Colorectal Metastatic Liver Disease: Efficacy of Irreversible Electroporation (IRE) - a Phase II Clinical Trial (COLDFIRE-2 Study)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 51
- 试验地点
- 6
- 主要终点
- Efficacy
研究概览
简要总结
Irreversible electroporation (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.
The purpose of this study is to investigate the efficacy of percutaneous and open IRE in the treatment of patients with colorectal liver metastases (CRLM) that are unsuitable for resection or thermal ablation due to vicinity to vulnerable structures such as vessels and bile ducts. Other objectives are safety, feasibility (technical success) and imaging characteristics on follow-up (PET-)CT and PET-MRI and the value of these imaging modalities in dianosing local site recurrence (LSR) or residual disease (RD).
29 patients with histologically confirmed colorectal carcinoma who present with unresectable and not thermally ablative CRLM< 3.5cm suitable for IRE will undergo percutaneous or open irreversible electroporation of the tumor using CT and ultrasound guidance. All (serious) adverse events are registered. One day post-IRE MRI is performed to assess technical success. Follow-up will consist of frequent (PET-)CT and (PET-)MRI scanning to localize residual or recurrent disease. Overall technique effectiveness is determined 1 year after treatment.
The investigators hypothesize that IRE for central CRLM will lead to good tumor control without causing severe complications.
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
- •Histological or cytological documentation of primary colorectal tumor;
- •Previous induction chemotherapy due to unresectability; no intra- or extrahepatic disease progression under induction chemotherapy; OR
- •Previous chemotherapy for other CRLM, now presenting with renewed CRLM unsuitable for resection or thermal ablation;
- •Liver metastases F-18-FDG PET avid and visible on ceCT, size ≤ 3,5 cm and not eligible for resection or thermal ablation due to location close to a vessel or bile duct;
- •Age more than 18 years;
- •ASA classification 0 - 3;
- •Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to definite inclusion:
- •Hemoglobin ≥ 5.6 mmol/L;
- •Absolute neutrophil count (ANC) ≥ 1,500/mm3;
- •Platelet count ≥ 100*109/l;
- •Total bilirubin ≤ 1.5 times the upper limit of normal (ULN);
- •ALT and AST ≤ 2.5 x ULN
- •Serum creatinine ≤ 1.5 x ULN or a calculated creatinine clearance > 50 ml/min;
- •Prothrombin time or INR < 1.5 x ULN;
- •Activated partial thromboplastin time < 1.25 x ULN (therapeutic anticoagulation therapy is allowed if this treatment can be interrupted as judged by the treating physician)
- •Written informed consent
排除标准
- •Lesion > 3,5 cm size;
- •History of epilepsy;
- •Extrahepatic metastases rendering local therapy unfeasible;
- •History of cardiac disease:
- •Congestive heart failure >NYHA class 2;
- •Active Coronary Artery Disease (defined as myocardial infarction within 6 months prior to screening);
- •Cardiac arrhythmias requiring anti-arrhythmic therapy or pacemaker (beta blockers are permitted);
- •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 ≤ 6 weeks prior to the procedure;
- •Chemotherapy ≤ 6 weeks prior to the procedure;
- •Concomitant use of anti-convulsives and anti-arrhythmic drugs other than beta blockers for antiepileptic or antiarrhythmic purpose;
- •Allergy to contrast media;
- •Any implanted stimulation device;
- •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
Efficacy
时间窗: 12 months
The primary objective of this project is to evaluate the efficacy (percentage of lesions that show no sign of recurrence 12 months after the initail IRE procedure) of IRE for CRLM on cross-sectional imaging performed after respectively 6 weeks, and after 3, 6, 9 and 12 months. Research has shown that 95% of all recurrences after RFA of CRLM are diagnosed within one year after treatment. Therefore, one year follow-up will allow for accurate calculation of efficacy. Exact secondary efficacy rate may require follow-up longer than 12 months since this includes lesions that have been re-treated due to local site recurrence/local tumor residue (which will be individualized for each patient after re-treatment of LSR/LTR).
次要结局
未报告次要终点
研究者
Dr. M.R. Meijerink
Dr.
Amsterdam UMC, location VUmc