NCT04835402进行中（未招募）2 期
A Phase II Study of Electroporation Potentiated Immunotherapy in Liver Metastatic
Ole Thorlacius-Ussing, MD, DMSc, Professor of Surgery1 个研究点 分布在 1 个国家目标入组 8 人开始时间: 2021年5月26日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 8
- 试验地点
- 1
- 主要终点
- Serious adverse reaction (SAR) rate according to CTCAE v5
研究概览
简要总结
The study is investigating the efficacy and safety of combined irreversible electroporation (IRE) and checkpoint inhibition in metastatic pancreatic cancer.
详细描述
The aim of the study is to investigate whether checkpoint inhibition in conjunction with IRE of a single liver metastasis can elicit a systemic anticancer immune response in patients with pancreatic cancer.
Adult patients, in WHO performance status 0-1, with liver metastatic pancreatic cancer, intolerant to or progressing on first or further lines of chemotherapy can enter the trial. Pembrolizumab infusion is given every six weeks for up to six months. IRE of a single liver metastasis is performed between the first and second pembrolizumab infusion.
Response to the therapy is examined by CT (RECIST) on non-IRE-ablated lesions every 2 months. Assessments of changes in peripheral blood immune cell composition, tumor gene expression and tumor infiltrating lymphocytes is performed on serial biopsies and blood samples.
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
- •Histologically verified pancreatic adenocarcinoma, based on either a biopsy of the primary tumor or a metastasis
- •One liver metastasis treatable by IRE (as determined by MDT at Aalborg University Hospital)
- •One tumor lesion suited for repeated biopsy by transcutaneous core needle (preferably another lesion than that used for IRE)
- •At least one measurable lesion (RECIST version 1.1) other than the liver metastasis to be treated by IRE
- •At least one course of chemotherapy for metastatic or inoperable disease discontinued due to treatment failure or intolerance
- •Performance status 0-1
- •≥ 18 years of age
- •Written and orally informed consent
- •Sufficient available histological tumor material stored in biobank or obtainable by new biopsy
- •Patient acceptance of collection of blood samples for translational research and two additional biopsies during treatment
- •Adequate bone marrow function, liver function, and renal function (within 7 days prior to enrollment):
- •Neutrophils (ANC) ≥ 1.5 x 109/l
- •Platelet count ≥ 100 x 109/l
- •Hemoglobin ≥ 6 mmol/l
- •Plasma bilirubin ≤ 1.5 x ULN
- •Plasma alanine transaminase (ALAT) < 5 x ULN
- •Plasma creatinine ≤ 1.5 x ULN
排除标准
- •Underlying medical disease not adequately treated (e.g. poorly regulated diabetes and symptomatic cardiac disease)
- •Prior or current autoimmune disorder with risk of serious toxicity during treatment with checkpoint inhibitor
- •Acute myocardial infarction, cerebral vascular attack, transient ischemic attack or subarachnoid hemorrhage within 6 months from start of treatment
- •Previous reception of allogeneic stem cells or solid organ donation
- •Active infection requiring systemic therapy within 7 days prior to treatment initiation
- •Positive HIV, HBV, and HCV test results (prior testing or new testing in patients at risk)
- •Active psychiatric disease or history of drug or alcohol abuse affecting participation
- •Allergy to active substance or any of the auxiliary agents, including known severe allergy to anesthetic agent, paralytic agent or any of the equipment used during treatment
- •Expected need for systemic corticosteroid or other systemic immunosuppressive drug during the course of this clinical trial. A low dose of e.g. prednisone ≤ 10 mg/day is permitted for maximally 7 consecutive days
- •Coexisting malignant disease, except non-melanoma skin cancer
- •Symptomatic or untreated CNS metastases
- •Liver cirrhosis Child Pugh >A
- •Pregnant or breast-feeding patients. For women of childbearing potential, a negative pregnancy test (minimum sensitivity 25mIU(hCG)/ml) is mandatory prior to inclusion and every month during the trial
- •Women of childbearing potential not willing to use effective methods of contraception during treatment and for 6 months after the end of treatment. Male patients with a fertile partner are also required to secure effective methods of contraception (definition available in protocol)
- •Previous immunotherapy
- •Patients referred from a hospital outside of Denmark
- •Major dilation of veins or bowel obstructing the needle path
- •Persistent atrial fibrillation
- •Metal objects (e.g. biliary SEMS) within 5 cm of ablation target
- •Cardiac pacemaker or ICD, that cannot be safely disconnected during IRE treatment
