IRE: Anti-Tumor Immunity Induced by IRE of Unresectable Pancreatic Cancer
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Characterization of the intra-tumoral and systemic immune response to IRE in unresectable pancreatic cancers
研究概览
简要总结
This protocol will study the impact of Irreversible electroporation (IRE) on immune response in patients diagnosed with unresectable pancreatic cancers smaller than 5.0 cm. It will profile the immune response to IRE of unresectable pancreatic cancers. The intra-tumoral and systemic immune response to IRE will be determined and compared to pre-ablated pancreatic cancer specimens and historical control specimens.
详细描述
Thirty patients with histologically confirmed locally advanced pancreatic adenocarcinoma (≤5.0cm) will undergo percutaneous irreversible electroporation of the tumor using CT and ultrasound guidance. Blood will be drawn for research before IRE. Blood and tissue samples will be used.
After IRE, patients will be carefully monitored and systemic immune responses are registered. Follow-up will consist of frequent CT and MRI scanning, as well as serum CA19.9 tumor marker and quality of life questionnaires and overall survival (OS).
The investigators hypothesize that IRE in the pancreas will induce good symptom palliation without causing severe complications as well as perfect systemic immune response.
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
- Single (Investigator)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Radiologic confirmation of unresectable pancreatic cancer by at least CT of chest and abdomen
- •Screening must be performed no longer than 2 weeks prior to study inclusion
- •Maximum tumor diameter ≤ 5 cm;
- •Histological or cytological confirmation of pancreatic adenocarcinoma;
- •Age ≥ 18 years;
- •ASA-classification 0 - 3
- •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 ≥ 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
- •Resectable pancreatic adenocarcinoma as discussed by our multidisciplinary hepatobiliary team;
- •Successful down staging after (radio)chemotherapy from previous unresectable/borderline tumor to resectable tumor;
- •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 for antihypertensive regimen 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. 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 ≤ 6 weeks prior to the procedure;
- •Radiotherapy ≤ 6 weeks prior to the procedure;
- •Concomitant use of anti-convulsive and anti-arrhythmic drugs (other than beta blockers used for antihypertensive);
- •Allergy to contrast media;
- •Any implanted stimulation device;
- •Any implanted metal stent/device within the area of ablation that cannot be removed;
- •Any condition that is unstable or that could jeopardize the safety of the subject and their compliance in the study; Of note, patients with contra-indications for MRI will not be excluded from participation: in this case radiologic follow-up will consist of CT-scanning according to protocol.
研究组 & 干预措施
NanoKnife LEDC System
90 pulses of 70 microseconds each in duration will be administered per electrode pair.
干预措施: NanoKnife LEDC System (Device)
Control
The patients without treatment
结局指标
主要结局
Characterization of the intra-tumoral and systemic immune response to IRE in unresectable pancreatic cancers
时间窗: 12 Months
1. Determine number (percentage via flow cytometry), phenotype and functionality of tumor infiltrating lymphocytes in ablated pancreatic cancer 2. Determine morphology and histology of regional lymph node after IRE 3. Quantify T cell response (IUs of IL2 and IFN gamma, and T cell specific cells as measured by number of spots on an elispot assay) to tumor associated antigens using in vitro assays of T cell proliferation and function (cytokine release, elispot, peptide-MHC)
次要结局
- Comparison immune response between non-ablated and ablated pancreatic cancer and pre-ablated and post ablated serum(24 Months)