years;
- •Written informed consent;
- •Exclusion Criteria:
- •Radical treatment unfeasible or unsafe (e.g. insufficient FLR);
- •>10 CRLM; >5 CRLM when extra-hepatic disease is present;
- •Positive para-aortal lymph nodes, celiac lymph nodes, adrenal metastases, pleural carcinomatosis or peritoneal carcinomatosis;
- •Subjects who have progressive disease after neo-adjuvant systemic therapy;
- •History of epilepsy;
- •History of cardiac disease:
- •Uncontrolled hypertension. Blood pressure must be ≤160/95 mmHg at the time of screening on a stable antihypertensive regimen;
- •Compromised liver function (e.g. signs of portal hypertension, INR > 1,5 without use of anticoagulants, ascites);
- •Pregnant or breast-feeding subjects;
- •Immunotherapy ≤ 2 weeks prior to the procedure;
- •Chemotherapy and/or targeted therapy ≤ 2 weeks prior to the procedure;
- •Severe allergy to contrast media not controlled with premedication;
- •Any condition that is unstable or that could jeopardize the safety of the subject and their compliance in the study.
结局指标
主要结局
Local control
时间窗: 2 years
Local control is defined as no objectified signs for local tumor progression on imaging acquired 23-24 months following start of the initial study procedure, according to the RECIST criteria. Site recurrences within the first 12 months that are successfully retreated once using the same technique (re-IRE or re-SBRT), thermal ablation or surgical resection will not be regarded as an event for local control. Per patient analysis.
次要结局
- Safety per procedure and per patient(Assessed up to 5 years)
- Cost-effectiveness ratio (ICER) per patient(Assessed up to 5 years)
- Overall survival (OS) per patient(Assessed up to 5 years)
- Local tumor progression-free survival (LTPFS) per patient and per tumor.(Assessed up to 5 years)
- Distant tumor progression-free survival (DPFS) per patient(Assessed up to 5 years)
- Time to progression (TTP) per patient(Assessed up to 5 years)
- Quality of life (QoL) per patient as assessed by EORCT QLQ-C30 questionnaires(Assessed up to 1 year)
- Quality of life (QoL) per patient as assessed by EQ-5D questionnaires(Assessed up to 1 year)
- Quality of life (QoL) per patient as assessed by PRODISQ questionnaires(Assessed up to 1 year)
- Assessment of pain per patient(Assessed up to 1 year)
研究者
M.R. Meijerink
Prof. dr.
Amsterdam UMC, location VUmc