研究组 & 干预措施
Intervention
Experimental
Day 1: Pembrolizumab 400mg Day 10: Irreversible electroporation Day 42/84/126/168: Pembrolizumab 400mg
干预措施: Pembrolizumab (Drug)
Intervention
Experimental
Day 1: Pembrolizumab 400mg Day 10: Irreversible electroporation Day 42/84/126/168: Pembrolizumab 400mg
干预措施: Irreversible electroporation (Device)
结局指标
主要结局
Serious adverse reaction (SAR) rate according to CTCAE v5
时间窗: cumulative after 12 months after treatment start
(in patients receiving at least one dose of pembrolizumab)
Objective response rate (ORR) according to RECIST 1.1
时间窗: 6 months after treatment start
(in patients receiving at least one dose of pembrolizumab, IRE and an evaluable CT-scan)
次要结局
- Median overall survival(Through study completion, an average of 1 year)
- Survival rate(6 months and 12 months after treatment start)
- Median progression-free survival(Through study completion, an average of 1 year)
- Progression-free survival rate(6 months and 12 months after treatment start)
- Clinical benefit ratio(8 weeks after treatment start)
- Difference in peripheral blood myeloid-derived suppressor cell count prior to IRE-treatment, 1 day after IRE-treatment and 6 weeks after IRE-treatment compared to baseline(8 days, 11 days, 52 days after treatment start)
- ORR(2 months, 4 months and 6 months after treatment start)
- Difference in peripheral blood naïve T cell count prior to IRE-treatment, 1 day after IRE-treatment and 6 weeks after IRE-treatment compared to baseline(8 days, 11 days, 52 days after treatment start)
- Difference in peripheral blood exhausted T cell count prior to IRE-treatment, 1 day after IRE-treatment and 6 weeks after IRE-treatment compared to baseline(8 days, 11 days, 52 days after treatment start)
- Difference in tumor RNA expression after pembrolizumab and after pembrolizumab + IRE compared to baseline(10 days and 52 days after treatment start)
- Adverse event rate (CTCAEv5, all grades)(cumulative after 12 months after treatment start)
- Difference in peripheral blood central memory T cell count prior to IRE-treatment, 1 day after IRE-treatment and 6 weeks after IRE-treatment compared to baseline(8 days, 11 days, 52 days after treatment start)
- Difference in peripheral blood terminally differentiated effector T cell count prior to IRE-treatment, 1 day after IRE-treatment and 6 weeks after IRE-treatment compared to baseline(8 days, 11 days, 52 days after treatment start)
- Histological tumor regression grade in tumor biopsies after pembrolizumab and after pembrolizumab + IRE compared to baseline(10 days and 52 days after treatment start)
- Serum CA-19-9 response(2 months, 4 months and 6 months after treatment start)
- Mean difference in perceived quality of life measured by EORTC QLQ-C30 v3(2 months, 4 months, 6 months, 8 months, 10 months and 12 months after treatment start)
- Mean difference in nutrition status measured by PG-SGA-SF(2 months, 4 months, 6 months, 8 months, 10 months and 12 months after treatment start)
- Difference in peripheral blood effector memory T cell count prior to IRE-treatment, 1 day after IRE-treatment and 6 weeks after IRE-treatment compared to baseline(8 days, 11 days, 52 days after treatment start)
- Difference in (histological) tumor infiltrating leukocyte (TIL) pattern after pembrolizumab and after pembrolizumab + IRE compared to baseline(10 days and 52 days after treatment start)
- Difference in peripheral blood effector T cell count prior to IRE-treatment, 1 day after IRE-treatment and 6 weeks after IRE-treatment compared to baseline(8 days, 11 days, 52 days after treatment start)
- Difference in peripheral blood regulatory T cell count prior to IRE-treatment, 1 day after IRE-treatment and 6 weeks after IRE-treatment compared to baseline(8 days, 11 days, 52 days after treatment start)
- Difference in peripheral blood conventional dendritic cell type 1 count prior to IRE-treatment, 1 day after IRE-treatment and 6 weeks after IRE-treatment compared to baseline(8 days, 11 days, 52 days after treatment start)
- Difference in peripheral blood conventional dendritic cell type 2 count prior to IRE-treatment, 1 day after IRE-treatment and 6 weeks after IRE-treatment compared to baseline(8 days, 11 days, 52 days after treatment start)
- Difference in peripheral blood plasmacytoid dendritic cell count prior to IRE-treatment, 1 day after IRE-treatment and 6 weeks after IRE-treatment compared to baseline(8 days, 11 days, 52 days after treatment start)
研究者
Ole Thorlacius-Ussing, MD, DMSc, Professor of Surgery
Professor of surgery, Consultant surgeon, DMSc
Aalborg University Hospital
研究点 (1)
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