PILOT STUDY OF GENE THERAPY FOR LOCALLY ADVANCED PANCREATIC ADENOCARCINOMA WITH INTRATUMOURAL INJECTION OF JetPEI/DNA COMPLEXES WITH ANTITUMOURAL EFFECT AND CHEMOSENSITIZING ACTIVITY FOR GEMCITABINE
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 22
- 试验地点
- 2
- 主要终点
- Feasability and security : Number of Participants with Adverse Events
研究概览
简要总结
Near 85% of patients with pancreatic adenocarcinoma are diagnosed with a locally advanced and/or metastatic unresectable tumor. In these patients chemotherapy (such as gemcitabine) is given as a palliative therapy. Aim of the present study is to evaluate the feasibility, tolerance and antitumor effect of repeated intratumoral injection of a gene therapy product (with antitumor and chemo sensitizing effects) combined with gemcitabine in patients with unresectable pancreatic carcinoma.
详细描述
This is a gene therapy open non randomized phase I trial for advanced and/or metastatic pancreatic cancer patients. The protocol is based on the administration of increasing doses of a plasmid DNA pre-complexed to PEI (polyethylenimine - non-viral vector) that encodes two genes (somatostatin receptor subtype 2 named sst2 and deoxycitidine kinase :: uridylmonophosphate kinase named dck::umk) which exhibit complementary therapeutic effects. Both transgenes induce an antitumor bystander effect and render gemcitabine treatment more efficient. Intratumor injections of the gene therapy product (CYL-02) will be performed by transgastric or transduodenal route under endoscopic ultrasound guidance. Each injection will be followed standard gemcitabine IV administration every week (1000 mg/m2). Two intratumor injections of a same dose of CYL-02 will be administered at one month interval. Four increasing doses (125 µg, 250 µg, 500 µg and 1 mg) will be tested by group of 6 patients. The primary objectives are: evaluation of local pancreatic and general tolerance; the secondary objectives are: possible tumor volume regression, secondary respectability, evaluation of transgene biodistribution.
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
- •Patient with a pancreatic adenocarcinoma histologically proven and/or a solid pancreatic mass associated with on or multiple metastatis from pancreatic origin (histologically proven)
- •Patient with a non resectable pancreatic adenocarcinoma (on preoperative CT-scan and/or endoscopic ultrasound evaluation)
- •Pancreatic tumor that could be evaluated by endoscopic ultrasound (no digestive stenosis, no gastrectomy)
- •Patient with no contraindication to général anaesthesia.
- •Karnofsky index >= 70%
- •Written informed consent given
排除标准
- •- Exclusion period for another clinical trial or research protocol.
- •Patient unable to read or understand information/consent formula or unable to decide alone for his participation to the trial
- •Patient under tutelage
- •Pregnant woman or able to procreate without contraception.
- •Patient with pancreatic cystic tumor or pancreatic pseudocyst.
- •Patient with pancreatic tumor different from adenocarcinoma (endocrine, metastasis).
- •Patient contraindication to Gemzar® :
- •Hypersensitivity to Gemcitabine.
- •Decision of radiotherapy
- •Granulocytes < 1000/mm3
- •Thrombocytes < 100 000/mm3
- •Patient not efficiently treated for jaundice (biliary stent or bypass) if present at time of diagnosis
- •Contraindication for fine needle aspiration biopsy under endoscopic ultrasound (hemostasis trouble).
结局指标
主要结局
Feasability and security : Number of Participants with Adverse Events
时间窗: 60 days
Feasibility, security (pancreas and general) of intratumor injections of the gene therapy product (CYL-02 plasmid DNA pre-complexed to PEI encoding sst2 dck::umk) administered under endoscopic ultrasound guidance and followed by gemcitabine treatment at standard doses.
次要结局
- Antitumoral effect: secondary resecability, transgenes diffusion(60 days)