Gene Electrotransfer to Muscle With Plasmid AMEP in Patients With Disseminated Cancer
2014年6月19日 更新者：Copenhagen University Hospital at Herlev
Gene transfer by electroporation (gene electrotransfer) uses short electric pulses to transiently permeabilise the cell membrane enabling passage of plasmid DNA into the cell cytosol.
It is an efficient non-viral method for gene delivery to various tissues.
In this phase I dose-escalating study, patients will be treated with intramuscular gene electrotransfer of plasmid AMEP.
Plasmid AMEP encodes protein AMEP which bind to α5β1 og αvβ3 integrins.
Primary end point of the trial is safety and secondary end points are efficacy, pharmacokinetics and evaluation of potential discomfort associated with the treatment procedure using VAS (Visual Analogue Scale).
研究概览
详细说明
Cohorts of 3 patients will be treated with increasing doses of plasmid AMEP. Up to 12 patients will be treated.
Treatment procedure: Local anesthetic is applied to m. quadriceps femoris (thigh muscle) and the skin. An incision of the skin is performed followed by dissection until the muscle is exposed. The surgical procedure is performed by plastic surgeons.
Plasmid AMEP is injected intramuscularly and immediately followed by application of electric pulses via a needle electrode inserted into the muscle. A combination of one high voltage pulse (700V/cm, 100 µs) followed by one low voltage pulse (80 V/cm, 400 ms) will be applied. The wound is sutured and a dressing is applied. Treatment procedure is estimated to 30 minutes.
All patients are hospitalized for 24 hours after treatment for the purpose of evaluation of vital signs, physical examination, AE and SAE recording and pharmacokinetics sampling (blood and urine).
Blood biochemistry including LDH and CK is taken 24 hours post treatment. ECG will be taken before and after treatment. Patients score discomfort or pain from treated area using VAS.
研究类型
介入性
注册 (实际的)
7
阶段
- 阶段1
联系人和位置
本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。
学习地点
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Herlev、丹麦、2730
- Depart. of Oncology, Copenhagen Universtiy Hospital Herlev
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参与标准
研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
18年 及以上 (成人、年长者)
接受健康志愿者
不
有资格学习的性别
全部
描述
Inclusion Criteria:
- Age > 18 years.
- Performance status < 1 (ECOG).
- Histologically confirmed malignant tumor (solid tumor) of any histology,
- Metastatic disease. Patients with asymptomatic brain metastases are eligible.
- Patient should have been offered standard treatment. Patient is eligible if no standard treatment is available or if the patient does not wish to receive standard treatment.
- Life expectancy ≥ 3 months.
- Measurable disease defined as at least one measurable lesion according to RECIST 1.1
- Patient should have adequate organ function:
- Adequate bone marrow function: Neutrophil count ≥ 1.0 x 109/l (≤ grade 2 CTCAE 4.0); Platelet count ≥ 75 x 109/l (< grade 2 CTCAE 4.0); Hemoglobin ≥ 6,0 mmol/l.
- Liver: ALAT or ASAT < 3 ULN (< grade 2 CTCAE 4.0); Bilirubin ≤ 1,5 ULN (< grade 2 CTCAE 4.0); APTT within normal range; INR ≤ 1,2 (< grade 1 CTCAE 4.0)
- Kidney: Plasma creatinin ≤ 1.5 ULN (< grade 2 CTCAE 4.0)
- At least 4 weeks since any anti-cancer treatment.
- Men and women of reproductive age must use effective contraception during the study and at least 6 months after administration of plasmid AMEP.
- Patient should be able to understand the participant information and able to comply with protocol requirements and scheduled visits.
- Signed informed consent.
Exclusion Criteria:
- Allergy to the anaesthetic used.
- Clinical signs of active infection.
- Implanted pacemaker, defibrillator or any other implanted electronic device.
- Participation in other clinical trials involving experimental drugs or participation in a clinical trial within 4 weeks before initiation of study treatment.
- AMI (acute myocardial infarction), stroke or acute ischemic event within the last 6 months.
- Severe atherosclerosis, significant cardiovascular disease (NYHA III or IV) or significant arrhythmias.
- Systolic blood pressure above 180 mm Hg and/or diastolic blood pressure above 110 mm Hg. If BP >180/110 mm Hg medical correction is allowed and the patient can be included when BP < 180/110 mm Hg.
- Pregnancy and lactation.
- Clinically significant coagulopathy.
- Treatment with anticoagulant drugs.
- Other disorders which the investigator finds incompatible with participation in the study.
学习计划
本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：不适用
- 介入模型：单组作业
- 屏蔽：无（打开标签）
研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Safety of the trial treatment
大体时间：From treatment to last follow up, planned 8 weeks.
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Safety is evaluated by registration of adverse events (Adverse Events and Serious Adverse Events) using the CTCAE criteria version 4.0.
Patients are seen in the out patient clinic once a week during the first month after treatment (at day 8, day 15, day 22, day 29) and 8 weeks after treatment.
If no progression of the disease at 8 weeks, patients are seen at 12 weeks and then every three months until disease progression or death.
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From treatment to last follow up, planned 8 weeks.
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Efficacy of the trial treatment
大体时间：PET/CT scan 4 weeks, 8 weeks and 12 weeks after trial treatment.
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PET/CT scan will be evaluated using RECIST 1.1 (CT) and PERCIST (PET)
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PET/CT scan 4 weeks, 8 weeks and 12 weeks after trial treatment.
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Pharmacokinetics
大体时间：Pre-dose, 2, 6 and 24 hours after dose, day 8, 15, 22, 29 and 8 weeks after treatment.
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Measurements of plasma and urine plasmid AMEP concentrations.
Measurements of plasma and urine protein AMEP concentrations
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Pre-dose, 2, 6 and 24 hours after dose, day 8, 15, 22, 29 and 8 weeks after treatment.
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Discomfort associated with the treatment procedure
大体时间：Scoring 'immediately after treatment', '30 min after treatment' '6 hours after treatment' and 'pain in the past 24 hours', and day 8.
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The patient completes VAS (Visual Analogue Scale) scores pain related to the treatment area at abovementioned time points.
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Scoring 'immediately after treatment', '30 min after treatment' '6 hours after treatment' and 'pain in the past 24 hours', and day 8.
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Safety
大体时间：Day after treatment and 14 days after treatment
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MR scan of treated region (thigh muscle) in order to assess potential intramuscular edema or hematoma
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Day after treatment and 14 days after treatment
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合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
调查人员
- 首席研究员：Julie Gehl, MD DMSci、Department of Oncology, Copenhagen University Hospital Herlev
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始
2012年7月1日
初级完成 (预期的)
2015年5月1日
研究完成 (预期的)
2015年5月1日
研究注册日期
首次提交
2012年7月16日
首先提交符合 QC 标准的
2012年8月10日
首次发布 (估计)
2012年8月14日
研究记录更新
最后更新发布 (估计)
2014年6月20日
上次提交的符合 QC 标准的更新
2014年6月19日
最后验证
2014年6月1日
更多信息
与本研究相关的术语
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.