Gene Therapy of Pancreatic Ductal Adenocarcinoma

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.

Inclusion criteria

• 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

Exclusion criteria

• - 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).