gene therapy of pancreatic ductal adenocarcinoma

Conditions: Pancreatic Adenocarcinoma

Summary: 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.

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.

Eligibility criteria:
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).

Keywords: gene therapy pancreatic carcinoma gemcitabine endoscopic ultrasound