Pilot-study: Non-thermal Ablation Using Irreversible Electroporation (IRE) to Treat Colorectal Liver Metastases - "Ablate and Resect"
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 10
- 试验地点
- 2
- 主要终点
- Safety
研究概览
简要总结
Irreversible electroporation is a new, minimal-invasive image-guided treatment to treat tumors near or around vulnerable structures, such as central liver tumors.
To investigate the safety and efficacy of IRE in the treatment of colorectal liver metastases, patients with resectable colorectal liver metastases undergo IRE and resection of the metastases in the same session. After resection, the specimen is examined macroscopically to determine vitality using a specific vitality staining (triphenyl-tetrazoliumchloride) and to visualize the exact ablation zone. Subsequently, histopathologic examination is used to determine type of cell death and the microscopic ablation zone.
The investigators hypothesize that IRE is a safe effective method to treat colorectal liver metastasis and that cell damage and cell death is demonstrated as soon as 1 hour after the procedure.
详细描述
This pilot-study is designed to determine the safety of IRE using the NanoKnife on colorectal liver metastases. Secondary, feasibility, histological effect on the ablated cells and exact shape and size of the ablated area will be determined.
Study design:
Patients with resectable CRLM (1 lesion or more) undergoing surgical resection of the metastases will receive study information to participate in this pilot-study. Limited extrahepatic disease is not contra-indicated.
Patients will undergo a general pre-procedural work-up: total body FDG PET-CT, ceCT of the abdomen, anesthetic review with special attention to cardiac history, baseline full blood examination, urea and electrolytes, renal function tests, liver enzymes and coagulation profile test.
The procedure is conducted under general anaesthesia with muscle relaxants to prevent patient motion and epidural analgesia. A laparotomy will be performed at the surgeon's discretion for optimal liver exposure. Intraoperative ultrasonography (IOUS) will be carried out by an experienced interventional radiologist for exact evaluation of maximum diameter, number and location of all lesions and to confirm resectability (if lesions prove not to be resectable, only RFA will be performed according to standard of care). All lesions will be biopsied. The electrodes will be placed under ultrasound guidance according to manufacturer's guidelines in the lesions that are eligible for resection. After correct placement of the electrodes the lesions will be ablated according to protocol with ECG synchronization and the ablation zone is determined by US.
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
- •Liver metastases visible on FDG PET-CT or ceCT, size ≤ 3,5 cm and eligible for resection
- •Resectability re-confirmed per-operatively by US
- •Age > 18 years
- •WHO performance status 0 - 2
- •Life expectancy of at least 12 weeks
- •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 ³ 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
- •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)
- •Uncontrolled infections (> grade 2 NCI-CTC version 3.0).
- •Pregnant or breast-feeding subjects. Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of treatment.
- •Immunotherapy ≤ 6 weeks prior to the procedure
- •Chemotherapy ≤ 12 weeks prior to the procedure
- •Radiotherapy, RFA or MWA treatment of target lesions prior to resection
- •Concomitant use of anti-convulsive and anti-arrhythmic drugs other than beta blockers.
- •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
Safety
时间窗: participants will be followed for the duration of hospital stay, an expected average of 1 week
Safety using Common terminology Criteria for Adverse Events (CTCAE). Since the ablated tissue will be resected we expect procedure-related complications to occur mainly during the procedure.
次要结局
- Efficacy(1 year)
研究者
Dr. M.R. Meijerink
Dr.
Amsterdam UMC, location VUmc