NCT05435053终止2 期
Irreversible Electroporation in Combination With Immune Checkpoint Inhibition, in Patients With Metastatic Pancreatic Cancer - A Prospective, Phase 2 Study
Ismail Gögenur1 个研究点 分布在 1 个国家目标入组 9 人开始时间: 2022年9月8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
- 终止
- 发起方
- 入组人数
- 9
- 试验地点
- 1
- 主要终点
- Incidence of treatment related adverse events [Safety and Tolerability]
研究概览
简要总结
The trial investigates the safety and efficacy of irreversible electroporation in combination with checkpoint inhibition in patients with metastatic pancreatic cancer.
详细描述
The trial is designed as an investigator initiated prospective phase 2 study in patients with metastatic pancreatic cancer (PC) to determine the efficacy and safety of checkpoint inhibition administered concurrently with irreversible electroporation.
A recently published preclinical study by Zhao et al. (2019) showed that the combination of IRE and PD-1-inhibitor suppressed the tumour growth and increased the survival of mice bearing pancreatic cancer.
The aim of the trial is to initiate an abscopal response, leveraging the patient's immune system in eliciting a sufficient immune response.
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 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent.
- •Histopathological confirmation of pancreatic adenocarcinoma.
- •At least one measurable primary in-situ (or locally-recurrent) or metastatic tumor must be present and, in the opinion of the investigators be amenable to IRE, and at least one additional metastatic tumor that will not undergo IRE. Both lesions must be accessible for image-guided percutaneous biopsy.
- •Age > 18 years
- •Life expectancy greater than 3 months
- •ECOG (Eastern Cooperative Oncology Group) Performance Status (PS) 0-1
- •Patients must have normal organ and marrow function as defined below:
- •White blood cell count (WBC) ≥ 2 x 10⁹/L
- •Absolute neutrophil count (ANC) ≥ 1.5 x 10⁹/L
- •Hemoglobin ≥ 5,6 mmol/l
- •Platelet count ≥ 100 x 10⁹/L
- •Serum bilirubin ≤1.5 x upper limit of normal (ULN) (patients with Gilbert's Syndrome must have a total bilirubin ≤ 50 mmol/L )
- •ASAT/ALAT ≤3 x ULN ( < 5 x ULN if known liver metastasis)
- •PP ≥ 40 or INR ≤ 1.5
- •Serum creatinine ≤ 1.5 x ULN or eGFR ≥ 40 mL/min
- •Women of childbearing potential (WOCBP) must use method(s) of contraception as indicated per protocol.
- •WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of nivolumab.
- •Women must not be breastfeeding
- •Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year.
- •Men who are sexually active with WOCBP must continue contraception for 31 weeks (90 days plus the time required for nivolumab to undergo five half-lives) after the last dose of investigational drug.
排除标准
- •Malignant ascites that is clinically detectable by physical examination or is symptomatic.
- •Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T cell co-stimulation or checkpoint pathways
- •Radiotherapy, or major surgery within the last 2 weeks prior to entering the study
- •Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results.
- •Patients should be excluded if they have an active, known or suspected autoimmune disease.
- •Patients should be excluded if they are positive test for hepatitis B virus surface anti-gen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection
- •Patients should be excluded if they have a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immuno-suppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
- •PD-1 inhibitors may cause hepatic toxicity which may lead to caution regarding other potentially hepatotoxic drugs.
- •Allergies and Adverse Drug Reaction
- •History of allergy to study drug components
- •History of severe hypersensitivity reaction to any monoclonal antibody
- •Patients are excluded if they have active brain metastases or leptomeningeal metastases. Subjects with brain metastases are eligible if metastases have been treated and there is no magnetic resonance imaging (MRI) evidence of progression for [lowest minimum is 4 weeks or more] after treatment is complete and within 28 days prior to the first dose of nivolumab administration. There must also be no requirement for immunosuppressive doses of systemic corticosteroids (> 10 mg/day prednisone equivalents) for at least 2 weeks prior to study drug administration
- •Contraindications for IRE:
- •Implanted pacemaker or ICD (Implantable cardioverter defibrillator) unit.
- •History of epilepsy
- •History of cardiac arrhythmia
- •Recent myocardial infarction
研究组 & 干预措施
IRE + Nivolumab
Experimental
IRE on Day 1, followed by Nivolumab on Day 2/3 and then every 2 weeks (q2w) for a maximum of 24 weeks.
干预措施: Nivolumab (Drug)
IRE + Nivolumab
Experimental
IRE on Day 1, followed by Nivolumab on Day 2/3 and then every 2 weeks (q2w) for a maximum of 24 weeks.
干预措施: Irreversible electroporation (IRE) (Device)
结局指标
主要结局
Incidence of treatment related adverse events [Safety and Tolerability]
时间窗: 6 months after start of treatment
Determined by the incidence and severity of treatment related adverse events according to CTCAE version 4.0
次要结局
- Quality of life using EORTC QLQ-C30(Baseline compared to 14 days, 3 and 6 months after start of treatment)
- Overall survival(From start of treatment until unequivocal disease progression, assessed up to 5 years)
- Tumor response by ultrasound(Baseline compared to 3 and 6 months after start of treatment)
- Progression free survival(From start of treatment until unequivocal disease progression, assessed up to 5 years)
- Tumor response by CT(Baseline compared to 3 and 6 months after start of treatment)
研究者
Ismail Gögenur
Professor
Zealand University Hospital
研究点 (1)
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